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Viral inactivation study is one of the most important aspects of clinical trials, to manufacture and commercialize the biopharmaceutical products derived from human and animal sources. Biologics products that are developed from human, plants and animal resources represents the higher risk levels for viral contamination as these sources are said to carry several human and other pathogenic viruses. Viral contamination of these biologic products used to treat a variety of disease can have several implications from severe clinical complications to economic loss. Viral inactivation method is an important and mandatory step in the process of manufacturing of biological products for removing or inactivating potential contaminant viruses. These biological products are used to treat and diagnose in humans. Viral inactivation testing is necessary for investigational new drug (IND) submission by regulatory authorities and is mainly critical in the development process for biologicals such as tissue and tissue products, stem cell products, blood and blood products, cellular and gene therapy products, and vaccine and therapeutics. The main drivers for the market include rapid growth in pharmaceutical and biotechnology industries and strong R&D investments trend in the life sciences industry. Increase in the number of new drug launches, rise in chronic disease burden, an increase in government support for the pharmaceutical and biotechnology industries will also aid for the growth of the market. For instance, Virosart® Max developed by Sartorius AG is the platform virus prefilter of choice. This virus prefilter protects whatever virus filter you choose irrespective of process conditions. Virosart® Max will downsize your process and reduce your total virus filtration costs. A strong pharmaceutical product pipeline will aid the growth of the pharmaceutical and biotechnology industry, which is an important end-user of viral inactivation products. The introduction of many new drugs into the market has necessitated the testing of these drugs and has created demand within the global viral inactivation market. The bio-similar products and biologics field has undergone rapid advancements in recent times that have furthered the global viral inactivation market growth. A wide range of instruments is used in the viral inactivation process. For instance, FlexAct VI is considered a single-use technology developed by Sartorius AG, which allows virus inactivation by using low pH. This device is designed in a way for addressing the production capacity and tailored to adjust features like pH, temperature, pump speed, pressure, and fluid level. The biopharmaceutical industry attracted the attention of several governments, organizations, and international entities, and the need for developing this industry has become a need across the globe. This is expected to be a huge plus for the global viral inactivation market and is projected to reap tremendous revenues into the market over the forthcoming years. Further, the smaller market players are expected to stick to the basics and are learning from the footsteps of their developed counterparts. Thus, it is safe to prognosticate that the market players in the global viral inactivation market can see the emergence of several new growth opportunities over the forthcoming years. For instance, Parker Hannifin Corporation announced the acquisition of SciLog Inc, which is a provider of proprietary and unique single-use technologies and systems for biopharmaceutical markets for supporting their on-going development, which is a key supplier to the growing single-use market. The high degree of market consolidation is a major factor restraining the growth of this market. Despite the growth of the global market for viral inactivation, the high costs that are associated with the manufacturing of biosimilar products are expected to restrain the market growth. Further, the discovery of new types of viruses that cannot be countered with the current forms of vaccinations has also proved to a roadblock for the growth of the global viral inactivation market. Nevertheless, the rising incidence of contagious diseases and an outburst of viral infections are expected to keep bolstering demand within the global market. Furthermore, the rising geriatric population that is frequently in need of biologic therapeutics is also an advantage for vendors in the global viral inactivation market. The global viral inactivation market is segmented on method, product, application, end user, and geography. By Method: Solvent detergent method, Alkylating agent, Pasteurization, and other methods. Other viral inactivation method includes low pH, microwave heating, irradiation, and high-energy light. Of these, the solvent detergent method segment accounted for the largest share of the global viral inactivation market. By Product: Kits and reagents, Services, and viral inactivation systems and accessories. Kits and reagents are projected to account for the largest market share in the global viral inactivation market owing to their continuous usage by pharmaceutical and biopharmaceutical companies. Services are projected at the highest growth rate due to the ease of management and specialized services that are offered by service providing companies. By Application: Blood & blood products, Stem cell products, Tissue & tissue products, Cellular & gene therapy products, and Vaccines and therapeutics. Vaccines & Therapeutics is anticipated to grow at the fastest rate owing to biologics production growth and increasing government funding for the promotion of usage of biologics to treat diseases. By End-user: Pharmaceutical and biotechnology companies, academic research institutes, contract research organizations, and other end users. Other end user segment primarily includes cell banks, small cell culture laboratories and consultants, microbiology laboratories, immunology laboratories, molecular laboratories, animal facilities, toxicology laboratories, and media/sera manufacturers. Pharmaceutical and biopharmaceutical companies are expected to account for the largest share due to an increased usage of these products for the drug development process and drug manufacturing process. CROs provide customized services and efficient management of the entire viral inactivation process. Hence, these are expected to gain considerable share during the forecast period. By Geography: North America, Europe, Asia and Rest of the World (RoW). North America has dominated the market during the forecast period due to the adoption of many methods by blood testing center. The splendid biopharmaceutical industry in the US and Canada is expected to fortify the market for viral inactivation in North America. Some of the dominant players in the viral inactivation market are Sartorius AG, Merck KGaA, Parker Hannifin, Rad Source Technologies, Clean Cells, WuXi PharmaTech (Cayman) Inc., and Danaher. The other market players include Charles River Laboratories International, SGS S.A., Texcell, Inc., Viral Inactivated Plasma Systems SA, Macopharma, TERUMO BCT, INC., Weigao group, V.I.P.S. SA, Cerus Corporation, BioReliance, Thermo Fisher Scientific Inc., and others. The report covers in-depth analysis of Global Viral Inactivation Market. The report assesses the market products pipeline by stage of development (early development, pre-clinical, clinical and in approval), by application (Trauma, Hemorrhage, Coagulopathy, Influenza, Heart Valve diseases, and others). In addition, the report includes key insights on other development activities, including (but not limited to) – licensing (In and Out), collaborations, acquisitions, reimbursement, patent, and regulatory designations. The report includes in-depth company profiles of key players in the Global Viral Inactivation Market. The company profile includes key information on the overview, financial highlights, product portfolio, business strategies, and key recent developments. The report highlights information on emerging companies with potentially disruptive technologies and new market entrants. Data Collation (Primary & Secondary) In-house Estimation (Based on proprietary databases and Models) Market-related information is assembled from both primary and secondary sources. Primary sources involved participants from all global stakeholders such as experts from several related industries and suppliers that have been interviewed to obtain and verify critical information as well as to assess prospects of the market. The participants included are CXOs, VPs, and managers. Plus, our in-house industry experts having decades of industry experience contribute their consulting and advisory services. Secondary sources include public sources such as regulatory frameworks, government IT spending, government demographic indicators, industry association statistics, and company publications annual reports press releases along with paid sources such as Factiva, OneSource, Bloomberg among others. Top-down and bottom-up approaches: The overall market size was used in the top-down approach to estimate the sizes of other individual submarkets (mentioned in the market segmentation by product, type of manufacturing, and disease) through percentage splits from secondary and primary research. The bottom-up approach was also implemented (wherever applicable) for data extracted from secondary research to validate the market segment revenues obtained.

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int neighbourcount(<geometry>geometry, int point_num) When running in the context of a node (such as a wrangle SOP), this argument can be an integer representing the input number (starting at 0) to read the geometry from. Alternatively, the argument can be a string specifying a geometry file (for example, a .bgeo) to read from. When running inside Houdini, this can be an The number of the point whose neighbours you want to count. The number of points that are connected to the specified point. A point is connected if it is adjacent in some polygon, is one of the four surrounding points in a grid or NURBs surface, or in some other manner directly shares an edge with point_num. Returns 0 if there is no input, or if the point number is out of range.

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This course brings together the four necessary communicating skills required to get to know the language: oral comprehension, written comprehension, oral expression and written expression. It is held 2 h/week, when it comes to academic courses, or more than 2 hours/week, for intensive courses, depending on each case. Pre-teaching:in order to introduce the student to the subject. Teaching: of new structures and vocabulary using a written or oral text. Guided Practice: making easy exercises related to the topic. Independent Practice: where the student uses all learnt in other similar topics. Evaluation: where the teacher checks what the student has learnt and the results achieved with this method. TKT preparation course What is the Cambridge Teaching knowledge Test (TKT)? The Cambridge TKT focuses on the teaching knowledge needed by teachers of primary, secondary or adult learners of English, anywhere in the world. It will increase your confidence and enhance your job prospects. What is CLIL? CLIL stands for Content and Language Integrated Learning. It refers to teaching subjects such as science, history and geography to students through a foreign language. This can be by the English teacher using cross-curricular content or the subject teacher using English as the language of instruction. Both methods result in the simultaneous learning of content and English. How can TKT help my career? Preparing for TKT will help you grow in confidence as a teacher and give you the knowledge and skills that will help you develop your career. You can take TKT whatever your background and teaching experience. The qualification is designed to be accessible, with no formal English language requirements for candidates. Why should you prepare with us? Our team is formed by experienced professionals who use official Cambridge material, for a more complete and efficient formation.Furthermore, we offer the opportunity to sign up for any of the official Cambridge exams. What’s in the exam The TKT is divided into separate modules. You can take them all, or just choose the ones that meet your needs. You have total flexibility in how and when you take the modules – you’ll receive a certificate for each one completed. To take the exams, you are advised to have a B1 level of English in the Common European Framework of Reference. The student’s development of the necessary skills required to succeed in the commercial and business world is the aim of this course. Obviously, English will be the communication language. Our Business English Courses are well-known by their strong technical character. Therefore, the student, apart from studying the used vocabulary in the business field, will learn current techniques used in the business world. The student will speak 70% about the most current topics, while the teacher will only speak to make an Error Analysis of the student’s mistakes. Finally, an evaluation/revision of everything learnt will take place at the end of each class.. This course has been designed in order to prepare the student for a special and particular event to take place in a short-medium term, such as: - Job Interviews - Business Trips - Public Speaking - Business Meetings - Preparation for level tests for academic years abroad

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The 2016 boating season is well underway. Every day, thousands of boaters head to the lake to fish, enjoy water sports, and relish in one of the greatest activities there is…boating. But, before you boat, you need to fuel up. Here are a few myths, facts, and solutions related to Ethanol Fuel in Boats. Fueling up a boat before hitting the water happens at retail gas stations for 95% of boaters according to a recent release from BoatUS. Due to recent changes by the federal government's Renewable Fuel Standard (RFS), risk of misfueling marine engines is on the rise. Here’s one reason why. The federal ethanol mandates require increasing amounts of biofuels—including corn ethanol—to be blended into the US fuel supply every year, such as E15 fuel. The approval of E15 fuel is putting boaters who fuel up at retail locations at risk because biofuels ARE NOT recommended for use in boats of any kind. One mistake at the gas pump can be a source of expensive, warranty voiding repairs and dangerous engine failure. Here are a few things to keep in mind the next time you hit the pumps. 1. E0 vs E10 vs E15 and how it affects your marine engine. Three of the most common types of gasoline currently found on the market are E0, E10, and E15. The “E” stands for Ethanol and the number represents the percentage of ethanol in unleaded gas. E0 is 0% Ethanol and 100% unleaded gasoline E10 is 10% Ethanol and 90% unleaded gasoline E15 is 15% Ethanol and 85% unleaded gasoline For marine engines, gas with 10% ethanol or less is recommended. Ethanol fuel in boat motors can put a quick damper on your weekend plans. One of the unfortunate characteristics of ethanol is that it attracts and absorbs water. Gasoline with ethanol can absorb roughly 10 times as much water and still burn through the engine. However, when water comes in contact with ethanol blended fuel, the fuel and water can separate to form distinct layers in your tank. The upper “gasoline” layer will be depleted of ethanol and have a reduced octane level. The lower “phase separation” layer will be a corrosive mix of water and ethanol and no chemical agent or fuel additive can be added to E10 gasoline, in a reasonable quantity, that will fully prevent phase separation or recombine a phase-separated layer. An engine won't run on the water-soaked, highly corrosive ethanol solution that sinks to the bottom of the tank. 2. Ethanol in Missouri fuel On January 1, 2008, the Missouri Renewable Fuel Standard became effective. Under this standard, all gasoline offered for sale in Missouri must contain 10% ethanol. A few exemptions to the standard allow gasoline without ethanol to be sold: - - When ethanol blends purchased at wholesale exceed the price of gasoline - - When selling premium unleaded gasoline with an octane rating of 91 or higher - - Gasoline sold at airports - - Gasoline sold at marinas 3. What to look for at the pumps. Marine refueling stations are your best options for ensuring you’re getting the proper fuel for your boat and reducing the risk of damages caused from ethanol fuel in your boat engine. If you choose to refuel on the way to the lake, be sure to check the pump first. In the state of Missouri, there is not a requirement for ethanol labeling on gasoline dispensers. Some gas pumps may offer both E10 and E15 or have a blender pump that is used for Flex-Fuel vehicles. Even though E15 can be less expensive than E10 fuel, the higher the risk of engine and fuel system damage is probably not worth the savings. 4. Transitioning from E0 to E10. Ethanol free fuel is the best option for marine engines, but E10 can still be used if necessary. The most likely time for fuel problems to occur is when you first begin using ethanol-blended fuel, because of phase separation. If your boat is currently fueled with Ethanol-free gasoline and you choose to transition to E10, there are few things to keep in mind. - - Check for water in the fuel tank. If you discover water in your fuel tank, pump the tank until it is dry. When you remove the fuel, place it in a clear container for inspection. If the fuel is not clear or has a bad or sour odor, you need to clean the tank. - - Add a quality cleaner that will help clean deposits in the engine. - - Fill the entire tank with E10 fuel. - - Monitor the filters and check for clogging. 5. Ethanol Myths Myth: Additives can prevent any issues caused by ethanol-blended fuel Fact: The only solution for preventing phase separation is keeping water from accumulating in your tank and using quality, ethanol-free fuel. Myth: Fuel that has been separated can be used again if a fuel additive is used. Fact: Once a fuel has gone “bad” it is no longer useable. The only option is to remove the fuel. However, high-quality fuel additives do aide in preventing sediment, gum and varnish buildup that forms when fuel goes bad. 6. Fueling up in 2017 The Environmental Protection Agency (EPA) is currently asking for comments on a proposal to increase the amount of ethanol that must be blended into the nation's gasoline supply for 2017. If adopted, these proposed levels will require the use of a record amount of ethanol, forcing higher-level ethanol fuel blends (E15) into gas pumps and at more gas stations. The Boat Owners Association of the United States (BoatUS) is urging all recreational boaters to send a message today urging the EPA to lower the ethanol mandates to ensure an adequate supply of fuel that will work with recreational boat engine and fuel systems and offers a simple way to send comments by going to: http://goo.gl/yczkuK. The deadline for public comments is July 11. Take a minute and leave a comment to help protect the future of fuel for marine engines. Fueling is an important part of any trip to the lake. Don’t let misfueling bring your weekend plans to a halt. Check your tanks, check the pumps, and enjoy the lake! If you have any questions or would like to know more about our boats, products and services, give us a call at 660-747-0388.

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CALENDULA: health and beauty in a flower 19/12/2015 - Calendula is a flower with a thousand virtues that can not miss in creams ... Calendula: health and beauty in a flower Also known as the "Marigold", calendula is a herbaceous plant flowers yellow-orange color, that grows almost anywhere in temperate climates: in the gardens, along the roads, in fallow fields, vineyards. The most important active ingredient content in the flowers of calendula is a saponin, responsible for their anti-inflammatory and healing. Among other active ingredients contained in the flowers, remember also carotenoids, polysaccharides, volatile oils and essential fatty acids, which make this plant one of the herbal medicines with the largest range of therapeutic and cosmetic applications. Used as a tea or herbal tea, dried calendula petals are useful in combating and preventing atherosclerosis, problems of circulation and varicose veins, as well as regulate the menstrual flow. In the form of ointment, marigold promotes wound healing and is useful in the treatment of insect bites, mycosis (especially nails), and any other condition to irritation or inflammation of the skin. But perhaps the most famous preparations made from calendula are creams, activities nourishing, moisturizing, soothing and restorative. Its effectiveness, combined with its sweetness, make it ideal for sensitive skin of infants and children, so that the creams made from calendula are often used for the treatment and prevention of sunburn, even diaper. A flower, then, a thousand virtues, which should never miss armory health and beauty of each of us. Chiara De Carli

