The Australian government has announced a major program of reform with the move to primary maternity care, a program of change that appears to be at odds with current general public perceptions regarding how maternity care is delivered.A critical discourse analysis of articles published in 'The Age', a newspaper with national distribution, subsequent to the release of the discussion paper by the Australian Government in 2008 was undertaken. The purpose was to identify how Australian maternity services are portrayed and what purpose is served by this representation to the general public.Findings from this critical discourse analysis revealed that Australian maternity services are being portrayed to the general public as an inflexible outdated service struggling to meets the needs of pregnant women and in desperate need of reform. The style of reporting employed in this newspaper involved presenting to the reader the range of expert opinion relevant to each topic, frequently involving polarised positions of the experts on the issue.The general public are presented with a conflict, caught between the need for changes that come with the primary maternity model of care and fear that these change will undermine safe standards. The discourse; 'Australia is one of the safest countries in which to give birth or be born, what is must be best', represents the situation where despite major deficiencies in the system the general public may be too fearful of the consequences to consider a move away from reliance on traditional medical-led maternity care. The Australian government has announced a major program of reform with the move to primary maternity care in line with the recommendations of the national review of maternity services released in 2009. The reform represents a program of change that appears to be at odds with current general public perceptions regarding how maternity care is delivered. Primary maternity services offer women continuity of primary carer with a midwife or general practitioner, reserving obstetric services for only those in clinical need ,2. AustrAlthough many women expect childbirth to be a potentially non-affirming event steeped in pain and fear , giving Many women know little about maternity care prior to becoming pregnant for the first time and are guided by the advice of health professionals, family and friends or the media when choosing the maternity care that best suits their needs. Information presented in the media can be highly persuasive as illustrated by two recent high profile exposès on maternity care including the US based DVD 'the business of being born'  and the Implementation of the primary maternity care reforms represents a major change to the way maternity care has been traditionally delivered in Australia. Successful implementation requires the support of the general public for whom the service is intended. One source of influence on general public opinion is the newspaper media and the news feeds that spin off to television and radio from feature articles of interest. The powerful use of language in a headline is used to attract general public attention to reports on controversial topics affecting Australian maternity care. This study examines the newspaper articles published in 'The Age' newspaper subsequent to the release of the Government discussion paper 'improving maternity services in Australia' in 2008  that herA critical discourse analysis of articles published in the 'The Age' subsequent to the release of the discussion paper by the Australian Government in 2008  was undeCritical analysis of discourse as a methodology was chosen for this study because language takes on greater significance in the arena of providing and consuming services . ObstetrCritical social theory has greatly influenced the development of CDA bringing together a wide variety of critical social theories including the way power is conceptualized . ThroughAll research data consisted of articles featuring the topics of maternity services or childbirth published in 'The Age' newspaper. Articles were obtained from the public domain, accessed through an online search of 'The Age' newspaper website. Personal information was not retrieved from any source and there was no participant involvement.A search was conducted on 'The Age' newspaper website for articles including the search terms; maternity services, birth and childbirth. A total of thirty-eight articles were indentified and included in the study. The title of each article including date and section of publication is supplied in Table Fairclough's approach to CDA links textual and sociological analysis in a way that foregrounds issues of power, resistance and identity . In thisAnalysis undertaken at the socio-cultural level refers to an analysis of the social context in which the text under investigation is produced. Texts were analysed for each key stakeholder group presented in the news article to uncover the unspoken and unstated assumptions implicit within them which have shaped the very form of the text in the first place . This leAnalysis undertaken at the level of discourse practice is concerned with the production, distribution and consumption of the text . In thisAnalysis at the textual level is concerned with the minutiae of the text such as how it is formed and what particular vocabulary and style is used in order to produce meaning . This stCritical discourse analysis is an interpretive process and acknowledges the multiple interpretations that can emerge from the text. The source of text included in the study has been explained and matched to the aims of the research. Sufficient quantities of text have been included in the analysis to capture all that can be known or said on the topic. Rigour in this study was enhanced through careful selection of text ensuring the discourses of all key stakeholders were represented in the analysis, as illustrated in Table Critical analysis of articles published in 'The Age' generated a number of discourses exerting influence on general public opinion. By far the majority of articles were concerned with sensationalising the deficiencies of maternity services. The articles featured attention grabbing headings, highlighting issues pertaining to the state of maternity services, supplemented by a range of expert opinions including the relevant government authority, medical or obstetric experts, Australian College of Midwives (ACM) and consumer groups.Expert consumer opinion