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For they could not love you but still your love was true,This world was never meant for one as beautiful as you. And when no hope was left in sight on that starry starry night, You took your life as lovers often do; But I could have told you, Vincent, —Don McLean, "Vincent" Vincent Willem van Gogh was a famous post-impressionist artist, famous for his hard life, insanity and vividly colored paintings. His last name is pronounced the Dutch way: "van" rhymes with "one", and "Gogh" is a soft Southern Dutch guttural G, a short O (as in "log"), and another soft guttural G. As with any Dutch last name, the "van" is spelled without its capital letter when preceded by the first name or initial. Van Gogh was born to a minister and his wife, a Replacement Goldfish to their dead son. After growing up with his brother Theo and going to boarding school, he left his small home in the Netherlands to work at an art dealer. After expressing rage at the thought of art becoming a commodity, he was fired. He fell in love with the landlord's daughter Eugénie Loyer, who rejected him when he finally confessed his feelings. This would start a chain of romantic failures. Van Gogh proposed to his cousin Kee Vos-Stricker, who had no interest in him. Van Gogh held his hand over an open flame, saying he would hold it there until he could change her mind. She absolutely refused him. Van Gogh fell in love with a prostitute named Sien Hoornick. Van Gogh's father did not approve of the marriage. She drowned herself in the river in 1904. Van Gogh fell into depression, but decided to enroll in a school to do something with his life. He befriended Henri de Toulouse-Lautrec there, but because of his problems their friendship fell out. He then moved to Arles, which he described as a disgusting and filthy city. This didn't show in his artwork, as he made some of his most colorful and vibrant pictures of the city there. He found a friend in Paul Gauguin, and waited for him to join him at the yellow house he bought in the country side. He painted paintings for Gauguin and asked after him constantly, which annoyed Gauguin. In a fit of his mental illness he cut off the lobe of his ear in a fight with Gauguin, begging him not to leave. He gave the bit of flesh to a prostitute at a hotel. After increasing tension and a state of angry paranoia and mental illness, he returned home. There 30 townspeople made a petition to get rid of him. He was having paranoid delusions of people trying to poison him. They called him fou roux (the redheaded fool/madman) and had him committed to an asylum. He threw himself into painting at the asylum, making brilliant painting after painting. After he left, he remained reclusive in his yellow house. In 1890 he shot himself in the chest with a revolver in the middle of a field. Unfortunately for him, he survived and had to stay in the hospital another two days, eventually dying of infections from the gunshot wounds. Recent academic research and told on a recent segment of 60 Minutes that van Gogh might not have shot himself as the tale goes but received his fatal wound as a result of a village boy shooting him by accident. Tropes applying to the artist: - The Alcoholic - Beard of Sorrow - Common Knowledge: Vincent didn't cut off his whole ear. It was only his lobe! - Dead Artists Are Better - Dogged Nice Guy - Driven to Suicide: Sort of. He did shoot himself, but it took complications from the injury to finish the job. - Forgets to Eat: Another thing that contributed to his poor health. He often used the very little money he got from his brother to buy art supplies, and the only thing he'd buy to consume was coffee and thujone. - Genre Popularizer: Post-Impressionism - Ho Yay: Vincent van Gogh and Paul Gauguin, at least from Vincent's side. He kept begging Gauguin to come and live with him in Arles and gave him dozens of paintings, basically saying "please be my friend." Unfortunately for him, Gauguin didn't really respect him as an artist and was probably a little creeped out. Their relationship began to deteriorate and poor Vincent cut off his ear with a razor to keep Gauguin from leaving him. Gauguin's response to this was to... leave, and Vincent was soon after committed to a mental hospital. He often asked his brother Theo to have Gauguin come and see him, and at one point he wrote "I think about him all the time." - It Is Pronounced "Tro-PAY": The correct Dutch pronunciation of Van Gogh is as follows: "van" rhymes with "one", and "Gogh" is a soft Southern Dutch guttural G, a short O (as in "log"), and another soft guttural G. Not "Van Goth", "Van Goff" or "Van Go". Note that Van Gogh was born in the southern province of Brabant, so he wouldn't have used the rough guttural G that's used in standard Dutch. - Loners Are Freaks - Lost in the Maize: He attempted suicide in a cornfield, and supposedly his last painting was of one. - Mad Artist: Famously. The Long List of his many health problems: - Bipolar disorder - Temporal Lobe Epilepsy: Random seizures without altered conciousness, but ending in a state of confusion and paranoia. - Thujone poisoning (from his absinthe alcoholism) - Lead and chromium poisoning (chromium yellows had recently been introduced and he used a LOT of them). - Hypergraphia (a condition in which you feel the need to write continuously, which might explain why he wrote 800 letters in his lifetime) - Sunstroke: He often got so wrapped up in painting outside he forgot that he was about to pass out. - Some historians believe he was also a paranoid schizophrenic. - Magnum Opus: The Starry Night is considered his best. - Mood Swinger: Justified, as he was bipolar. - Must Have Caffeine: Letters to his brother indicate that he ate close to nothing and stayed alive on coffee and absinthe. - Never Accepted in His Hometown: As mentioned above, 30 townspeople made a petition to get rid of him. - Nice Hat - Not Good with People - Picture Pastiche: Just one example: Look familiar? - Post Something Ism: Post-Impressionism, which became popular when his work gained acceptance. - Reclusive Artist - Redheaded Hero - Replacement Goldfish: Vincent had an older brother who died at birth, also named Vincent, born on the same day as him, but one year earlier. Every week when his family went to church, Vincent would have to walk past a gravestone with, essentially, his name and birthdate on it, only off by one year. - Starving Artist: Literally. Poor nutrition also was a contributing factor to his terrible health. - There Are No Therapists: At least until Saint Remy. Historians have speculated that a lot of his problems came from him actually being a paranoid schizophrenic, which couldn't have been treated then. - The Unpronounceable: His surname; in English people argue whether it's Van Go or Van Goff, while the actual Dutch pronunciation is quite different from either. - Vindicated by History: Van Gogh's art was never highly regarded until after his death, when a series of memorial exhibitions cemented his reputation. He is now generally considered one of the greatest artists who has ever lived.

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Can We Conquer Drug Resistance in Lung Cancer? At the beginning of the last century lung cancer was a rare disease. However, as early as the end of the 1900s, it had already become the leading cause of preventable death worldwide. In 2016, the disease is expected to cause approximately 158,000 deaths in the United States alone, more than colorectal, breast, and prostate cancers combined. Therefore, finding a better cure for this deadly disease is a pressing need. Lung cancer has poor prognosis, as it often stays asymptomatic until it is well advanced. Tobacco smoking is responsible for approximately 90% of lung cancer cases, contributing to lung cancer surpassing heart disease as the leading cause of smoking-related mortality. Exposure to other types of carcinogens, such as asbestos, radon, or to a particularly polluted atmosphere, have all been implicated in disease development among non-smokers. 85% of all lung cancer cases are of the non-small cell subtype (NSCLC). Advanced molecular techniques have identified genetic susceptibility in NSCLC linked to amplification of oncogenes and inactivation of tumor suppressor genes. The most important genetic abnormalities detected are mutations involving the ras family of oncogenes. The Genetic Basis of Drug Resistance More than a third of NSCLC cases among the Asian population, where tobacco smoking is on the rise, present mutation in the epidermal growth factor receptor (EGFR) gene, which has become a popular target for the development of new anticancer agents. These mutations (deletions in exon 19, and exon 21 L858R mutation) generally arise within the tyrosine kinase domain of the receptor contributing to the expression of a constitutively active form of the protein, which leads to aberrant cell multiplication. The first generation of inhibitors against the EGFR kinase activity (EGFR-TKIs), such as gefitinib and erlotinib, have been effectively utilized as first-line treatment of advanced NSCLC harboring activating EGFR mutations. However, in these patients drug resistance eventually arise, in most cases as a result of secondary mutations emerging in EGFR (EGFR T790 M, also known as “gatekeeper” mutation). Second and third generation EGFR-TKIs, such as afatinib or osimertinib, were designed to overcome resistance and more potently inhibit EGFR activity. Third generation TKIs are also capable of crossing the blood-brain barrier, and are therefore more likely to have activity in brain metastases, which sometimes develop within a year of treatment. Given the difficult clinical path of lung cancer treatment which takes patients through disheartening relapse before the more advanced EGFR inhibitors can be prescribed, it has recently been suggested that the third generation EGFR-TKIs should become first-line treatment for EGFR mutated NSCLC. A New Hope for Treatment Resistant Patients? It is worth noting that for a subpopulation of NSCLC patients carrying non-canonical mutations in EGFR (exon 20 insertions), there is still no convincing therapy approach since they seem to be refractory to EGFR-TKIs. For these patients combination strategies that hit multiple pathways at the same time have been proposed and novel TKIs are currently being investigated. To address the need of finding new treatments for this subpopulation of patients, researchers at CrownBio have developed a unique set of patient-derived models (patient-derived xenograft, PDX) that specifically carry non canonical EGFR mutations and that have been trialed with a range of EGFR inhibitors – including first, second, and third generation TKIs as well as Erbitux® (cetuximab), an anti-EGFR antibody that binds to the receptor to inhibits its activity. Similarly to patients in the clinic these newly developed models showed poor response to standard of care TKIs. More importantly this study was the first one to report a poor outcome following cetuximab treatment in this class of NSCLC, suggesting that CrownBio’s newly developed models represents invaluable assets to predict a patient’s response and for preclinical investigation of drug efficacy before new agents enter the clinic. CrownBio’s NSCLC models have already been successfully utilized in preclinical research to validate the antitumor efficacy of novel compounds or novel combination strategies. For more information on CrownBio’s comprehensive collection of NSCLC PDX models visit HuBase™, our curated, online, searchable database of phenotypic and genotypic data, patient information, growth curves, and standard of care treatment for our HuPrime® PDX models. Alternatively email us today for a copy of our Models of Resistance Application Note.

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Click a title to view the article.> The following is an explanation of how scientists working on the Dog Genome Initiative set out to identify genes that determine behavior or inherited diseases in dogs. Research methods have evolved to include other approaches in the 15 or so years since then, but this remains a good explanation of genes and gene mapping. It was written for non-scientists by Dr. Polly Matzinger, an immunologist and sheepdog handler. Start by thinking of GENES as pearls on a string (made of DNA instead of oyster saliva). Dogs, like people, have lots of these strings, a bit like a multi-strand pearl necklace. The strings are called chromosomes. Now suppose that you wanted to know how many of these genes it takes to control something as complicated as the behavioural trait we call “eye” and you wanted to know which particular ones, on which particular strings, do the job. If you look at the chromosome strings in a microscope, they all look pretty much the same, though some are longer than others. Suppose that the third gene on the first chromosome string has something to do with the INTENSITY with which an animal pays attention to an object, the 11th gene on the second chromosome controls whether it pays attention by LOOKING rather than listening or smelling, the 7th gene on the third chromosome controls HOW LONG it will continue to pay attention, and the 22nd gene on the 4th chromosome controls whether it pays attention to STATIONARY or only moving objects.> How would you ever be able to find this out? remember, the chromosomes all look the same. This is NOT an easy task and for years we didn’t have the technology to do it, but recently several interesting and odd quirks of nature have been discovered that open the way. One of the odd quirks is a type of DNA called ‘micro-satellite’. These are funny little areas where the DNA string can stretch and contract. They are a little like the leaves of a dining table that can be used to make it longer. The micro-satellite extensions are always made of the same stuff but sometimes they are very long (a boardroom table, lots of extensions added) and sometimes short (a card table). There are about 4,000 of these in most species that have been studied and they are scattered all around the genome (another word for the total number of strings that make up the pearl necklace). So our picture of the DNA pearl necklace begins to get a bit more detailed: No one really knows why the micro-satellites exist, but the current view is that they are due to slippage mistakes made during the repair of the strings, which, being very delicate, periodically break and need repair. The micro-satellites have three properties that make them incredibly useful to researchers who want to find the genes that control particular traits. First, because the micro-satellites are always made of the same stuff, they can be located and mapped. For example, chromosome number one in dogs (the chromosomes were originally numbered in order of length, since there was no other useful way to tell them apart: number one is the longest) might contain a micro-satellite 1,000 units in from the left end, and another one that is 450,000 units further down to the right and so on. People have been working on the micro-satellite maps of the chromosomes of different species for a couple of decades and some of the maps are getting very close to complete. Second, their lengths will vary randomly, so the one that is 1000 units in from the left end might be 92 units long, whereas the next one down might only be 31 units long and so on. Each micro-satellite therefore has two properties that identify it; its position and its length (like mapping the co-ordinates of a city and also knowing its size) Third, the more distantly related two individuals are, the more different their micro-satellites will be. Breaks in dog strings, for example, will be randomly repaired differently from those in human strings, not because there’s anything inherently different about dog DNA but simply because the breaks are random. So, although both humans and dogs carry genes for blue and brown eyes, and red and black hair (and probably for behavioral things like attention spans and ability to see and hear), the years of breaks and repairs that have gone on between us will lead to differences in the positions and lengths of the micro-satellites Border collies and newfoundlands, though not as different as humans and dogs, have been separated for long enough that many of their micro-satellites are different. So people like the Dog Genome researchers can look at the micro-satellite map of, say, chromosome two and know whether the chromosome came from a border collie, or a newf, just by looking at the micro-satellites. I’m making a couple of assumptions here. In the position where the border collie has the gene for paying attention by looking (Lo), I’m assuming that the newf has a gene for paying attention by listening (li). This may not be true, of course, but let’s use it for illustration. The same sort of thing holds for chromosome four, where sits the gene for paying attention to stationary things or to moving things. Lets say that the border collie has a gene that induces it to pay attention to things regardless of whether they are moving or stationary (a scared sheep? The sheep that’s been backed into a corner?), while the newf mostly pays attention to things that are moving (drowning people rather than the rocks their boat crashed on). So at position 22, the border collie chromosome has the stationary/moving gene (Sm) and the newf has the moving gene (m). The two chromosomes will also have different micro-satellites. Now remember that nobody knows where the behavior genes are (or even how many exist, or which types of behavior are influenced by genes). They only know the positions and lengths of the micro-satellites. How can they use this information to find the behavior genes? They start by mating a newfoundland to a border collie. Now, in every individual, each one of the chromosome strings is actually paired up. There are two copies of each chromosome, one received from the mother and one from the father. So the border collie and the newf each has a pair of chromosome 2s and a pair of chromosome 4s. In the process of making eggs and sperm, they split these pairs up and donate one half (a complete set of singles) to all their progeny. All the puppies will thus have one set of chromosome strings from their mother (the newf, in this case) and one from their father. So their sets of chromosomes 2 and 4 will look like this. By analyzing the behavior of this first cross, the scientists can make some guesses about the relative strengths of the different behavior genes, (though they won’t yet be able to say how many there are or where they sit on the chromosomes). For example, if the puppies tend to look rather than listen, then looking (Lo) would be said to be DOMINANT over listening (li). If they tend to do both, paying attention with both their ears and their eyes, the genes would be said to be CO-DOMINANT. For the sake of this example, let’s say that they are co-dominant. Lets also say that the Moving vs. Stationary genes on chromosome 4 are not co-dominant, but that paying attention only to moving things is dominant over paying attention to both moving and stationary things. So the puppies of a newf by border collie cross would pay attention only to moving things and they would do it by both listening and looking. Good. This means that the first generation has taught us something, but not a whole lot. To learn more, we need to do some more breeding. We do this by breeding the puppies to each other (brothers to sisters) to make the second generation (called the F2 generation). Each parent will split its pairs of chromosmes, sending one copy (either the border collie copy or the newf copy) into the sperm or egg. The splits happen randomly so that a border collie type of chromosome 2 might end up going into the same egg as a newfoundland type of 4 etc. The puppies will therefore get all sorts of combinations of pairs of chromosomes. (Just like the progeny of a tri-color, prick eared bitch and a black, drop eared dog will come out in all the combinations of tri-color-drop eared, black-prick eared etc). Now things begin to get really interesting. We wait for the new puppies to grow up and then test them for the looking vs listening type of attention as well as for moving vs stationary attention. (The tests haven’t really been worked out yet. In fact, I think this is the most problematic part of the whole project, but that’s another story. Let’s pretend that good tests have been devised and let’s get back to the genetics, because the genetics will work for any trait, including many of the diseases for which good tests already exist). Suppose that we find an F2 puppy that Looks (and doesn’t listen) at both stationary and moving things. This is a dog that has copies of the border collie genes for LOOKING and STATIONARY/MOVING and doesn’t have copies of the newfoundland genes. We don’t know where these genes are yet, all we know is that we have found a dog that has them. So we take a little bit of blood, isolate the DNA from the white blood cells and look at the micro-satellite map. We find that both copies of chromosome 4 have a border collie type of micro-satellite pattern. We also find that both chromosome 2s are border collie type. But we can’t yet conclude that the Looking and Stationary/Moving genes are on chromosomes 2 and 4 because this dog also has two sets of border collie chromosomes 7, 9 and 13. Though these chromosomes don’t carry any genes that we’re interested in, we don’t know that yet. All we know is that chromosome sets 2,4,7,9 and 13 are pure border collie. Let’s say that sets 5,6 11 and 14 are pure newfoundland and all the rest are mixed pairs, where one comes from the border collie and the other from the newf. We can therefore guess that the LOOKING gene (Lo) and the gene for STATIONARY/MOVING attention (Sm) are somewhere on chromosomes 2,4,7 9 or 13. To pin point it a bit closer, we need to find other dogs that have the border collie trait. Suppose that we now find one that looks (and doesn’t listen) but only to moving things. We know therefore that it has the border collie Looking gene (Lo) and the newfoundland moving gene (m). When we analyse the DNA from its white blood cells, we find that chromosomes 1,2 and 7 are pure border collie, 4, 8, 9 and 15 are pure newf and the rest are mixes. We’re now down to two choices for the Looking gene!! It must be either on chromosome 2 or 7 because these are the only two that are pure border collie in BOTH dogs. We haven’t learned anything more about the Stationary/moving gene because this dog has the dominant trait (looking at only moving things) that can result from having either two pure copies of newf genes (m) or one copy each of the border collie (Sm) and the newfoundland (m) gene. So we look at more dogs, hoping to find some more that have the Looking trait. We test them, find the ones that have the Looking trait rather than the Listening trait, bleed them, look at their DNA and . . . eventually . . . after a LOT of work, we pinpoint the Looking (and the Listening) genes to chromosome 2. We’ve now accomplished the first step. We have mapped a behavior gene. We have learned a LOT from this. First, that there really is a gene involved in controlling this behavior, in the same way that there are genes governing ear prick and coat color. We’ve learned that a single gene is at work (not always true) and that it is co-dominant with its partner, the Listening gene. This means that, if we want dogs that will both look and listen, we’ll need to keep making hybrids (like tomatoes) because this is a trait that needs both genes and therefore will never breed ‘true’. Every time we breed two looking/listening dogs together, we will get some puppies that look (about one fourth of them), some that listen (another fourth) and about half that do both. Now, please remember that this is a concocted fantasy example. I don’t think that anything is known yet about the number, position, dominance, co-dominance or recessiveness of genes for behavior. I have just given an account of how the search is being done. I think we can pretty well say that genes for behavior do exist. Anyone who has worked with different breeds of dogs can’t help but know this. And hopefully, if these amazingly dedicated people get enough funding to do the work, we’ll know the answers to some of our questions some day. The following article was published by the United States Border Collie Club in 1995, just after the Border Collie was recognized by the AKC. At that time, the AKC stated that it would close its studbook to non-AKC Border Collies three years after it began registering the breed. In the end, it never did close the studbook to Border Collies registered with the working registries. However, this article is a good explanation of the effect that setting a conformation standard and breeding to it has on the working ability of the breed. 1. Basic Genetics We all learned basic genetics in high school biology, but most of us who don’t use it every day have forgotten the details, and those who remember it don’t necessarily see the connection between Mendel’s work and the practical questions of dog breeding. In order to understand the genetic basis of the USBCC’s objection to AKC registration of the Border Collie, we may have to start back at the high school biology level and work forward. In the first place, heredity, the information passed from one generation to another, is contained in discrete particles which Mendel called “genes.” These genes are carried, somewhat like beads on a string, along microscopic bodies called “chromosomes.” Genes are arranged in constant linear order along a chromosome; each has a specific “address” (called a locus) on a specific chromosome. Chromosomes occur in pairs, one from mother, one from father. Each member of the pair has, at the same address, the same gene, but possibly a different form of the gene (called an allele). There are probably close to twenty thousand genes altogether in the dog. The only ones that are important to us are the ones that have identifiable alternative alleles. In other words, the only reason we are aware of the E gene which causes black hair is by the existence of its allele, e, which, if present on both chromosomes, causes red hair. The vast majority of the genes that make up the whole dog are not even identified; at most, we deal with a few dozen. 2. Recombination and Linkage Behavior traits which make up the Border Collie: E. Speed and agility F. Interest in moving targets All come from different sources: A. setter/pointer; B. spaniel; C and D. unknown (maybe some older breed of sheepdog; E and F. greyhound/whippet. How did they all come to be assembled in the modern sheepdog? During the production of eggs and sperm, the chromosomes are scrambled, and one of each pair is passed to each germ cell. There is no preference for those originating from, say, the mother, to be passed together as a group. Furthermore, actual genetic material of those chromosomes is regularly exchanged between members of the pair during the process, so that in the end there is no such thing as “mother’s chromosome.” All of the chromosomes carry genes that originated with both mother and father. This is the very important process called recombination. The closer two genes occur along the linear order of the chromosome, the more likely they are to remain together in the next generation. In fact, we can actually “map” chromosomes in organisms where we can do large numbers of breeding tests, (fruit flies, mice, etc.) simply by measuring how often particular alleles of two genes remain together from one generation to the next. In extreme cases, where this “linkage” is as close as one molecule to the next, they may only separate in one case in millions. It is very rare, however, for two recognized, identifiable genes’ addresses to be so close together. What are the implications of recombination and linkage? First, it would have been impossible to assemble into one breed all the different genetic traits that go into Border Collie instinct if they were very tightly linked together. Suppose, for instance, that the spaniel has the traits “crouch; no eye” and the setter has “no crouch; eye.” If the “crouch” gene were tightly physically connected to the “eye” gene, the two original combinations of alleles would still be together. We would have dogs which crouch, but have no eye, and dogs which have plenty of eye, but do not crouch. If we couldn’t recombine those alleles, we could never arrive at the “crouch; eye” combination we treasure in our working dogs. The original litters in which spaniels and setters were crossed with old-fashioned sheepdogs, and the next few generations as well, must have included the whole spectrum: crouch, eye; crouch, no eye; no crouch, eye; and no crouch, no eye. From those, the ancestors of the Border Collie were selected: those which had eye and crouch together. The more completely random the recombination among these genes, the easier it would have been to get these new combinations. The flip side of this, though, is that now that we have assembled within our breed the combinations that we want, it is just as easy for them to come apart in future generations if no effort is made to hold them together by selective breeding. 3. Fixing a Combination Genetic combinations are said to be “fixed” within a breed if every member of the breed has exactly the same combination of alleles at a particular locus. In the Belgian Sheepdog, for example, the black color gene has been “fixed”; no other alleles of the E gene are present within the breed. A single gene of this sort is easy to fix. We simply remove from breeding all individuals who either are the wrong color or ever produce puppies who are the wrong color. It is also possible to make progress toward fixing the normal allele of a gene which causes a genetic disease by such selective methods. Generally speaking, the Border Collie does not have any fixed genetic combinations. In appearance, this is obvious. Even in herding, however, there is a spectrum in almost every one of the traits we value. A dog may have very little eye, or so much that he freezes (like the pointer who is “staunch on point”) and cannot be brought to move the stock; he may have no balance at all, or such a strong sense of it that he cannot be persuaded to move off the balance point; he may lack power and be unable to move even the lightest stock, or he may have so much that sheep flee from him the moment he comes onto the field. In all of these, the combination that produces the middle ground is the most desired; it is also the most difficult to fix genetically. After all these generations, a litter of the best-bred working Border Collies still may have perfect working dogs, mediocre dogs, and useless dogs. Alleles are not always dominant or recessive; often the combination in which the two alleles are different (heterozygous) is intermediate between the two homozygous combinations. Some of our most desired genetic combinations in herding behavior may well be heterozygous pairs: they can never be fixed in a population because they will always produce some of each type of homozygous pair. Because these complex traits cannot be fixed in the breed at their optimum levels, because the alleles and combinations of alleles that produce mediocre and useless dogs still occur in the breed, the risk of losing the best combinations is always at hand. If every Border Collie carried the precise combination that produced a perfect worker–for light sheep or cattle, for trial or farm, for Arizona or Scotland, for the tough handler and the soft–we would have nothing to worry about. No matter which of our dogs were chosen to be bred for “conformation” showing, all of them would still be working Border Collies. 4. Complex Genetic Traits The red Border Collie, like the chestnut horse, is the result of a recessive gene pair. In the case of the dogs, the dominant (black) is called B, and the recessive (red) is called b. A black dog may be either BB or Bb; the red dog is always bb. Two black dogs may have red puppies if both of them are Bb; the b can come from each parent to produce bb in the pups. Statistically, one out of four pups with such a cross will be red. If either parent is BB, though, the combination can’t produce red pups. If both parents are red, bb, then all their puppies will be red; there is no B available from either parent to make a black pup. The end product of most genes is some sort of biochemical substance. In the red color, the chemical is a pigment called eumelanin. This is one of a group of pigments, the melanins, which cause color in animal skin, hair, and feathers. It is responsible for very dark brown or black color. All Border Collies have in their hair a red version of melanin, called phaeomelanin. In the black dogs, the black eumelanin covers the appearance of the red. If you’ve ever looked closely at your black dog in bright light after he has spent a lot of time in the sun, you will see a faint red glow to his hair. The eumelanin has been bleached by the sun, and the red color is showing through, however slightly. Only the dominant version of the color gene results in eumelanin production; if the dog has two copies of the recessive version, he will have no eumelanin. His hair will contain only the red pigment, and anywhere that he would otherwise have been black, he will instead be red. This means he may have the same variety of white markings as any black Border Collie; he may be tri-color, with lighter brown markings in all the usual places; he may even be a red merle instead of a blue merle. His nose and toe pads, which would be black on a black dog, are red-brown. But why are there suddenly more of them? One reason is that the red gene is present in some of our favorite breeding lines. The first recorded red Border Collie was a bitch named Wylie, grandmother of the famous Dickson’s Hemp (153). The recessive gene passed through the generations to J. M. Wilson’s Cap (3036) who appears in the pedigree of Wiston Cap at least 16 times! Wiston Cap carried the red gene and passed it to many of his sons and daughters. Our current Border Collies tend to have many crosses of Wiston Cap in their background; each one increases the chances of receiving that e gene. Crosses on both sides of the family, likewise, increase the chances of a double dose and the appearance of more and more red dogs. Unlike most simple genetic traits, however, good (or bad) hips don’t result from a single pair of genes. With a single pair, like the “red” genes, the probability of each genetic combination in the next generation is easy to measure. We know exactly how many red pups, statistically, to expect from any combination. With hip dysplasia, on the other hand, we have no idea what to expect in a litter of pups, even if we have x-rayed both parents. Instinct and behavior, like hips, are affected by a large number of genes; some may be recessive like the b; some may be dominant like the B. The problem is that we don’t know how to identify any of them, and we have no idea how many there are. If we had some kind of behavioral measurements on all the members of hundreds of litters and their parents and offspring, we could make a start. We aren’t even close. We have no real measurements at all; our assessment of herding ability is subjective, and deals with the whole dog and his ability to get the job done. Studies by Scott and Fuller on spaniels revealed the genes involved in the behavior known as “crouch”; the crouch itself is controlled by two major genes, with the crouch (or sit) dominant over the stand. The quiet attitude was also controlled by two genes, with the quiet behavior recessive to the more active. The whole pattern of quietly crouching, then, results from four genes altogether. The number of different genetic combinations that can be formed from 4 (2-allele) genes is 81! If the parents are heterozygous for all four of these genes, any of these genetic combinations is possible in the same litter. What does all this mean to the Border Collie? Imagine, if that simple quiet crouch behind the sheep depends on 4 separate genes, what must be involved in the entire collection of herding behavior: eye, balance, power, biddability, etc. And what must the chances be of accidentally combining the right factors to remake a herding dog, if those combinations are ever lost? The complexity of the genetics of behavior is probably not a surprise, but it is the basis of the entire argument that the performance dog must be bred for performance at every generation. The more genes are involved, the more different combinations are possible, the more easily they become separated and lost. If the dogs selected for breeding for conformation are not the ones with the best herding genes, the population will inevitably drift away from the wonderful performance combinations that have been selected in the breed for so many generations. Because the extremely complex instinct that makes up the working dog is not fixed in the population, constant selection is needed, at every generation, to maintain the best combinations. Any relaxation of this pressure will result in the increase in numbers of those dogs which have less than ideal genetic combinations. Breeding for any other purpose without also selecting for truly high quality working genes will inevitably result in the dilution of the working instinct within the breed. Genes may have more than two different alleles (there are 160 different alleles of the blood group gene, B, in cattle). The number of possible genetic combinations as we increase both the number of possible alleles and the number of genes rises abruptly. If we are dealing with, say 6 traits (see above), each with an average of only two gene loci involved, that is 12 genes; if they have only 2 or 3 possible alleles: If we are already trying to maintain some genetic equilibrium with all these possibilities, consider the additional burden of selecting at the same time for color, ear type, body size, coat quality, eye color, head shape, etc., to fit some arbitrary standard of appearance. The number of different genetic types becomes astronomical. The number of dogs that can fit all these separate standards for all these separate genes is, as Verne Grant stated it, probably less than one in the whole breed! The number that will come close is still very small. This is particularly true within a breed like the Border Collie where there is no genetic uniformity in appearance to begin with. When the number of available dogs for breeding becomes very small (as, for instance, those dogs who fit both a performance standard and an appearance standard), the result will be, unavoidably, an increase in inbreeding. Furthermore, the best, and indeed the only way to fix a set of alleles within a breed is through inbreeding. Members of the same family tend to carry the same genes, so breeding among them is the quickest way to “concentrate” those alleles we want. Concentration is a poor word, although it is the one usually used here; we can never have more than two copies of the same allele–a gene pair–so we cannot concentrate any further than that. What we can do is get more and more genes to be present in identical pairs, in other words, “fixed” within the breed. This condition of having identical alleles in a gene pair is called homozygosity. And it is exactly the increase in homozygosity that is the problem with inbreeding. In addition to producing a predictable appearance in your litters of puppies–if that is somehow a valuable thing–homozygosity does other things which are downright dangerous. Most (although not all) detrimental or even lethal genes are recessive (take CEA as an example), that is, they must be present in a homozygous pair to have their effect; increasing homozygosity leads to increasing the number of individuals with the damaging gene pair. For rather more complicated biochemical reasons, a general increase in homozygosity also leads to a decrease in general vigor and a greater sensitivity to stress–all in all, less healthy animals. Geneticists generally agree that genetic diversity within a population is always desirable. The more traits we try to fix in a breed, such as both performance and appearance, the less diversity we will have. There is a mathematical formula called the Hardy-Weinberg law which predicts that in a random-breeding situation the frequencies of different alleles will remain constant. The key is in the concept of “random” breeding; every male in the population has an equal chance of mating with every female and vice versa; every mating is equally productive. Variations in these constraints cause change in the frequencies of genes, and in the number of individuals with different genetic traits. One variation from randomness is viability. One is statistical sample size. With domestic animals, the most important is selective breeding. The fact is that among purebred dogs, there is no such thing as random breeding. It is the intention of breeders to change the frequencies of important alleles. In the performance of this function, breeders take advantage, quite correctly, of the ability of a single male to impregnate a large number of females. In animal breeding, a relatively small fraction of all the available males produces a very large fraction of all the offspring. The choice of those male dogs determines the future of the breed. We can all point to the presence in our pedigrees of such great stud dogs as Wiston Cap, Gilchrist’s Spot, Dryden Joe, Whitehope Nap, Welsh’s Don, etc. In the case of the Border Collie, these central dogs have all been great herding dogs in their own right, and great sires of herding dogs as well. The recent increase in the number of red dogs is a direct result of this system of breeding, arising from the popularity of Wiston Cap. This increase has been purely accidental, called “genetic drift,” and is typical of the change in genetic makeup in a population when mating is not random. The presence of large numbers of dogs with genetic defects–CEA, hip dysplasia, epilepsy, etc.–in any breed usually results from this sort of accidental selection. A popular stud dog carries genes, usually recessive ones which are not expressed in his own life, which are passed on in increased numbers to the next generations simply because he produces a disproportionate number of pups. Consider what will happen when the most popular stud dog is one who merely fits the appearance standard and so wins a show ring championship. He may or may not carry the particular, very complex combination of genes that makes a great herding dog. He may even be a good herding dog. If he contributes his genes to a disproportionate number of puppies, and if he is anything less than a great herding dog, his genetic contribution will lower the general level of herding ability within the breed. The extremely wide variety of appearances in the existing breed means that only a small number of our present herding dogs will be used in the breeding of showring competitors; at the very least, the genes in those great herding dogs who do not live up to the appearance standard will be sacrificed. 7. The Standard The existing Border Collie is not a breed without a standard. It has a very specific standard, by which dogs without registration papers and pedigrees can be Registered on Merit if they can demonstrate their herding ability to satisfy this standard. Whatever appearance standard is designed by the AKC and its chosen Breed Club (should it eventually designate one), it will not be the same standard to which the breed currently strives; it will therefore, by definition and unavoidably not be the same breed of dogs. Even though the initial registration will come from the existing breed, the next generation of “showdogs” will have been bred under a different set of selective rules, and will already be at least philosophically different. After three years, when the AKC closes its books and no longer allows dogs of the original breed to be used for breeding, the AKC breed will have become a separate entity, no matter what its name! This already happened at least once, when the “Lassie” collie was created. The working sheepdogs used to be called “collies.” They became “Border Collies” to distinguish them from the developing show breed. At the time of separation, there was no real distinction; anyone can tell the two breeds apart now. All of this is quite apart from the possibility of a standard being chosen which is simply inconsistent with the demands of the shepherding life. This may be in the written standard or in the fashions of judges who know nothing about these physical demands. This has already happened to some of the breeds (Labrador retrievers, for instance, are currently too heavy and short-legged to be of much use in the field; Siberian huskies tend to be showring winners with legs too short to run properly and with fluffy coats that cannot shed snow and ice; bearded collies look nothing like their ancestors, and have coats which obscure their vision, and collect burrs and mud). There has been some call for the USBCC to become the breed club so that we could set the standard and thereby avoid the problems of inappropriate physical traits being used. Unfortunately, although the problem will be made worse by the “wrong” standard, it is the existence of a physical appearance standard, and not its details, that is the danger. The currently proposed standard is flexible enough to appear to cover many of our dogs. In practice, however, an appearance standard, however broad it may seem, will subject the breed to all the problems listed above. Although there is a popular belief that a dog that looks like his father (or mother) will work like his father (or mother) this is simply not necessarily true. Because of recombination of genes, it is no more likely that the pup with his father’s markings is going to behave more like his father than the pup with completely different markings. If we were to set the show standard to duplicate in every detail the appearance of the latest International Supreme Champion, this would no more guarantee us a working breed than any other conformation standard. If we don’t choose the pups that work like the latest Champion, we are not selecting the right genetic blend from the many possible combinations. 8. What Is A Breed? As was stated in the USBCC Spring Newsletter: Currently, we have several registries, here and abroad, organizing the Border Collie breed and directing its selective breeding. They all communicate with each other, their breeding goals are the same, and dogs move freely from one registry to another, so that they are effectively a single genetic population. From the moment the AKC closes its books on the breed they have derived from the existing Border Collie, they will have created a separate genetic population, on which new selective rules will apply. Whatever its origin, and whatever the standard of selection (even if it were to be a performance standard!) this new breed will inevitably begin to differ from the breed registered by the existing registries. It will not be a Border Collie. Reproductive isolation, the genetic separation of one group of breeding animals from another, cannot help but result in two distinct “gene pools,” and thus two different breeds. In natural selection–evolution–this is the path to the formation of separate species. In artificial selection, it is the path to the formation of separate breeds. Even with a very similar standard of performance, two genetically separate populations will eventually diverge simply by the effect of drift, the accidental change resulting from the use of a few sires to produce large numbers of pups. In fact, there can be no other reason for the AKC to close the books and prevent future entry of dogs registered with existing Border Collie registries but this: to create and perpetuate a separate genetic population, i.e., a separate breed of dogs.

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(RxWiki News) Although medical-grade honey has previously shown promising antibiotic properties, it may not live up to the hype for certain infections. A recent study compared topical treatments of honey against a standard wound care for preventing infection at the site of dialysis. They looked for rates of infection and how long it took for an infection to develop. They found that between the honey and the standard care, there was no significant difference in rates of infection. Additionally, more people with the honey treatment reported a negative side effect, like skin irritation. The researchers suggested that honey may not be an effective way to prevent infections from dialysis wounds. "Talk to your doctor about preventing infection." David Johnson, PhD, of the Australian Kidney Trials Network in the University of Queensland led the study in order to see how well honey worked in treating infections that resulted from a certain kind of dialysis treatment. Specifically, he used patients who had experienced kidney failure and were using peritoneal dialysis. When the kidneys fail, they can't filter the blood. In peritoneal dialysis, a catheter is inserted into a patient's abdomen and a solution is used to help filter wastes from the body. Peritoneal dialysis is an important treatment option for people with kidney failure, but it can lead to infection at the insertion site or inside the abdomen. Usually, infections resulting from peritoneal dialysis are treated with antibiotics. However, some bacteria are becoming resistant to the antibiotics used, so the antibiotics are becoming less effective. Some previous reports have suggested that medical grade, sterilized honey may be able to kill bacteria while avoiding promoting antibiotic resistance. This study tested honey in place of antibiotics for some patients undergoing peritoneal dialysis. The researchers used 371 participants who had experienced kidney failure and were being treated with peritoneal dialysis. Of the participants, 186 received a topical treatment of medical-grade honey and standard wound care. The other 185 participants received standard wound care, with mupirocin ointment if they were carriers of nasal S. aureus. Doctors examined the patients and the exit sites of their catheters every two months for up to 24 total months. They were looking to see if the honey treatment delayed the time to infection of the dialysis area. The researchers found that 170 of the 371 participants developed an infection related to peritoneal dialysis: 82 participants who had been treated with honey and 88 who were treated with standard care. They also found that the time it took to develop an infection were not significantly different between the honey group and the control group. Patients in the honey group averaged of 16 months until their first infection, and patients in the control group averaged of 17.7 months until their first infection. Patients with diabetes in the honey group averaged 11.6 months until their first infection. The risk of peritonitis was almost two times as high compared to patients with diabetes in the control group. People in the honey group were also much more likely to withdraw from the study due to a skin reaction. Additionally, there were no differences in serious side effects or death between the honey and control groups. However, people in the honey group were more likely to require hospital admission for removal of part of a parathyroid gland, uterine bleeding, and high blood sugar. The researchers concluded that, in this trial, honey was not an adequate treatment for preventing infections related to peritoneal dialysis. “While the fact that honey doesn’t contribute to antibacterial resistance makes it an attractive option for preventing infection at wound sites, our results suggest that honey cannot be routinely recommended for the prevention of infections related to peritoneal dialysis,” said Prof. Johnson in a press release. The study was published in The Lancet on October 9. The research was funded by Baxter Healthcare, Queensland Government, Combita, and Gambro. Some of the researchers reported financial ties to Baxter Healthcare and other pharmaceutical companies.

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Each type of mining equipment comes with its own set of mining activities. The most common types of mining equipment vary depending whether the work is being carried out above or below ground or mining for gold, metals, coal or crude oil. Chapter 7 COAL If we as a nation are to benefit in the future from our enormous, low-cost coal reserves, a variety of efforts are necessary to (1) develop and demonstrate new "clean coal" Coal. Coal is a naturally occurring combustible material consisting primarily of the element carbon. It also contains low percentages of solid, liquid, and gaseous hydrocarbons and/or other materials, such as compounds of nitrogen and sulfur. Mining Types: Hardrock Mining . Not so often utilized in the 19th century, it is a common practice today, especially with copper and coal. Because this type of mining devastates the landscape, regulations are generally in effect that requires companies to restore the environment when the mining . Coal mining, especially mountaintop removal mining, can damage large areas of land and destroy natural habitats. Higher grades of coal burn more cleanly than lower grades, although they still pollute more than other fuels. Types . Room and pillar mining is the most common method of underground mining. The roof of the mine is supported by areas or columns of coal (pillars) spaced out at regular intervals in rooms from which the coal is mined. The two types of room and pillar mining are conventional and continuous mining. The coal formation process involves the burial of peat, which is made of partly decayed plant materials, deep underground.The heat and pressure of burial alters the texture and increases the carbon content of the peat, which transforms it into coal, a type of sedimentary rock. land is too hilly for surface mining, coal miners must go underground to extract the coal. Most underground mining takes place east of the Mississippi, especially in the Appalachian mountain states and is used to produce about 40 percent of U.S. coal today. Th e type of underground mining technique used is determined by how the coal seam is . Coal mining and coal fueling of power stations and industrial processes can cause major environmental damage. Water systems are affected by coal mining. For example, mining affects groundwater and water table levels and acidity. Nov 25, 2018 · A piece of coal used for burning. Note that in British English either of the following examples could be used, whereas the latter would be more common in American English. Put some coals on the fire. Put some coal on the fire. A type of coal, such as bituminous, anthracite, or lignite, and grades and varieties thereof. Mining is the industry and activities connected with getting valuable or useful minerals from the ground, for example coal, diamonds, or gold. Anthracite: This is the highest ranked, hardest, oldest, and least common type of coal.It possesses a high energy content, high percentage of carbon (>85%) and relatively little moisture or volatiles. Coal mining definition: the act, process, or industry of extracting coal from the earth | Meaning, pronunciation, translations and examples INTRODUCTION TO MINING . A further subdivision of the types of minerals mined by humankind is also common. These terms are often used in the industry to differentiate between . that can be utilized as fuels,such as coal,petroleum,natural gas,coalbed methane,gilsonite,and tar sands. The three main types of surface coal mining are strip mining, open-pit mining, and mountaintop removal (MTR) mining. Surface Mining: Strip Mining Strip mining is used where coal seams are located very near the surface and can be removed in massive layers, or strips. Surface mining, method of extracting minerals near the surface of the Earth. The three most common types of surface mining are open-pit mining, strip mining, and quarrying. See also mining and coal mining. Mining definition is - the process or business of working mines. . Katowice has a long history of coal mining, . 7 Obscure Names and Types of Songs 'Aubade,' 'threnody,' and other songs for the right mood. Ask the Editors. 2018 Word of the Year: Behind the Scenes. The coal is widely used for generating steam power and industrial purposes. Sometimes called "black lignite," sub-bituminous coal is not stable when exposed to air; it tends to disintegrate. This type of coal contains more moisture and volatile matter than other bituminous coal types. What is Coal? Coal is an organic sedimentary rock that forms from the accumulation and preservation of plant materials, usually in a swamp environment. Coal is a combustible rock and, along with oil and natural gas, it is one of the three most important fossil fuels.Coal has a wide range of uses; the most important use is for the generation of electricity. The calorific value of coal varies with percentage of carbon present in it. Coal depending upon variation in percentage carbon, can be divided into three egories as follows (bituminous / anthracite type is the most abundant form present in Indian coal): Table 2.3: Categories of Coal Coal is the largest and most widespread fossil fuel resource providing 23 per cent of the world's energy. However widespread concern about environmental emissions from coal has started to limit . Section 3(h)(1) of the Act defines the term "mine" and includes related milling operations within that definition. Mine development, rehabilitation activities, and exploration work at an established mine are within the Act's scope. All types of mining, including placer, dredge, and hydraulic operations must be . There are two types of room and pillar mining–conventional mining and continuous mining. Conventional mining is the oldest method and accounts for only about 12% of underground coal output. In conventional mining, the coal seam is cut, drilled, blasted and then loaded into cars. The Sun (2009) The obsessive desire to stop burning coal has overwhelmed common sense. The Sun (2016) Coal tar fills your lungs and your head. Times, Sunday Times (2014) The mining of gold and silver was not essentially different from the mining of coal and iron. The life cycle of mining begins with exploration, continues through production, and ends with closure and postmining land use. New technologies can benefit the mining industry and consumers in all stages of this life cycle. This report does not include downstream processing, such as smelting of . The choice of mining method is largely determined by the geology of the coal deposit and its distance to the surface. Underground mining currently accounts for a larger share of world coal production than surface mining. Coal can be burned for heating or to produce electricity. 1.7.3 Marketable Reserves 2. Coal Mining 2.1 Surface Mining 2.1.1 Strip Mining . a brief prospect for coal exploration and mining is given. With the wide range of subjects that have to be covered in an article of this type, the amount of detail that can be included on many aspects is greatly limited. As a coal definition: 1. a hard, black substance that is dug from the earth in pieces, and can be burned to produce heat or power, or a single piece of this: 2. a hard, black substance that is dug from the earth in lumps and used as a fuel, or a single piece of this substance: . Learn more. Fossil fuels are formed from the remains of once-living organisms. Prehistoric plants and animals provided the raw material for the list of fossil fuels that are in use today. Seeing examples of fossil fuels will help you understand the importance of these materials as major sources of energy. Coal-fired power plants provide about 45 percent of U.S. electricity. To increase the percentage of electricity coming from clean energy sources, America will likely have to move away from coal .

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Lunchtime starts at noon at the Jordan Foundation. Nine or ten children are seated in colourful plastic chairs around two tables, happily digging into a full plate of rice and vegetables. Joyce (6), gets up from her chair and walks to the other table to help a smaller boy with his food. She gently wipes his mouth with a napkin. Joyce is partially blind. The other children eat in complete darkness. Twenty-two visually impaired children live here, at the residential centre of the Jordan Foundation in Gasabo, Kigali. A true place of hope for them. In 2015 Mrs Vanessa Bahati and her husband Jean Bosco Hakiza received the devastating news that their third child, Jordan, was born blind and he would never be able to see. Determined to find the best possible care for her son, Mrs Bahati researched organisations and institutions in Rwanda and abroad and she was unhappy with what she found. She realized that for blind children from poor families, the future looked particularly grim and she decided to act. Bahati reached out to other parents with blind children, to counsellors, teachers and authorities, to friends and sponsors. And this is how the Jordan Foundation, named after her son, saw the light Changing the mindset The Jordan Foundation takes care of visually impaired children between the ages of 3-9, who come from poor families in Rwanda. The children are offered a safe place to live and have access to medical care and eye treatment, but also to other health services such as counselling, physiotherapy, and nutrition. Eulade Manzi, one of the coordinators of the Foundation, explains that blind children from villages in remote and poor rural areas are often hidden from the public eye and rejected by their families. The child will not go to school and does not receive proper healthcare. When it is known such a child is there, the specialists from the Jordan Foundation talk to the local authorities and the parents in the hope of raising awareness of the rights of blind children and persuading them to give the child in their care “There is a lot of stigma on blindness”, says Manzi. “Some parents consider these children “useless”. They don’t know how to care for them”. He points at one of the children, a boy of about six years old named Hadi. “Hadi was left behind by his parents on the street. A catholic organization picked him up and brought him to our door when they realised he was blind”, he says. “Parents can visit their children on Sundays, and are invited to regular parent meetings”, Manzi continues, “Our counsellors make every effort to change the parents’ mindset and give them social and economic support so they can accept the child’s disability”. After lunch, Joyce and the other children go outside to play. They laugh and chat like any other kids their age. It is clear that Joyce feels a responsibility because she can see a little bit. She supports the others as they practice walking with a stick. One of the other boys, Jean-Claude (4) wasn’t born blind either but suffered a series of eye infections when he was two years old. The doctors took his eyes in order to save his life and he was brought into the care of the Jordan Foundation. He speaks a little bit of English now and when asked if he minds having his picture taken, he straightens up as if in military position and yells: Cheeeeeese! He is a happy, sociable young boy who likes English songs and music. It is heart-breaking to think what life would have been like for him, and his 21 friends, without the efforts of Vanessa Bahati. A school for the blind The children that are of the right age currently attend the local Gihogwe Primary School, where they receive additional lessons from a special-needs teacher, Mr August Habyarimane. The Jordan Foundation takes care of school fees and materials. During the holidays, most children return to their villages and the Jordan Foundation fights malnutrition by supporting their families with small livestock or training to set up kitchen gardens with seeds. The World Health Organization (WHO) estimates that of the 19 million children that are visually impaired globally, less than 10% of them have access to education, and they are more likely to suffer from malnutrition, abuse, sickness and infant mortality. Vanessa Bahati believes all visually impaired children should have the support, healthcare and education to become independent adults and active citizens. So, her ambition reaches further. At the moment, the Foundation rents the residential centre where the children live, but the building has its limitations and only 22 children can be accommodated. Furthermore, the school is not attached to the centre and transport to and from the school can be a daily issue. Some time ago the Foundation was able to purchase a plot of land in Rutunga, Gasabo district. Bahati’s dream is to build a special school there that can offer a better future to a hundred visually impaired children. The construction ground will be broken on October 19th this year and Bahati is busy raising the funds for its first classrooms, because this is how you realize a vision: step by step. This article was written for the Jordan Foundation magazine, Oct 2018. Photos by author. About the Jordan Foundation Jordan Foundation Rwanda is a non-profit organization serving children with visual impairments (blind and partially sighted). Find out more on Facebook: @jordanfoundationrwanda The East African (06 Jan 2018): A Mother’s blind love paid back in kindness New Times Rwanda (16 Nov 2017): How one woman chose to be the eyes of visually impaired children

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About the Gender Equality Program Achieving gender equality is essential to strengthening democratic governance, human rights, and sustainable development. This fact is reflected in numerous international agreements, including Agenda 2030, in which gender equality is both a standalone Sustainable Development Goal (SDG5) and a recognized pre-requisite for achieving all other objectives. The Americas and Caribbean region is viewed as a global leader in gender equality, with vibrant social movements, advances in women’s representation in national parliaments, and comprehensive legislative frameworks on issues like gender-based violence. However, systemic barriers and harmful social norms continue to disadvantage women and other marginalized groups in this region, as around the world. Parliamentarians -- both women and men -- play a critical role in furthering progress on gender equality. Through their legislative functions and platforms, parliamentarians can contribute significantly by reforming discriminatory laws, strengthening social protections, advocating for gender-sensitive budgeting and oversight mechanisms, and ensuring that gender equality work is well-resourced and informed by women’s needs and perspectives. Parliaments themselves must also be responsive to gender in their internal operations and cultures to create enabling environments for change. ParlAmericas supports parliamentary efforts to advance gender-sensitive legislative action. As a part of our gender equality program we create inclusive working spaces that foster peer-driven exchange of best practices, and provide specialized resources and support to strengthen these efforts. In close collaboration with civil society partners, our gender equality program also promotes women’s political leadership, including that of the next generation of empowered women leaders. Our work is informed by intersectional analysis, recognizing systems of discrimination and privilege that overlap with gender relations. The Inter-American Task Force on Women’s Empowerment and Leadership was announced at the 8th Summit of the Americas (Peru, April 2018). With the objective of contributing to regional progress towards SDG 5 (gender equality), the Task Force serves as a coordination mechanism that reinforces commitments and strategies to advance women’s empowerment and leadership. The Task Force is composed of key inter-American and international institutions working across sectors and at multiple levels.

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Practical Handbook for the Actor Terms in this set (10) Who wrote the introduction to A Practical Handbook for the Actor? In the Job of the Actor section of A Practical Handbook for the Actor there is a quote by J.D. Salinger that states "You were a reader before you were a write." By the same token all actors started out as what? It is the job of the actor to clearly define and list those things that are the actor's responsibility and separate those things that are not. What are the 4 responsibilities of the actor? Voice, analyze script, ability to concentrate, and body Why is it that as an actor, you should never concern yourself with talent? Talent if it exists at all, is completely out of your control. Whatever talent might be, you either have it or you don't, so why waste energy worrying about it? The actor must live truthfully under imaginary circumstances. Acting requires common sense, bravery, and a lot of will. common sense/ bravery/ and a lot of will. What is technique? Technique is knowledge of the tools that maybe used for a certain craft and an understanding of how to apply those tools. What is action? Action is what you go onstage to do, the physical process of trying to obtain a specific goal, often referred to as the objective. What is moment? Moment is what is actually happening in the scene as you are playing it at any given instant. What are the 9 checklist items that an action must have? Be physically capable of being done Be fun to do Have its test in the other person Not be an errand Not presuppose any physical of emotional state Not be manipulative Have a cap Be in line with the intentions of the playwright OTHER SETS BY THIS CREATOR Parts of a Story (POS) The Sandwich Technique Quiz#2- The Sandwich Technique, Parts of a Story, Stage Directions Stage Directions- Proscenium Stage

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Crimen falsi is Latin for “crime of dishonesty.” A conviction for fraud is unique because it is seen as a reflection of a person’s honesty. Fighting these charges often involves going through bank statements, business records, recorded surveillance, and phone records. Below is a list of common fraud charges: -There are several ways to commit welfare fraud when applying for aid or benefits from state or federal programs. Typical cases involve: failing to disclose material facts, failing to report a change in circumstances, altering or forging food stamps or Medicaid card, and receiving unauthorized payments. Fraudulent use or possession of personal identification information: -This is the willful and unauthorized use or possession with intent to use the personal identification information of another without their consent. Organized fraud/Scheme to defraud: -Involves obtaining property through an ongoing, systematic course of conduct with the intent to defraud one or more people. Forgery and Uttering: -Forgery is the falsifying of a document with the intent to defraud another person. Uttering is the passing of such a document knowing it to be forged and with the intent to defraud. Although the facts may arise from a single event, Forgery and Uttering are crimes independent of each other. -This is essentially passing a bad check. This act becomes criminal if the payor knows there are insufficient funds in the account and he knows there is no arrangement with the bank to pay the amount in question. Fraudulent use of a credit card: -Occurs when a person uses a credit card with the intent to defraud for the purpose of obtaining good or services. These cases generally involve credit cards that are stolen or forged.

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Meteorites have traditionally been defined as solid objects that have fallen to Earth from space. This definition, however, is no longer adequate. In recent decades, man-made objects have fallen to Earth from space, meteorites have been identified on the Moon and Mars, and small interplanetary objects have impacted orbiting spacecraft. Taking these facts and other potential complications into consideration, we offer new comprehensive definitions of the terms ``meteorite,''``meteoroid,'' and their smaller counterparts: A meteoroid is a 10-μm to 1-m-size natural solid object moving in interplanetary space. A micrometeoroid is a meteoroid 10μm to 2mm in size. A meteorite is a natural, solid object larger than 10μm in size, derived from a celestial body, that was transported by natural means from the body on which it formed to a region outside the dominant gravitational influence of that body and that later collided with a natural or artificial body larger than itself (even if it is the same body from which it was launched). Weathering and other secondary processes do not affect an object's status as a meteorite as long as something recognizable remains of its original minerals or structure. An object loses its status as a meteorite if it is incorporated into a larger rock that becomes a meteorite itself. A micrometeorite is a meteorite between 10μm and 2mm in size.Meteorite-``a solid substance or body falling from the high regions of the atmosphere'' (Craig 1849); ``[a] mass of stone and iron that ha[s] been directly observed to have fallen down to the Earth's surface'' (translated from Cohen 1894); ``[a] solid bod[y] which came to the earth from space'' (Farrington 1915); ``A mass of solid matter, too small to be considered an asteroid; either traveling through space as an unattached unit, or having landed on the earth and still retaining its identity'' (Nininger 1933); ``[a meteoroid] which has reached the surface of the Earth without being vaporized'' (1958 International Astronomical Union (IAU) definition, quoted by Millman 1961); ``a solid body which has arrived on the Earth from outer space'' (Mason 1962); ``[a] solid bod[y] which reach[es] the Earth (or the Moon, Mars, etc.) from interplanetary space and [is] large enough to survive passage through the Earth's (or Mars', etc.) atmosphere'' (Gomes and Keil 1980); ``[a meteoroid] that survive[s] passage through the atmosphere and fall[s] to earth'' (Burke 1986); ``a recovered fragment of a meteoroid that has survived transit through the earth's atmosphere'' (McSween 1987); ``[a] solid bod[y] of extraterrestrial material that penetrate[s] the atmosphere and reach[es] the Earth's surface'' (Krot et al. 2003).

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As summer draws to a close, we’re all getting into the swing of back to school! Shopping for new supplies and getting ready for upcoming soccer games are both important, but making sure your child gets to school with a nutritious lunch is crucial to their ability to focus and learn. However, if your child has braces, making sure lunch is both healthy and braces-friendly can be difficult. Fear not—small adjustments to a child’s school lunches can ensure nutritious, safe options. Eggs, seafood, and chicken are easy ways to provide your child with protein without damaging his or her teeth. Your child can get calcium from yogurts and puddings, and their daily intake of fruits with soft ones such as tangerines, oranges, or kiwis. Steamed vegetables are an excellent option as well. A healthy lunch might include a soft sandwich, paired with a soft, peeled fruit (think orange or banana), and a small treat, like pudding or applesauce. Hard foods, such as pizza crust, should not be in your child’s lunchboxes. If possible, harder foods can be safe if they are cut up into small pieces to prevent any damage to braces. Apples, pears, and other hard, crunchy fruits should be cut up as well. If your child bites into hard foods while wearing braces, the brackets can easily pull away from teeth and break, which can be incredibly painful. By putting careful thought into what your child eats, you can save the time and money it would take to repair damaged brackets. As a general rule of thumb, avoid any foods you consider hard or chewy. Hard candies or gooey caramels are a nightmare for braces, and breakages they might cause can extend the needed time for braces to stay on. So be sure to pack braces-friendly desserts for your kids like soft chocolates, brownies (without nuts) and soft cookies. Be thoughtful about those school lunches and it will all be worth it once a beautiful smile is in place!

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Tennis Psychology - The foundation of Winning Tennis It is based on general and sports psychology and then applied to tennis specifically. There are many common elements in the psychology of tennis which can be found in other sports too. An athlete that wants to perform at his peak needs to learn: Negative thinking affects players much more than they are aware of. It affects body abilities in two ways - being aware of them (feeling tension) and being unaware (the pendulum experiment); moreover it evokes negative feelings - emotions that cloud the player's judgment and affect his body abilities - again. By being more and more aware of what he is thinking a player can then change his thoughts to a more positive and solution based thinking. The awareness of our thoughts is quite a challenge in the tennis psychology approach. A player's arousal can be too high or too low and in both cases he is not able to play his best tennis. Arousal affects his body and mind abilities - a player may have too much muscle tension and his decisions are usually not tactically intelligent. Learning to find the "ideal state" is the key in controlling one's arousal and one of the most important aspects of tennis psychology. A player may get upset (and it happens often) about an event that he cannot control or even influence. For example - the noise of the planes flying over the court, windy conditions, court conditions, his opponent's luck and so on. By being focused on these events he wastes his energy which could be used on elements that he can control - his attitude and effort, how he intends to play, … Many players start the match with good concentration but they drop their level of concentration because of disturbing outside events, pressure situations, emotional reactions to various events and so on. A player needs to learn how to quickly and effectively refocus to be able to play his best tennis. Imagery or visualization is extremely useful in almost all aspects of the tennis game. A player can improve technique, strategy, physical abilities and his mental preparation of certain events. Another use of imagery is when a player misses a shot and then quickly sees in his mind how he hit the ball correctly. Using imagery is an incredibly efficient technique, not only in tennis sports psychology but in everyday life too. Confidence is one of those elements where tennis psychology can help really quickly and with very simple tools. A player who is not confident will hesitate in his decisions, will be afraid to take risks and his shots will usually miss by just a little. Doubt can be seen in reality as small misses that happen regularly. When a player builds his confidence he is able to play at his best and doesn't lose his hope when a big challenge appears. Limiting beliefs are one of the most limiting and troublesome aspects of human's psyche. They are mostly deep in the subconsciousness and are sometimes hard to find. A limiting belief for example is when a player believes that he is not good in tie-breaks and he will then self-sabotage himself in those crucial moments to prove himself right. Having no limiting beliefs means that the player is in total acceptance of everything that happens. Outside events are just events with no meaning. Tennis psychology helps the player to accept and deal with them. There are three main principles of the Inner Game - quieting the mind, non-judgment and trusting the body. The player must first learn to apply them in training. And when he experiences these effects in training he knows what to look for in the match. He then plays the inner game - how to perform at his peak. These are the fundaments of tennis psychology and by understanding these principles and applying them daily a player develops mental toughness. He knows how to apply the tools and as a very positive side effect gains a lot of self confidence. He now knows that he has ways of dealing with his own mind and that most of his competitors do not. He is aware that he has the edge in the most stressful situations in the match and that gives him self confidence. By constant application of these tools a player becomes more and more proficient with them and finds his ideal mental state very quickly if he happens to lose it. These losses of ideal state happen less and less often.

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Figure 8-11.--Drilling in the horizontal boring mill. provides the rotary motion for the tools mounted in the boring bar. Align the work with the axis of the boring bar and bolt and/or clamp it to the table. In the To set the horizontal boring machine for a line cutting operation, the spindle usually moves while the boring operation, insert a boring bar into the spindle work is held stationary. However, there may be times and pass it through the work. The boring bar is when you need to hold the bar in a fixed position and supported on the foot end by the backrest assembly. move the table lengthwise to complete the operation. Depending on the size of the bore, you can use either standard or locally manufactured tooling. The head Figure 8-12.--Boring bar driven by the spindle and supported in the backrest block.

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Avocado is known for being a great source of good fats. Originally from Mexico, contains about 322 calories and 29 grams of fat. Avocados can undoubtedly be considered as fat fruit, but not in a harmful way. Studies have shown that avocado can definitely be included in your daily diet as it can encourage weight loss and health of the whole body. It regulates cholesterol levels Scientists claim that increasing the intake of avocado can regulate cholesterol levels in the body. One study found that daily consumption of avocado in a period of five weeks can reduce cholesterol levels to 13.5mg / dl. It is enough to significantly reduce the risk of heart disease. It helps to reduce waist circumference Avocados are an excellent source of monounsaturated fatty acids and oleic. They can help reduce abdominal fat, which can help reduce the risk of developing metabolic syndrome, a number of health conditions associated with weight gain. A diet rich in monounsaturated acids may prevent the distribution of fat around the abdomen. In contrast to the extra virgin olive oil, avocado oil has a high degree of combustion. This means that you can use in the preparation of food at high temperature. Improve the quality of your diet Avocados are an excellent source of vitamins and a number of other important nutrients that can reduce the volume of your waist. In one study it was shown that avocado enhances the absorption of carotenoids, antioxidant compounds that may help prevent cancer cells. Specifically, avocados can improve the absorption of carotenoids as much as 3 to 5 times better. To include avocado in the daily diet, you can start to use avocado oil. Experts suggest that you use it as a condiment for salads. It reduces the level of free radicals Free radicals attack your mitochondria, and that is sabotaging your metabolism. Free radicals cause a series of chain reactions in the body that destroy cells and DNA, and cause many other health problems. The antioxidants from fresh fruits and vegetables can help to neutralize free radicals, but can not reach the mitochondria and there is a problem. When your mitochondria are not working properly, it affects the metabolism. Studies have shown that monounsaturated acid from avocados can help mitochondria to defend themselves from attack by free radicals. One tablespoon of avocado can help reduce cravings for snacks, and studies have shown that people who eat a moderate daily craving avocados feel as much as 40% less craving for snacks, which usually occurs in the afternoon. It reduces the craving for sweets Avocado for body provides nearly 20 vitamins, minerals and phytonutrients that are important for weight control. Avocado contains about 14 grams of fiber and an excellent source of vitamin K, which helps regulate the degradation of sugar and your insulin sensitivity. One study showed that people who bring a satisfactory amount of vitamin K, a 19% lower risk of developing diabetes over the next 10 years.

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AI::FANN::Evolving::Experiment - an experiment in evolving artificial intelligence Constructor takes named arguments, sets default factory to AI::FANN::Evolving::Factory Getter/Setter for the workdir where AI::FANN artificial neural networks will be written during the experiment. The files will be named after the ANN's error, which needs to be minimized. Getter/setter for the AI::FANN::TrainData object. Runs the experiment! The optimal fitness is zero error in the ANN's classification. This method returns that value: 0. Returns a function to compute the error. Given an argument, the following can happen: 'sign' => error is the average number of times observed and expected have different signs 'mse' => error is the mean squared difference between observed and expected CODE => error function is the provided code reference

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Bilirubin is the water-soluble pigment excreted in the bile. It is a yellow to orange bile pigment produced by the breakdown of Heme and reduction of biliverdin, it normally circulates in plasma and is taken up by liver cells and conjugated to form bilirubin diglucuronide. Failure of the liver cells to excrete bile, or obstruction of the bile ducts, can cause an increased amount of bilirubin in the body fluids and lead to obstructive jaundice. Related Jornals of Bilirubin Journal of Hepatitis, Air & Water Borne Diseases, Immunological Techniques in Infectious Diseases, Infectious Diseases & Therapy, Foodborne pathogens and disease, Infectious Diseases and Diagnosis, Emerging infectious diseases, Viruses, American journal of infection control, Disease markers, Infection, Infectious disease clinics of north America

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| Abstract|| | Background: Children of people with alcohol dependence (COAs) are at high risk for behavioral and cognitive problems. Aim: Aim of this study was to compare the nature and extent of these problems in children of men with and without alcohol dependence. Materials and Methods: 32 children (17 in study group and 15 controls) were evaluated for psychopathology, neurodevelopment, cognitive functioning and family environment. Tools used were: Socio-demographic data sheet, Malin's Intelligence Scale for Indian Children (MISIC), Child Behavior Checklist, Trail Making Test, Neurodevelopment Scale and the Family Environment Scale. Results: Children of men with alcohol dependence had higher externalizing than internalizing scores. Children of alcohol-dependent fathers had higher scores on the neurodevelopment scale and lower scores on the performance scale of the MISIC than the children in control group. These children also made more errors on the Trail Making Test. The family environment of COAs was characterized by lack of independence for its members, greater perceived control and lack of adequate cultural and intellectual activities. Conclusion: Our findings suggest that children of men with alcohol dependence have difficulties with frontal lobe functions and neurodevelopmental tasks. There are also difficulties in the family, which are related to alcohol consumption by the father. Keywords: Alcohol dependent fathers, children, family environment, neurodevelopment, psychopathology |How to cite this article:| Raman V, Prasad S, Appaya M P. Children of men with alcohol dependence: Psychopathology, neurodevelopment and family environment. Indian J Psychiatry 2010;52:360-6 | Introduction|| | Parental mental illness and its impact on the development and behavior of children has been an active field of research over the last two decades. Children of parents with alcohol dependence syndrome are particularly at high risk for substance use as well as other emotional and behavioral problems such as learning disability, hyperactivity, psychomotor delays, somatic symptoms and emotional problems. There have been attempts to study various aspects of children of people with alcohol dependence from India and some published literature is available that looks at various domains in the same sample. ,,, Cantwell's review of prior research indicated that families of hyperactive children have increased prevalence of alcohol-dependent and sociopathic fathers. Six of the seven studies of parents who were alcohol dependent found some association with child hyperactivity. Other childhood conduct problems have also been found such as lying, stealing and truancy. ,, Adolescents who abused alcohol reflected a 46% of parent alcoholism, that is, in 46% of adolescents who abused alcohol, there was family history of alcoholism in the parent/s. , There was an increased prevalence of physical aggression and low anxiety and this best distinguished sons of male alcohol dependents from normals. Another study concluded that central nervous system hyperexcitability may be etiologically linked to the excess of externalizing behaviors observed in this population, which is thought to be a predisposition to a higher risk of developing early onset alcoholism. Lieberman, in a review, states that children of alcoholics are two to ten times more likely to develop alcoholism than children of non alcoholics. Children with relatives who abuse or are dependent on alcohol apparently have a slightly higher risk for drug abuse or dependence than those without relatives who consume alcohol. Evidence from twin and adoption studies has highlighted the significance of genetic influences, and the heritability of alcoholism has been estimated at 40-60% Risk factors that mediate the increased vulnerability and protective factors which moderate the risk included in this review are parental antisocial personality disorder, externalizing behavior, internalizing symptoms, differential response to the effects of alcohol and positive and negative alcohol related expectancies. Neuropsychological functions in these children have been the focus of attention over the last decade. Pihl and Brice reviewed studies of cognitive functioning in children of alcoholics. They found that these children have lower verbal intelligence, overall poor verbal skills, poor verbal and nonverbal memory and poor abstraction and planning. Corral found that children with multi-generational alcoholism, but not children with a father who was alcohol dependent, showed reduced performance in specific cognitive areas such as attention, visuospatial abilities and frontal lobe functions. Studies have also reported reduced visual event related potential (ERP) amplitudes in young males at high risk for alcoholism. In one study, however, authors found that ERP deviations are not attributable to stages of visual processing deficits but represent difficulty involving more complex utilization of information. In a comparison of amplitudes and topography of the P300 generated in response to a visual task, between subjects at high risk (offspring of treatment seeking patients with alcohol dependence) and those at low risk for alcoholism (alcohol naοve individuals with absence of family history of alcohol dependence in any of the first- or second-degree relatives) and its relation to externalizing behaviors, Silva and others found that high risk subjects have lower P300 amplitudes over frontal brain areas. They found that differences are greater in young, tending to converge with increasing age. They also described a strong association between this reduced brain activation and an excess of externalizing behaviors in high risk individuals. The authors concluded that a maturational lag in brain development, causing central nervous system disinhibition and externalizing behaviors may underlie the susceptibility to alcoholism. The highest risk for developing alcoholism exists for individuals who start using alcohol as adolescents, have a high family loading for alcohol problems and display a cluster of behavior traits described as disinhibited, undercontrolled or impulsive, which are usually evident in childhood and persist into adulthood. , On the Child Behavior Checklist (CBCL), Christiansen found that in 103 Danish children of alcohol-dependent fathers, there was a significantly greater incidence of symptoms on 17 of the 118 CBCL items. These authors found that daughters of alcohol-dependent fathers were more impaired than sons of alcohol-dependent fathers on most CBCL measures. In a series of investigations, a positive association has been reported between parental alcoholism and impaired emotional functioning of offspring. Rodriguez Holguin found, in his study, that when compared to controls, children of alcoholics had smaller middle latency auditory evoked potential which the authors opine points to an anomalous pattern of information transmission from the thalamus to cortex. Rao found that alcoholism was present in parents of malnourished (49.4%) and injured children (45%). In another study, Stanley and Vanitha investigated the manifestation of self-esteem and adjustment in a group of 50 adolescent children of alcoholic parents and a matched reference group of adolescent children of non-alcoholic parents. The data revealed lower self-esteem and poor adjustment in all the domains studied in the adolescent children of alcoholic parents than the controls. These deficits, the authors opined, can be attributed to the increased stress and vitiated alcohol complicated domestic environment of the children of alcoholic parents. This study made a strong case for psychosocial intervention for these children. The review of available literature indicates that children of parents with alcohol dependence are at risk for a wide range of neuropsychological dysfunction and psychopathology. This study was an attempt to examine the broad areas of dysfunction in children of fathers with alcohol dependence in the Indian context so that early identification and intervention can be planned. | Materials and Methods|| | This study attempted to look at psychopathology, cognitive functioning and family environment in a group of children of men with alcohol dependence and compared them with a control group of children of men without alcohol dependence. The study was approved by the Hospital Ethics Review Board. Informed consent was taken in writing from all the parents of the children who participated in this study. The study was conducted in the Department of Psychiatry attached to a tertiary care general hospital. The sample was obtained through referral by one of the co-authors. The patients - both in-patient and out-patient - diagnosed as Alcohol Dependence Syndrome according to ICD 10 criteria (WHO, 1992) and who had children aged between 5 and 9 years (as the Neurodevelopmental Examination is standardized for this population) - both male and female - were included in the study. A control group from the pediatrics out-patient department and the school setting was taken with no parental psychiatric illness and mother scoring less than 4 on the General Health Questionnaire (GHQ). The inclusion criteria for children were: father diagnosed as Alcohol Dependence Syndrome; having no other known psychiatric illness; aged between 5 and 9 years; with mother having GHQ scores less than 4 and living with the index parent for at least the preceding year. The exclusion criteria were: parent having any known organic brain syndromes, mental retardation or any other psychiatric illness, children having any known visual/auditory handicap, children with known chronic medical illness like diabetes, asthma or chronic renal disease. All the assessments were done by the first and second authors who were blind to the clinical status of the father. Subjects for the study were referred by the third author from the out-patient and in-patient services. First, for both the groups, the mother was screened using the GHQ (Goldberg) for psychopathology. Children whose mothers scored above the cut-off on the GHQ were excluded from the study. The fathers in the study group were then administered the Severity of Alcohol Dependence Questionnaire (SADQ) by the second author. The assessments involving the parents, the CBCL and the Family Environment Scale (FES), were administered by the second author and the assessments involving the child, Malin's Intelligence Scale for Indian Children (MISIC), Neurodevelopmental Examination, and Trail Making Test (TMT), were administered by the first author. The GHQ is a symptom and well-being scale that serves as a screening for psychopathology. It is a self-rating scale with the severity of symptoms compared to the habitual state of the person in question on a 4-point rating scale. It has sensitivity and specificity of 80-90% in relation to interview-based diagnosis. The 28-item version was used in this study. The SADQ is a short, easy to complete, self-administered 20-item questionnaire designed to measure severity of dependence on alcohol. There are five subscales with four items in each: Physical withdrawal, Affective withdrawal, Withdrawal Relief Drinking, Alcohol Consumption and Rapidity of Reinstatement. Each item is scored on a 4-point scale, ranging from "Almost Never" to "Nearly Always", resulting in a corresponding score of 0-3. Thus, the total maximum score possible is 60 and the minimum is 0. Test-retest reliability of this instrument is 0.85 and factor analysis yields single main factor accounting for 53% of variance. The mother was interviewed by the co-author using a socio-demographic data sheet (developed for the study), the CBCL (Achenbach and Edelbrock) and the FES (Moos). The CBCL is a descriptive instrument designed to classify behavioral and emotional disorders of children aged 4 through 16 years comprehensively. Each of the 113 items is scored on a 3-step response scale: 0, not true; 1, sometimes true; and 2, often true. The test can be self-administered or administered by an interviewer. The two broad band groupings of behavioral problems assessed correspond to the internalizing and externalizing behavior. Adequate reliability and validity has been established by the authors. The FES assesses the social environments of families along 10 salient dimensions. It focuses on measurement and description of the interpersonal relationships among family members, on the directions of personal growth emphasized within the family, and on the basic organizational structure of the family. The FES significantly discriminates among families, is sensitive to parent-child differences in the way in which families are perceived, is related to family size and drinking patterns and discriminates between psychiatrically disturbed and matched "normal" families. This scale has a reliability of 0.67 and the validity of this tool has been established. The author then assessed the children on the MISIC (Indian adaptation of the Wechsler's Intelligence Scale for Children, Malin). This scale is used widely in testing the intelligence in children of age between 5 and 16 years. It provides a Full Scale IQ, a Verbal IQ and a Performance IQ. The reliability and validity of this instrument is well established. The TMT (Luria) was then administered. This is a test of controlled attention and is widely used as a screening device, a test of laterality: a test of perceptuo motor functions and is a sensitive measure of frontal dysfunction. The test consists of a set of numbers (1-16) and alphabets (A-P) randomly spread on a sheet of paper. The child is asked to alternate between alphabetical and numerical sequence (1-A, 2-B, etc.). The total time taken and the number of errors made are recorded. The TMT has been found to have a high reliability (0.81) and adequate validity. The final test done with the children was the Neurodevelopmental Examination (Lindahl et al.). This test is used in children of age between 5 and 9 years. This examination consists of 21 tasks. This ranges from an evaluation of the child's auditory and visual acuity to threading wooden beads within a time limit. It is a sensitive indicator of neurological compromise and is known to pick up subtle deficits. Each item was scored 0, 1 or 2: 0 score if normal, 1 if uncertain or mildly abnormal and 2 if abnormal. The maximum score is 40 and a score of 8 and above is considered significant and indicates dysfunction. The test-retest reliability coefficient of this instrument is established at 0.78. All the data obtained were analyzed after loading on to SPSS and using the student's "t" test. A comparison of all the parameters - psychopathology, cognitive functions and family environment - was made between the study group and the control group. | Results|| | Forty-three children were screened for the study. During the screening procedure, a number of children (n=11) had to be excluded. The reasons were: child having had no formal education (n=4), child unable to come for completing the assessment (n=2) and mothers scoring high on the GHQ (n=5). Out of 32 children included in the study, 17 (8 boys and 9 girls) were in the study group and 15 (6 boys and 9 girls) were in the control group. The sample was restricted by the time frame available for the study. As can be seen in [Table 1], there were no significant differences between the two groups with respect to age of the child. [Table 2] also reveals no differences between the two groups with respect to sex of the child. The scores on the CBCL were analyzed on the basis of the two scales - Internalizing Scale and Externalizing Scale. [Table 3] shows the scores obtained by the two groups on the two scales of the CBCL. As can be seen from the table, the children of alcohol-dependent parents obtained statistically significant high scores on the externalizing scale and a marginal, though not statistically significant, high score on the Internalizing Scale. [Table 4] contains the scores obtained on the Neurodevelopmental Examination. There is a statistically significant difference between the two groups on the Neurodevelopmental Examination, with children of alcohol-dependent parents scoring higher, indicating more difficulty with neurodevelopmental tasks. Neuropsychological functioning in terms of general intelligence and perceptuo motor skills was assessed using the MISIC and the TMT. The results of these two tests are presented in [Table 4]. |Table 4 :Scores obtained by the two groups on the neuropsychological tests – Neurodevelopmental| Examination, Malin's Intelligence Scale for Indian Children and Trail Making Test Click here to view As can be seen from the table, there is a statistically significant difference between the two groups on the Verbal, Performance as well as Full scale IQ scores on the MISIC. In the TMT, there was a statistically significant difference between the two groups in the terms of the errors made - children of alcohol-dependent parents made more errors although they took a similar amount of time to do the task. The results are presented in [Table 4]. [Table 5] presents the data obtained from the FES. Families of alcohol-dependent parents had lower degrees of independence for its members, fewer cultural/intellectual activities and greater degree of perceived control. |Table 5 :Scores obtained by the two groups on the various subscales of the Family Environment Scale| Click here to view | Discussion|| | The results can be discussed by answering three broad questions: - Behaviorally, are children of alcohol-dependent fathers different from children of non-alcohol-dependent fathers? - Do children of alcohol-dependent fathers have difficulties with cognitive tasks? - Are family environments in families with an alcohol-dependent father different from normal families? There were no age or sex differences between the two groups. 1. In this study, we used the CBCL as a tool for assessment of behavioral problems. We found that there were no significant differences between the two groups on the Internalizing subscale. On the Externalizing subscale, there was a statistically significant difference between the two groups. Other authors have also found, with larger samples, that children of alcohol-dependent parents, especially daughters of alcohol-dependent parents, scored higher than controls on the CBCL - both on the Internalizing and Externalizing Scales. ,, In Indian literature too, studies have shown that there is higher externalizing behavior in children who are at high risk for alcohol dependence compared to those at low risk. Behavioral and emotional difficulties are commonly seen in children of alcohol-dependent parents and substantive findings exist in literature. Even with a small sample, our data Corroborates this. It was found that children had particular difficulties with handling frustration, were irritable and overall described by parents as children needing extra supervision. This is an issue that can be due to both intrinsic as well as extrinsic reasons. Genetic studies have shown that children of alcohol-dependent fathers tend to be temperamentally more difficult from infancy and disciplining patterns also tend to be inconsistent in such families. This causative link needs further exploration. 2. To assess cognitive functioning, we used several unrelated and probably overlapping measures. The 'Neurodevelopmental Scale' has been used previously to assess gross cognitive dysfunction in children at risk (having various neonatal problems particularly low birth weight and preterm babies). In this study, we used this measure as a gross indicator of cognitive functioning. This scale has shown significant differences between the children of alcohol-dependent parents and normals, with the children of alcohol-dependent parents scoring higher (higher scores indicate greater difficulty with neurodevelopmental tasks). This is an interesting finding as most studies in this area have looked at specific skills. ,,, Although this is a gross indicator, the fact that a significant difference was found even on this scale reflects the nature and extent of the deficits. The TMT, a test of controlled attention, is a sensitive measure of frontal dysfunction. In this test, two aspects were considered - the time taken and the errors made. As can be seen from the data, there were significant differences between the two groups, that is, children of alcohol-dependent parents took as much time to do the task as the control group but tended to make more errors and this difference is statistically significant. This decision of choosing speed over accuracy is a function of the frontal lobe and frontal dysfunction is well known in children of alcohol-dependent parents. ,,, Our study proves this as well. In addition, as seen on the CBCL, impulsivity was also found to be a significant factor differentiating children of alcohol-dependent parents from normal children. This impulsivity may also be reflected in the choice of doing a task quickly rather than accurately. On the MISIC, there is a statistically significant difference on the Verbal, Performance and Full Scale IQ with children of alcohol-dependent parents obtaining lower scores than normal controls, indicating a global dysfunction. Assessment of cognitive dysfunction using the Wechsler scales has shown significant differences in previous studies as well. The reason for this has been discussed in some studies - some explanations are related to the general level of stimulation at home, some to the educational level of parents, some to more basic neuropsychological dysfunction. This study, however, is based on a small sample and cannot make causative links but this is an area that needs further research. 3. There have been a number of studies focusing on various aspects of family environment. ,, We found, in our study, that statistically significant differences were present on several aspects of family functioning. In the families where the father was alcohol dependent, there appeared to be decreased independence for its members, fewer opportunities for cultural and intellectual activities and there was a greater degree of perceived control when compared to normal families. The lack of independence and the greater degree of perceived control are obviously linked. Family members may feel dictated to. This has also been a finding by other authors , who reported that fathers would be aggressive, impose their will on others and did not tolerate non compliance especially in the family context. The other dimension where there is a significant difference between the families of alcohol-dependent parents and normal controls is the dimension of cultural and intellectual activities. This has not been discussed in many studies. It appears, in our study, that family members felt that fathers who were alcohol dependent were not available for family rituals and social interactions. Drinking related behaviors may take precedence over other activities. This is definitely an area where children and their mothers have reported, in our study, to be of some concern to them. Therefore, this seems to be an area that will need clinical attention to ensure that families' coping styles are adaptive. This is discussed in some detail in another study from India. Therefore, this adds to an extensive body of literature showing that there is increased psychopathology in the form of increased externalizing behavior, difficulties in neurodevelopment and frontal lobe functions and some differences in the family environment in children and families of alcohol-dependent fathers when compared to normal controls. | Conclusions|| | There is enough evidence in literature to indicate that children in families where there is an alcohol-dependent father are at increased risk for behavioral and emotional problems, cognitive deficits and dysfunctional family environment. Our study endorses these findings in the Indian context. In addition, this is a group at risk and preventive strategies in the form of early assessment and intervention for possible problem areas would definitely be helpful. | References|| | |1.||Rao KN, Begum S, Venkataramana V, Gangadharappa N. Nutritional neglect and physical abuse in children of alcohol dependent parents. Indian J Pediatr 2001;68:843-5. | |2.||Silva MC, Benegal V, Devi M, Mukundan CR. Cognitive deficits in children of alcoholics: At risk before the first sip! Indian J Psychiatry 2007;49:182-8. | |3.||Muralidharan K, Venkatasubramanian G, Pal PK, Benegal V. Abnormalities in cortical and transcallosal inhibitory mechanisms in subjects at high risk for alcohol dependence: A TMS study. Addict Biol 2008;13:373-9. | |4.||Stanley S, Vanitha C. Psychosocial correlates in adolescent children of alcoholics- Implications for intervention. Int J Psychosoc Rehabil 2008;12:67-80. | |5.||Cantwell D. Familial - genetic research with hyperactive children. In: Cantwell D, editor. The hyperactive child: Diagnosis management and current research. New York: Spectrum; 1975. p. 93-105. | |6.||Steinhausen HC. Children of alcoholic parents. A review. Eur Child Adolesc Psychiatry 1995;4:143-53. | |7.||West MO, Prinz RJ. Parental alcoholism and childhood psychopathology. Psychol Bull 1987;102:204-18. | |8.||Sher K, Walitzer KS, Wood PK, Brent EE. Characteristics of children of alcohol dependent parents: Putative risk factors, substance use and abuse and psychopathology. J Abnorm Psychol 1991;100:427-48. | |9.||Rydelius PA. Are children of alcohol dependent parents a clinical concern for child and adolescent psychiatrists of today? J Child Psychol Psychiatry 1997;38:615-24. | |10.||Schukit MA, Smith TL, Radziminski S, Heyneman EK. Behavioural symptoms and psychiatric diagnoses among 162 children in non alcoholic or alcoholic families. Am J Psychiatry 2000;157:1881-3. | |11.||Lieberman DZ. Children of alcohol dependent parents: An update. Curr Opin Pediatr 2000;12:336-40. | |12.||Enoch MA, Goldman D. Genetics of alcoholism and substance abuse. Psychiatr Clin North Am 1999;22:289-99. | |13.||Pihl RO, Brice KR. Cognitive impairment in children of alcohol dependent parents. Alc Health Res World 1995;19:142-7. | |14.||Corral MM, Holguin SR, Cadaveira F. Neuropsychological characteristics of children of alcohol dependent parents: Familial density. J Stud Alcohol 1999;60:509-13. | |15.||Steinhauer SR, Locke J, Hill SY. Vigilance and iconic memory in children at high risk for alcoholism. J Stud Alcohol 1997;58:428-34. | |16.||Haber JR, Jacob T, Heath AC. Paternal alcoholism and offspring conduct disorder: Evidence for the 'common genes' hypothesis. Twin Res Hum Genet 2005;100:652-661. | |17.||Begleiter H, Projesz B. What is inherited in the predisposition toward alcoholism? A proposed model. Alcohol Clin Exp Res 1999;23:1125-35. | |18.||Christensen HB, Bilenberg N. Behavioral and emotional problems in children of alcoholic mothers and fathers. Eur Child Adolesc Psychiatry 2000;9:219-26. | |19.||Anderson E, Quast W. Young children in alcoholic families: A mental health needs assessment and a prevention strategy. J Prim Prev 1983;3:174-87. | |20.||Rodriguez Holguin S, Corral M, Cadaveira F. Middle latency auditory evoked potentials in children at high risk for alcoholism. Neurophysiol Clin 2001;31:40-7. | |21.||World Health Organization. Classification of Mental and Behavioural Disorders (ICD -10). Clinical descriptions and diagnostic guidelines. Geneva: WHO; 1992. | |22.||Goldberg D. The determination of psychological illness by questionnaire. London: Oxford University; 1972. | |23.||Stockwell T, Murphy D, Hodgson RJ. The severity of alcohol dependence questionnaire: Its use, reliability and validity. Br J Addict 1983; 78:145-55. | |24.||Achenbach TM, Edelbrock ES. Manual for the Child Behaviour Checklist and Revised Child Behaviour Profile. USA: Queen City Printers Inc; 1993. | |25.||Moos R. Family Environment Scale and Preliminary Manual. 577 College Avenue, Palo Alto, California: Consulting Psychologists Press; 1976. | |26.||Malin AJ. Malin's intelligence scale for Indian children (MISIC). Indian J Ment Retard 1976;4:15-25. | |27.||Luria AR. Higher cortical functions in man. New York: Basic Books; 1980. | |28.||Lindahl E, Michelsson K, Helenius M, Parre M. Neonatal risk factors and later neurodevelopmental disturbances. Dev Med Child Neurol 1988;30:571-89. | Department of Psychiatry, St. John's Medical College Hospital, Bangalore - 560 034 Source of Support: Project funded by the St. Johnís Research Society, Conflict of Interest: None [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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Sentence 003 Let the cat out of the bag Leslie: Which of the three Sentences is incorrect? Flora: ’It rained a lot this season.’ F: Because there is a Time Marker in the Sentence: ’this season’ and it is Non-Past. The Sentence is ’It rained a lot this season.’ and it is Past Simple Tense. The Time and Tense don’t agree. L: You are right. The Time is Non-Past and it is manifest, i. e. it is clear to see or understand through the Time Marker. The Time makes the Tense and Non-Past Time can only make Non-Past Tense. Is this Sentence the worst? F: No. There is an even worse Sentence here and it is ’It raining a lot this season.’ L: Why is it worse than the previous Sentence? F: Because it is not a Sentence. L: Why do you think so? F: Because it has no Verb. ’Raining’ is not a Verb. If there is no Verb, there is no Sentence. L: Then, we have found the correct Sentence. Can you help me? F: Yes, and it is ’It has rained a lot this season.’

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The Malankara Church is a church of the Saint Thomas Christians of Kerala, India, with particular emphasis on the part of the community that joined Archdeacon Mar Thoma in swearing to resist the authority of the Portuguese Padroado in 1653. This faction soon entered into a relationship with the Syriac Orthodox Church of Antioch, and was thereafter often known as the Malankara Syrian Church. As part of the Saint Thomas Christian community, the church traced its origins to the evangelical activity of Thomas the Apostle in the 1st century. As an independent faction, it originated in the first major split within the Saint Thomas Christian community. Historically, the Thomas Christians had been united in leadership and liturgy, and were part of the Church of the East, based in Persia. However, the collapse of the Church of the East's hierarchy in Asia left the province of India effectively isolated, and through the 16th century, the Portuguese, recently established in Goa, forcefully drew the Thomas Christians into Latin Rite Catholicism. Resentment of these measures led the majority of the community to join the archdeacon, Thoma, in swearing never to submit to the Portuguese in the Coonan Cross Oath. Several months later Thoma was ordained as the first indigenous Metropolitan of Malankara. Following the Oath, in 1661 Pope Alexander VII established a new East Syrian Rite hierarchy in communion with Rome for the Saint Thomas Christians; by the next year 84 of the 116 communities had joined, forming what is now the Syro-Malabar Catholic Church. The remaining 32 communities stayed independent, and formed a relationship with the Syriac Orthodox Church. Over the next centuries this relationship strengthened, and the Malankara Church adopted a variant of the West Syrian Rite known as the Malankara Rite (as opposed to the previous East Syrian usage) and entered into full communion with the Syriac Orthodox Patriarch of Antioch. However, through this time the church experienced a series of splits, resulting in large numbers of followers breaking away. In 1772 a Syriac Orthodox bishop consecrated Kattumangatt Kurien (Mar Cyril) as his successor against the wishes of the Metropolitan, Mar Dionysius I; Cyril led a faction that eventually became the Malabar Independent Syrian Church. In the 19th century, a reform movement inspired by British missionaries led to the formation of the independent Mar Thoma Syrian Church, while the rest of the church, resistant to British influence, came under the direct jurisdiction of the Syriac Orthodox Patriarch in 1876. In 1912, a dispute over authority between supporters of the Metropolitan and supporters of the Patriarch finally divided the Malankara Church, with the former group becoming the essentially independent Malankara Orthodox Syrian Church under the Catholicos of the East and the latter maintaining ties with the Patriarch as the Jacobite Syrian Christian Church. Motions by the church leaders and two Supreme Court decisions in the 20th century failed to heal the rift. In 1930, a reunion group split away and entered into communion with the Catholic Church as the Syro-Malankara Catholic Church, an Eastern Catholic Church with its own liturgy. | The word Malankara derives from the name of the island of Maliankara near Muziris, which according to tradition was the first place Thomas the Apostle landed in India. Initially the terms "Malankara Christians" or "Malankara Nasranis" were applied to all Saint Thomas Christians, but following the split the term was generally restricted to the faction loyal to Mar Thoma I, distinguishing them from the Catholic faction. Later, many of the churches that subsequently branched off have maintained the word in their names. At the time of the split, the branch affiliated with Mar Thoma was called the Puttankuttukar, or "New Party", while the branch that entered into Catholic obedience was designated the Pazhayakuttukar, or "Old Party". This latter group evolved into the Syro-Malabar Catholic Church. These appellations have been somewhat controversial, as both groups considered themselves the true heirs to the Saint Thomas tradition, and saw the other as heretical. Following the association with the Syriac Orthodox Church, the church was often known as the Malankara Syrian Church (Malayalam: മലങ്കര സുറിയാനി സഭ) in reference to their connection to the West Syrian tradition. As such they were often known as "Jacobites", "Syrian Jacobites", or "Jacobite Syrians", a reference to the Syriac Orthodox Church's connection to Jacob Baradaeus. After the split between Metropolitan- and the Patriarch-supporting factions, the Jacobite designation has been chiefly associated with the latter group, who emphasize their connection with Antioch. As a Saint Thomas Christian group, the Malankara Church traced its origins to Thomas the Apostle, said to have proselytized in India in the 1st century. Different strains of the tradition have him arriving either by sea or by land. There is no direct contemporary evidence for Thomas coming to India, but such a trip would certainly have been possible for a Roman Jew to have made; communities such as the Cochin Jews and the Bene Israel are known to have existed in India around that time. The earliest text connecting Thomas to India is the Acts of Thomas, written in Edessa perhaps in the 2nd century. Some early Indian sources, such as the "Thomas Parvam" or "Song of Thomas", further expand on the tradition of the apostle's arrival and activities in India and beyond. Generally he is described as arriving in the neighbourhood of Maliankara and establishing Seven Churches, the Ezharapallikal: Cranganore (ml:കൊടുങ്ങല്ലൂര്), Paravur (Kottakavu)(ml:കോട്ടക്കാവ്), Palayoor (ml:പാലൂർ ), Gokkamangalam (ml:ഗോക്കമംഗലം), Niranam (ml:നിരണം ), Chayal (ml:ചായൽ ) and Kollam (Quilon) (ml:കൊല്ലം ). Eusebius of Caesarea mentions that his mentor Pantaenus found a Christian community in India in the 2nd century, while references to Thomas' Indian mission appear in the works of 3rd- and 4th-century writers of the Roman Empire, including Ambrose of Milan, Gregory of Nazianzus, Jerome, and Ephrem the Syrian, showing that the Thomas tradition was well established across the Christian world by that time. Whatever the historicity of the Thomas tradition, the earliest organised Christian presence in India dates around the 3rd century, when East Syrian settlers and missionaries from Persia, members of what became the Church of the East or Nestorian Church, established themselves in Kerala. The Thomas Christians trace the further growth of their community to the mission of Thomas of Cana, a Nestorian from the Middle East said to have relocated to Kerala some time between the 4th and 8th century. The subgroup of the Saint Thomas Christians known as the Southists trace their lineage to the high-born Thomas of Cana, while the group known as the Northists claim descent from Thomas the Apostle's indigenous converts who intermarried with Thomas of Cana's children by his concubine or second wife. As the community grew and immigration by East Syrians increased, the connection with the Church of the East, centred in the Persian capital of Seleucia-Ctesiphon, strengthened. From the early 4th century the Patriarch of the Church of the East provided India with clergy, holy texts, and ecclesiastical infrastructure, and around 650 Patriarch Ishoyahb III solidified the Church of the East's jurisdiction over the Saint Thomas Christian community. In the 8th century Patriarch Timothy I organised the community as the Ecclesiastical Province of India, one of the church's illustrious Provinces of the Exterior. After this point the Province of India was headed by a metropolitan bishop, provided from Persia, the "Metropolitan-Bishop of the Seat of Saint Thomas and the Whole Christian Church of India". His metropolitan see was probably in Cranganore, or (perhaps nominally) in Mylapore, where the shrine of Thomas was located. Under him were a varying number of bishops, as well as a native Archdeacon, who had authority over the clergy and who wielded a great amount of secular power. The Rulers of Kerala, in appreciation for their assistance, gave to the Malankara Nazranis, three deeds on copper plates. They gave the Nasranis various rights and privileges which were written on copper plates. These are known as Cheppeds, Royal Grants, Sasanam etc. Five sheets of them are now in the possession of Mar Thoma Syrian Church headquarters at Thiruvalla. - Iravi Corttan Deed: In 1225 AD Sri Vira Raghava Chakravarti gave a deed to Iravi Corttan ( Eravi Karthan) of Mahadevarpattanam in 774. Two Brahmin families are witness to this deed showing that Brahmins were in Kerala by the 8th century. - Tharissa palli Deed I: Perumal Sthanu Ravi Gupta (844-885) gave a deed in 849 AD, to Isodatta Virai for Tharissa Palli (church) at Curakkeni Kollam. According to historians, this is the first deed in Kerala that gives the exact date. - Tharissa palli Deed II: Continuation of the above, given after 849 AD. These plates detail privileges awarded to the community by the then rulers. These influenced the development of the social structure in Kerala and privileges, rules for the communities . These are considered as one of the most important legal documents in the history of Kerala. The position of archdeacon – the highest for clergy who are not a bishop – had great importance in the church of India in the centuries leading up to the formation of an independent Malankara Church. Though technically subordinate to the metropolitan, the archdeacon wielded great ecclesiastical and secular power, to the extent that he was considered the secular leader of the community and served as effective head of the Indian Church in times when the province was absent a bishop. Unlike the metropolitan, who was evidently always an East Syrian sent by the patriarch, the archdeacon was a native Saint Thomas Christian. In the documented period the position was evidently hereditary, belonging to the Pakalomattam family, who claimed a privileged connection to Thomas the Apostle. Details on the archidiaconate prior to the arrival of the Portuguese are elusive, but Patriarch Timothy I (780 – 823) called the Archdeacon of India the "head of the faithful in India", implying an elevated status by at least that time. In the recorded period of its history, the office of archdeacon was substantially different in India than in the rest of the Church of the East or other Christian churches. In the broader Church of the East, each bishop was attended by an archdeacon, but in India, there was only ever one archdeacon, even when the province had multiple bishops serving it. Following the collapse of the Church of the East's hierarchy in most of Asia in the 14th century, India was effectively cut off from the church's heartland in Mesopotamia and formal contact was severed. By the late 15th century India had had no metropolitan for several generations, and the authority traditionally associated with him had been vested in the archdeacon. In 1491 the archdeacon sent envoys to the Patriarch of the Church of the East, as well as to the Coptic Pope of Alexandria and to the Syriac Orthodox Patriarch of Antioch, requesting a new bishop for India. The Patriarch of the Church of the East Shemʿon IV Basidi responded by consecrating two bishops, Thoma and Yuhanon, and dispatching them to India. These bishops helped rebuild the ecclesiastical infrastructure and reestablish fraternal ties with the patriarchate, but the years of separation had greatly affected the structure of the Indian church. Though receiving utmost respect, the metropolitan was treated as a guest in his own diocese; the Archdeacon was firmly established as the real power in the Malankara community. At the time the Portuguese arrived in India in 1498, the Saint Thomas Christians were in a difficult position. Though prosperous owing to their large stake in the spice trade and protected by a formidable militia, the tumultuous political climate of the time had placed the small community under pressure from the forces of the powerful rajas of Calicut, Cochin, and the various smaller kingdoms in the area. When the Portuguese under Vasco da Gama arrived on the South Indian coast, the leaders of the Saint Thomas community greeted them and proffered a formal alliance to their fellow Christians. The Portuguese, who had keen interest in implanting themselves in the spice trade and in expanding the domain of their bellicose form of Christianity, jumped at this opportunity. The Portuguese brought to India a particularly militant brand of Christianity, the product of several centuries of struggle during the Reconquista, which they hoped to spread across the world. Facilitating this objective was the Padroado Real, a series of treaties and decrees in which the Pope conferred upon the Portuguese government certain authority in ecclesiastical matters in the foreign territories they conquered. Upon reaching India the Portuguese quickly ensconced themselves in Goa and established a church hierarchy; soon they set themselves to bringing the native Christians under their dominion. Towards this goal, the colonial establishment felt it necessary to conduct the Saint Thomas Christians fully into the Latin Rite, both in bringing them into conformity with Latin church customs and in subjecting them to the authority of the Archbishop of Goa. Following the death of Metropolitan Mar Jacob in 1552, the Portuguese became more aggressive in their efforts to subjugate the Saint Thomas Christians. Protests on the part of the natives were frustrated by events back in the Church of the East's Mesopotamian heartland, which left them devoid of consistent leadership. In 1552, the year of Jacob's death, a schism in the Church of the East resulted in there being two rival patriarchates, one of which entered into communion with the Catholic Church, and the other of which remained independent. At different times both patriarchs sent bishops to India, but the Portuguese were consistently able to outmaneuver the newcomers or else convert them to Latin Rite Catholicism outright. In 1575 the Padroado declared that neither patriarch could appoint prelates to the community without Portuguese consent, thereby cutting the Thomas Christians off from their hierarchy. By 1599 the last Metropolitan, Abraham, had died, and the Archbishop of Goa, Aleixo de Menezes, had secured the submission of the young Archdeacon George, the highest remaining representative of the native church hierarchy. That year Menezes convened the Synod of Diamper, which instituted a number of structural and liturgical reforms to the Indian church. At the synod, the parishes were brought directly under the Archbishop's authority, certain "superstitious" customs were anathematized, and the indigenous liturgy, the Malabar Rite, was purged of elements unacceptable by the Latin standards. Though the Saint Thomas Christians were now formally part of the Catholic Church, the conduct of the Portuguese over the next decades fueled resentment in parts of the community, ultimately leading to open resistance. Over the next several decades, tensions seethed between the Latin prelates and what remained of the native hierarchy. This came to a head in 1641 with the ascension of two new protagonists on either side of the contention: Francis Garcia, the new Archbishop of Kodungalloor, and Archdeacon Thomas, the nephew and successor to Archdeacon George. In 1652, the escalating situation was further complicated by the arrival in India of a mysterious figure named Ahatallah. Ahatallah arrived in Mylapore in 1652, claiming to be the rightful Patriarch of Antioch who had been sent by the Catholic pope to serve as "Patriarch of the Whole of India and of China". Ahatallah's true biography is obscure, but some details have been established. He appears to have been a Syriac Orthodox Bishop of Damascus who converted to Catholicism and went to Rome in 1632. He then returned to Syria in order to bring the Syriac Orthodox Patriarch Ignatius Hidayat Allah into communion with Rome. He had not accomplished this by the time Hidayat Allah died in 1639, after which point Ahatallah began claiming he was Hidayat Allah's rightful successor. In 1646 he was in Egypt at the court of the Coptic Pope Mark VI, who dispatched him to India in 1652, evidently in response to a request for aid from Archdeacon Thomas. Reckoning him an impostor, the Portuguese arrested him, but allowed him to meet with members of the Saint Thomas Christian clergy, whom he impressed greatly. The Portuguese put him on a ship bound for Cochin and Goa, and Archdeacon Thomas led his militia to Cochin demanding to meet with the Patriarch. The Portuguese refused, asserting that he was a dangerous invader and that the ship had already sailed on to Goa. Ahatallah was never heard from again in India, and rumours soon spread that Archbishop Garcia had disposed of him before he ever reached Goa. Contemporary accounts allege that he was drowned in Cochin harbour, or even that the Portuguese burned him at the stake. In reality, it appears that Ahatallah did in fact reach Goa, from whence he was sent on to Europe, but he evidently died in Paris before reaching Rome where his case was to be heard. In any event, Garcia's dismissiveness towards the Saint Thomas Christians' appeals only embittered the community further. This was the last straw for the Saint Thomas Christians, and in 1653 Thomas and representatives of the community met at the Church of Our Lady in Mattancherry to take bold action. In a great ceremony before a crucifix and lighted candles, they swore a solemn oath that they would never obey Garcia or the Portuguese again, and that they accepted only the Archdeacon as their shepherd. The Malankara Church and all its successor churches regard this declaration, known as the Coonan Cross Oath (Malayalam: കൂനൻ കുരിശു സത്യം), after the outdoor cross in the churchyard, as the moment when their church regained its independence. The oppressive rule of the Portuguese padroado provoked a violent reaction on the part of the indigenous Christian community. The first solemn protest took place in 1653, known as the Coonan Kurishu Satyam (Coonan Cross Oath). Under the leadership of Archdeacon Thoma, the St. Thomas Christians publicly took an oath in Mattancherry, Cochin, that they would not obey the Portuguese Catholic bishops and the Jesuit missionaries. Until the Portuguese arrival, Malankara Christians never even heard of the Roman Catholic Pope.Unfortunately there was no Metropolitan present in the Malankara Church at that time. Hence in the same year, at Alangad, Archdeacon Thoma was ordained, by the laying on of hands of twelve priests, as the first known indigenous Metropolitan of Kerala, under the name Mar Thoma I. The Portuguese missionaries attempted for reconciliation with Saint Thomas Christians but was not successful. Later Pope Alexander VII sent the Syrian bishop Joseph Sebastiani at the head of a Carmelite delegation who succeeded in convincing majority of Saint Thomas Christians, including Palliveettil Chandy Kathanar and Kadavil Chandy Kathanar that the consecration of Archdeacon as Metropolitan was not legitimate as per the traditional apostolic standards. Later Palliveettil Chandy Kathanar was consecrated as the bishop for the Syrian Catholics with the historic title 'The Metropolitan and the Gate of all India' which denotes a Quasi Patriarchal status with all India jurisdiction. This led to the first permanent split in the Saint Thomas Christian community. Thereafter, the faction affiliated with the Catholic Church under Parambil Mar Chandy was designated the Pazhayakoottukar, or "Old Party", while the branch affiliated with Mar Thoma was called the Puthankoottukar, or "New Party". These appellations have been somewhat controversial, as both groups considered themselves the true heirs to the Saint Thomas tradition, and saw the other as heretical. After the Coonan Cross Oath, between 1661 and 1662, out of the 116 churches, the Catholics claimed eighty-four churches, and the Archdeacon Mar Thoma I with thirty-two churches. The eighty-four churches and their congregations were the body from which the Syro Malabar Catholic Church and Chaldean Syrian Church have descended. The other thirty-two churches and their congregations were the body from which the Malankara Syrian Churches (Jacobite Syrian Christian Church, Malankara Orthodox Syrian Church, Malabar Independent Syrian Church, Malankara MarThoma Syrian Church and Syro-Malankara Catholic Church originated. The Catholic faction constantly challenged the legitimacy of the consecration of Archdeacon as Metropolitan .This made it essential to rectify the illegetimacy of the consecration of Archdeacon as Metropolitan. In 1665, Mar Gregorios Abdul Jaleel, a Bishop sent by the Syriac Orthodox Patriarch of Antioch arrived in India and the Saint Thomas Christians under the leadership of the Archdeacon welcomed him. Gregorios Abdal Jaleel regularised the consecration of Archdeacon as Metropolitan as per the apostolic standards of Kaiveppu(Traditional legitimate way of laying hands by a valid Bishop). This resulted in the spiritual authority of the Antiochean Patriarchate and the reaffirmation of the orthodox faith in the Church. The 18th century saw the gradual introduction of West Syrian liturgy and script to the Malabar Coast, a process that continued through the 19th century. The arrival of Mar Gregorios in 1665, marked the introduction of Oriental Orthodoxy in the Malankara Church. The Malankara Church experienced a series of splits over the centuries, resulting in the formation of several churches, some of which embraced the jurisdiction of foreign churches, while others remained autocephalous and autonomous churches. The churches that share the Malankara Church tradition are: - Jacobite Syrian Christian Church: an autonomous oriental orthodox church under the jurisdiction of the Syriac Orthodox Patriarch of Antioch. - Malankara Orthodox Syrian Church: an autonomous and autocephalous oriental orthodox church under the jurisdiction of the autocephalous Catholicos of the East. - Malabar Independent Syrian Church: an autonomous and autocephalous church under the jurisdiction of its own independent Metropolitan. - Mar Thoma Syrian Church: an autonomous Oriental Syrian church under the jurisdiction of Marthoma Metropolitan. - Syro-Malankara Catholic Church: a self-governing Eastern Catholic church within the Catholic communion.

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Historically, armed conflict has thrown a spotlight on the aggressive spread of deadly infectious diseases, which are easily transmitted when large numbers of people are displaced. But war has also had a lesser known, and more positive effect on dentistry. In 1914, Britain had no official dental branch of the armed services, and so dentists who were keen to serve their fellow countrymen enlisted as combatants. The U.S. experienced similar problems. When it entered the war, the U.S. Army had just 86 officers on its dental staff to treat about 200,000 troops. As the number of enlisted men swelled, so too did the dental staff. Naturally, dentists who served their country in the war treated soldiers for routine dental problems, like toothaches and fractured teeth, as well as more severe trauma caused by the conflict itself. For many of the enlisted men, the dental care they received in the Army was the first they’d ever had. At University Associates in Dentistry, we pride ourselves on offering the latest dental technologies and treatments to our valued patients. Call (312) 704-5511 to request an appointment for preventive care, cosmetic dentistry, or dental implants in Chicago. Physicians and dentists alike agree that it’s critical to get sleep apnea under control. Sleep deprivation can increase your risk of serious medical complications, some of which may be life-threatening. You can hear more about them when you watch this informative video, presented by a professor of neuroscience. This professor explains that sleep deprivation inhibits your brain’s ability to form new memories, and it increases the levels of a toxic protein called beta amyloid. Beta amyloid in the brain is associated with Alzheimer’s disease. Furthermore, failure to seek sleep apnea treatment may increase the risk of cancer and cardiovascular disease. University Associates in Dentistry is your source for effective, non-CPAP sleep apnea treatment in Chicago. Call us today at (312) 704-5511, and ask us how our dentists can treat your sleep apnea. Modern dental implants are comprised of titanium. The discovery that titanium is able to fuse with natural bone was made by accident in 1952. Since that time, dentists have continued to refine the materials and technique used to restore patients’ smiles. Although modern dental implants are an impressive innovation, implants have ancient roots. Throughout history, humans have used some strange materials to replace missing teeth. In recent years, bamboo has been prized by homeowners as a sustainable, eco-friendly flooring material. That’s because bamboo can be harvested after just a few years of growth. The rapid growth rate of bamboo is perhaps one reason why the ancient Chinese decided it would make a good replacement for teeth. About 4,000 years ago, Chinese dentists carved the hard, durable bamboo into a tooth-shaped implant and then tapped it into the unfortunate patient’s jawbone. Ancient Egyptians relied on oxen. When they slaughtered an ox, they used every part of the animal possible. The hides were used to make furniture and the bones were used to make dental implants for missing teeth. The Egyptians held the oxen bone implants in place with gold wire. It’s unknown if the implants were placed before death or after it. It’s conceivable that the implants were placed after death, since great care was taken to prepare the bodies of the deceased for the afterlife. In the 1930s, archaeologists were excavating an ancient Mayan site in Honduras when they discovered part of a human mandible. The jawbone was dated to about 600 CE, and is believed to be from a woman who died in her twenties. The jawbone had three dental implants made from tooth-shaped pieces of shells. Decades later, a researcher took radiographs of the mandible. He discovered that, based on the bone formation around the shells, these implants had been placed while the woman was still alive. University Associates in Dentistry is known as leading experts in dental implants in the Chicago area. Our dentists specialize in same-day dental implants, which lets you walk away with a complete, beautiful smile in just one appointment. If you have missing teeth, call us today at (312) 704-5511. You already know that it’s important to see a dentist every six months to reduce your risk of cavities and other oral health problems. But did you know that your teeth and gums can also affect your waistline, and vice versa? There are a few ways in which oral health and weight loss intersect. Individuals who are overweight have a higher risk of periodontal disease. If you’re looking for motivation to stick with your New Year’s resolution to lose weight, consider a recent study published in the medical journal Oral Diseases. It indicates that individuals who are overweight or obese have a nearly six-fold increased risk of suffering from periodontal disease. It’s thought that the increased presence of systemic inflammation in overweight individuals may play a role in the elevated risk of gum disease. This wasn’t the only study to evaluate this issue. Researchers from the Case Western Reserve University School of Dental Medicine conducted a study that led them to conclude that overweight individuals who successfully lose weight are better able to fight off gum disease. Poor oral health can lead to poor nutrition. A person’s waistline can influence his or her oral health, but the reverse is also true. People who have poor oral health are more likely to have poor nutrition, which can negatively affect weight management. For example, if you have severe toothaches, loose teeth, or missing teeth, you might think twice before reaching for healthy foods like crunchy apples, carrots, and almonds. You might prefer softer foods that are easier to eat, like sugar-laden muffins that can add to your waistline. Oral health and weight management benefit from the same lifestyle choices. Although it can be disheartening to learn about the ways oral health and weight management can be negatively affected, there is good news. The same healthy habits that benefit your waistline will also support your oral health. For example, if you’re trying to lose weight by cutting out soda, you’ll also have a lower risk of tooth decay. Another trick is to brush your teeth immediately after a meal so you won’t be tempted to keep snacking. The entire team at University Associates in Dentistry is committed to helping you improve your oral health and overall wellness. New and current general dentistry patients in Chicago can give us a call at (312) 704-5511 to request a dental consultation. We always welcome your questions and concerns about your oral care routine. - Dental History - Gum Disease - Dental Implants - Dental Health - Teeth Whitening - Sleep Apnea - Bad Breath - Dental Veneers - Sports Dentistry - Dental Bridges - Dental Crowns - Tooth Loss - CT Scans - DEXIS CariVu

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Did you know? 1 in 4 girls and 1 in 6 boys will experience some form of sexual abuse by age 18.* Disclosing abuse takes bravery. If a child has trusted you with a disclosure of abuse, it is imperative that you act on the child's behalf. Together, we can help begin the healing. Statistics prove that 90% of alleged offenders are a person the child or family knows and often trusts, but only 1 in 10 children will ever disclose this violation of their innocence. When it comes to abuse, prevention isn't only possible, it is pivotal to the health and safety of our community. Learn what you can do to help stop the cycle of abuse. In 2018, Children's Home Child Advocacy Center provided forensic interviews and advocacy for 350 children and their families. Help us help others.

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|Saint Isaac's Cathedral| |Affiliation||State Russian Museum| |Location||Saint Isaac's Square 4, | |Architect(s)||Auguste de Montferrand| |Style||Late Neoclassical, Byzantine and Greek (cross church)| 260,000 m3 (volume) |Length||104.5 m (interior)| 111.3 m (stairs) |Width||91 m (interior)| 97.6 m (stairs) |Interior area||7,000 m2 (interior) | 8,000 m2 (stairs) |Height (max)||101.52 m (top cross)| 31.5 m (nave interior) 80 m (dom ceiling) |Dome dia. (outer)||25.8 m| Saint Isaac's Cathedral or Isaakievskiy Sobor (Russian: Исаа́киевский Собо́р) is a cathedral that currently functions as a museum in Saint Petersburg, Russia. It is dedicated to Saint Isaac of Dalmatia, a patron saint of Peter the Great, who had been born on the feast day of that saint. It was originally built as a cathedral but was turned into a museum by the Soviet government in 1931 and has remained a museum ever since. In 2017, the Governor of Saint Petersburg offered to transfer the cathedral back to the Russian Orthodox Church, but this was not accomplished due to the protests of St Petersburg citizens opposing the offer. The church on St Isaac's Square was ordered by Tsar Alexander I, to replace an earlier structure by Vincenzo Brenna, and was the fourth consecutive church standing at this place. A specially appointed commission examined several designs, including that of the French-born architect Auguste de Montferrand (1786–1858), who had studied in the atelier of Napoleon's designer, Charles Percier. Montferrand's design was criticised by some members of the commission for the dry and allegedly boring rhythm of its four identical pedimented octastyle porticos. It was also suggested that despite gigantic dimensions, the edifice would look squat and not very impressive. The members of the commission, which consisted of well-known Russian architects, were also particularly concerned by necessity to build a new huge building on the old unsecure foundation. The emperor, who favoured the ponderous Empire style of architecture, had to step in and solve the dispute in Montferrand's favour. The cathedral took 40 years to construct, under Montferrand's direction, from 1818 to 1858. The building of the cathedral took so long, that it left an idiom to Finnish language: rakentaa kuin Iisakinkirkkoa (To build like the church of Isaac) when speaking of long-term construction projects. To secure the construction, the cathedral's foundation was strengthened by driving 25,000 piles into the fenland of Saint Petersburg. Innovative methods were created to erect the giant columns of the portico. The construction costs of the cathedral totalled an incredible sum of 1 000 000 gold rubles. Under the Soviet government, the building was stripped of religious trappings. In 1931, it was turned into the Museum of the History of Religion and Atheism, the dove sculpture was removed, and replaced by a Foucault pendulum. On April 12, 1931, the first public demonstration of the Foucault pendulum was held to visualize Copernicus’s theory. In 1937, the museum was transformed into the museum of the cathedral, and former collections were transferred to the Museum of the History of Religion (located in the Kazan Cathedral). During World War II, the dome was painted over in gray to avoid attracting attention from enemy aircraft. On its top, in the skylight, a geodesical intersection point was placed, to determine the positions of German artillery batteries. With the fall of communism, the museum was removed and regular worship activity has resumed in the cathedral, but only in the left-hand side chapel. The main body of the cathedral is used for services on feast days only. On January 10, 2017 Georgy Poltavchenko, the Governor of St. Petersburg, announced that the cathedral would be transferred to the Russian Orthodox Church . The key protocols of the transfer were defined by the order issued by St. Petersburg’s Committee on Property Relations on December 30, 2016. The document expired on December 30, 2018. The new order can be issued upon request from the Russian Orthodox Church, but no such request has yet been submitted.. The transfer of Saint Isaac's Cathedral in use the ROC agreed in January 2017, but the decision has caused discontent of the townspeople, who defended the status of the museum. The decision of the city authorities was disputed in the courts. Currently, the status of the building is museum. Today, church services are held here only ecclesiastical occasions. The neoclassical exterior expresses the traditional Russian-Byzantine formula of a Greek-cross ground plan with a large central dome and four subsidiary domes. It is similar to Andrea Palladio's Villa La Rotonda, with a full dome on a high drum substituted for the Villa's low central saucer dome. The design of the cathedral in general and the dome in particular later influenced the design of the United States Capitol dome, Wisconsin State Capitol in Madison, Wisconsin, and the Lutheran Cathedral in Helsinki. The exterior is faced with gray and pink stone, and features a total of 112 red granite columns with Corinthian capitals, each hewn and erected as a single block: 48 at ground level, 24 on the rotunda of the uppermost dome, 8 on each of four side domes, and 2 framing each of four windows. The rotunda is encircled by a walkway accessible to tourists. 24 statues stand on the roof, and another 24 on top of the rotunda. The cathedral's main dome rises 101.5 metres (333 ft); its exterior is gilded. The dome is decorated with twelve statues of angels by Josef Hermann. These angels were likely the first large sculptures produced by the then novel process of electrotyping, which was an alternative to traditional bronze casting of sculptures. Montferrand's design of the dome is based on a supporting cast iron structure. It was the third historical instance of cast iron cupola after the Leaning Tower of Nevyansk (1732) and Mainz Cathedral (1826). The cathedral's bronze doors, covered in reliefs by Ivan Vitali, are patterned after the celebrated doors of the Battistero di San Giovanni in Florence, designed by Lorenzo Ghiberti. Suspended underneath the peak of the dome is a sculpted white dove representing the Holy Spirit. Internal features such as columns, pilasters, floor, and statue of Montferrand are composed of multicolored granites and marbles gathered from all parts of Russia. The iconostasis is framed by eight columns of semiprecious stone: six of malachite and two smaller ones of lazurite. The four pediments are also richly sculpted. The interior was originally decorated with scores of paintings by Karl Bryullov and other great Russian masters of the day. When these paintings began to deteriorate due to the cold, damp conditions inside the cathedral, Montferrand ordered them to be painstakingly reproduced as mosaics, a technique introduced in Russia by Mikhail Lomonosov. This work was never completed. William Handyside and other engineers used a number of technological innovations in the construction of the building. The portico columns were raised with the use of large wooden frameworks before the walls were erected. The building rests on 10,000 tree trunks that were sunk by a large number of workers into the marshy banks upon which the cathedral is situated. The dome was gilded by a technique similar to spraypainting; the solution used included toxic mercury, the vapors of which caused the deaths of sixty workers. The dozen gilded statues of angels, each six metres tall, facing each other across the interior of the rotunda, were constructed using galvanoplastic technology, making them only millimeters thick and very lightweight. St. Isaac's Cathedral represents the first use of this technique in architecture. The meticulous and painstakingly detailed work on constructing the St. Isaac's Cathedral took 40 years to complete. This extended construction left an expression in the Finnish language, rakentaa kuin Iisakin kirkkoa ("to build like St. Isaac's Church"), for lengthy and never-ending megaprojects. The first St. Isaac's Church (Lithography of Auguste de Montferrand's drawing, 1710) Floorplan of St. Isaac's Cathedral St. Isaac blessing the Emperor Theodosius and his wife Flaccilla Interior of the cathedral View a 360 Panorama here View of the main iconostasis, showing the malachite and lapis lazuli columns Iconostasis of one of the side chapels Interior of the great dome, honoring the Holy Spirit Twelve great gilt angels, taking the part of the caryatides, support consoles on which stand the bases of the pilasters which form the interior row of the dome and separate the windows. They are twenty-one feet high, and were made by the galvanoplastic process in four pieces, whose welding together is invisible. They could in this manner be made so light that, in spite of their dimensions, they would not be too heavy for the cupola. This crown of gilt angels, poised amid a flood of light, and shining with rich reflections, produces an extremely rich effect. |Wikimedia Commons has media related to Saint Isaac's Cathedral.|

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Leda Atomica is a painting by Salvador Dalí, made in 1949. The picture depicts Leda, the mythological queen of Sparta, with the swan. Leda is a frontal portrait of Dalí’s wife, Gala, who is seated on a pedestal with a swan suspended behind and to her left. Different objects such as a book, a set square, two stepping stools and an egg float around the main figure. In the background on both sides, the rocks of Cap Norfeu (on the Costa Brava in Catalonia, between Roses and Cadaqués) define the location of the image. After the atomic bomb was dropped on Hiroshima, Dalí took his work in a new direction based on the principle that the modern age had to be assimilated into art if art was to be truly contemporary. Dalí acknowledged the discontinuity of matter, incorporating a mysterious sense of levitation into his Leda Atomica. Just as one finds that at the atomic level particles do not physically touch, so here Dalí suspends even the water above the shore—an element that would figure into many other later works. Every object in the painting is carefully painted to be motionless in space, even though nothing in the painting is connected. Leda looks as if she is trying to touch the back of the swan’s head, but doesn’t do it. Dalí shows us the hierarchized libidinous emotion, suspended and as though hanging in midair, in accordance with the modern ‘nothing touches’ theory of intra-atomic physics. Leda does not touch the swan; Leda does not touch the pedestal; the pedestal does not touch the base; the base does not touch the sea; the sea does not touch the shore. . . .” Leda Atomica is organized according to a rigid mathematical framework, following the “divine proportion”. Leda and the swan are set in a pentagon inside which has been inserted a five-point star of which Dalí made several sketches. The five points of the star symbolize the seeds of perfection: love, order, light (truth) willpower and word (action). The harmony of the framework was calculated by the artist following the recommendations of Romanian mathematician Matila Ghyka. In reference to the classical myth Dalí identified himself with the immortal Pollux while his deceased older brother (also called Salvador) would represent Castor, the mortal of the twins. Another equivalence could be made regarding the other twins of the myth, Dalí’s sister Ana María being the mortal Clytemnestra, while Gala would represent divine Helen. Salvador Dalí himself wrote: «I started to paint Leda Atómica which exalts Gala, the metaphysical goddess and succeeded to create the “suspended space”». Dalí’s Catholicism enables also other interpretations of the painting. The painting can be conceived as Dalí’s way of interpreting the Annunciation. The swan seems to whisper her future in her ear, possibly a reference to the legend that the conception of Jesus was achieved by the introduction of the breath of the Holy Ghost into the Virgin Mary’s ear. Leda looks straight into the bird’s eyes with an understanding expression of what is happening to her and what will happen in the future to her and to her unsure reality. Dalí’s transformation of Mary is the result of love as if he created his love to Gala, like God to Mary

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The Baby Boomer generation covers individuals born from around 1948 to 1959. Many of the individuals in this age range are quickly approaching retirement after decades of work. Unfortunately, there are major concerns about this shift to retirement, as some people feel that their generation wasn’t taught how to handle personal finances. This claim may seem bold on the surface, but let’s go over the statistics behind it, and focus on how: - Baby Boomers Can Increase Their Knowledge of Personal Finances - Younger Generations Can Plan to Handle Their Financial Needs Personal Finance Knowledge and the Baby Boomers So, what weren’t the Baby Boomers taught about personal finance? Many people first consider the stock market when trying to answer that question. After all, the stock market has changed a lot over the last few decades, and a lot of the rules about how if functioned were easy to miss. While it is true that the tricks to managing stocks and bonds – along with keeping a diversified portfolio – were not taught to many in the Baby Boomer generation, there are other financial concerns involving: Many in the Baby Boomer generation – around 70 million people – have simply not saved for retirement. In fact, one study in 2014 reported that around 33% of Baby Boomers had saved nothing for their retirement. Baby Boomers who have saved for retirement have usually put away insufficient funds. Median retirement savings for the group hovered at $200,000. While this looks like a large number, many experts say you will need around $1 million to reach the end of your retirement. High Amounts of Debt Baby Boomers are also carrying significantly more debt than older generations. Studies have determined that – on average – Baby Boomers are carrying more than $100,000 in debt. Many members of this generation are still carrying a mortgage after they reach 65. Handling Personal Finances Now So, if some Baby Boomers did not get the financial education they needed when they were younger, what does that mean? High levels of debt and poor retirement savings can force individuals to continue working for longer. A lack of retirement savings and the burden of debt can also force retirees to fall back on their family members or social services. This could create a strain in some areas of the country, especially where the population of Baby Boomers continues to increase. States like South Carolina, Florida, and Arizona could all be impacted. Some of the younger members of the Baby Boomer generation still have time to increase their retirement savings. Anyone can take steps to handle high levels of debt. Some options for getting rid of debt can include: - Refinancing a Mortgage - Consolidating Credit Card Debt - Paying Off Debt with a Lump Sum Payment Getting the funds for a lump sum payment may not be as impossible as it sounds. Some individuals may be able to take out a low-interest personal loan from their bank or credit union. Individuals in many states, for example in the south can also get immediate funds with a title loan in South Carolina. Learn More About Your Personal Finances Today The Baby Boomer generation is not the only cohort in the U.S. that could benefit from learning more about personal finances. Millennials – along with members of Gen Z and Gen X – could all gain financial security by learning about: - The Best Steps for Retirement Saving - Real Estate Investing - Tips for Handing the Stock Market Keeping your debt low and your savings high can ensure that you are ready when you retire, no matter what generational group you belong to. Focusing on eliminating your debt and setting up a retirement account today is a great way to start handling your personal finances.

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