was sought by 'The Age' from organisations such as maternity coalition or future families, advocates for primary maternity care reform supporting natural birth options. These organisations are well organised publicity machines promoting their position on natural childbirth . What waIn the process of sensationalising the deficiencies of maternity services, a number of articles extensively reported on the findings of a survey of 2792 mothers highlighting the traumatic or unsatisfactory experiences of women giving birth. Discourses generated from a critical analysis of that study included; 'the interests of women and their babies must be the focus of maternity care, not the system and those who work in it', 'next please, feeling depersonalised in the queue'. These discourses imply that current maternity services operate in the interests of the institution and maternity care professions and not in the interests of the women receiving care. The woman's personal experience and special needs are dismissed in an overstretched system providing a 'one size fits all service'. Selected statements illustrating the meanings of these discourses included:'Women feeling like cattle being pushed through herding yards that put both their own and their babies' lives at risk. Hundreds of women felt that both public and private maternity wards are overcrowded, needed more midwives, performed too many unnecessary medical interventions and did not provide enough non-drug options for pain relief (quote article 18).'Nothing could have prepared me for my horrible birth experience - "herding yards does not go nearly far enough in describing the way the hospital treats new mothers and babies (quote article 14).The safety of overcrowded and understaffed metropolitan maternity services is called into question in the majority of these news articles. It has been argued that maternity care in Australia is delivered in an outmoded 'hospital nursing' model  that has'A large public hospital means a huge variation in staff on different shifts, which leads to inconsistent care and the danger of falling through the cracks' (quote article 17).'The most concerning theme centres on the apparent shortage of resources in public hospitals, leaving many women feeling as if they and their infants are being exposed to unacceptable risk' (quote articles 18 & 21).'Because of workforce difficulties, care is fragmented. Women might see 12 or 13 diffent people during the pregnancy' (quote article 27).A number of the newspaper articles reported on the findings of the national review of maternity services released in 2009. One of the main messages highlighted in the articles is the need to respect women's right to choose, inferring that women are not being offered choice in the maternity care they receive. Some women in an attempt to investigate childbirth options find themselves labelled by the health professionals, on whom they rely, as being 'difficult' or 'untrusting' . Discour'Stop treating pregnancy as an illness and respect women's birth choices' (quote article 35).'Women seduced by the "empowering" idea that only a woman knows how to deliver her child forget that 100 years ago 1 in 10 women died from complications of childbirth and 1 in 10' (quote article 25).'Women do not have to prove to health professionals that their healthcare choices are good or worthy ones to have the right to decide' (quote article 1).Several newspaper articles question why Australian women are more anxious about their pregnancies despite Australia's safe record in childbirth. The chance of a women dying during childbirth in Australia is remote . Of conc'Many women are feeling more, rather than less, anxious about the birth process. Some blame this on our risk-averse society, saying the screens and tests and the increasing level of intervention in birth and pregnancy is geared towards making women fearful. Antenatal care has become antenatal scare' (quote article 7).'The woman's surgery was scheduled without her consent and she claimed she was bullied by hospital staff, who said her baby could die if she did not follow their advice. This new mother never wanted to birth at home - she wanted the support of the hospital but the system would not provide the care' (quote article 30).'In one Australian study, 62% of women who had a caesarean section in a private hospital said their health care provider had recommended it' (quote article 1).'There should be more continuity of care. Knowing your carer and trusting your carer removes the fear from childbirth and fear leads to more interventions' (quote article 19).The plight of rural maternity services was highlighted in a number of articles as a serious deficiency in current maternity service delivery , a situa'Since 1996, 40 maternity units had closed across the state and others were near closure. It's reflective of a general shortage of GP's across rural Australia. As a society we have not invested enough in GP proceduralists: doctors who provide obstetric care, anaesthetics or emergency' (quote article 26).'Urgent action is required to prevent women enduring "roadside births" as they travel hundreds of kilometres to dwindling maternity services in regional and rural Australia' (quote article 34).'Reopen my local maternity unit. Travelling while in labour is not only uncomfortable, but dangerous. .All articles retrieved for this study presented a range of expert opinion on the topic featured, usually including the relevant government authority, medical or obstetric experts, the ACM and consumer groups. Opinions represented a range of views often involving polarised positions on the issue. Consumers and midwives reinforced the position of natural birth and challenged increasing rates of medical intervention. Medicine or obstetrics highlighted the dangers of medically unassisted childbirth while the government defended the proposed maternity service policy direction. The main issue debated in the articles centred on contention surrounding government support for midwifery -led maternity services extending to including controversial home birth trials. As exemplified in the statement:'Victorian women will be able to give birth at home - with hospital back up for the first time - under a pilot project starting at three hospitals next year' (quote article 22).The safety record of home birth is reported in a number of newspaper articles as having received a boost with several large studies in recent years reporting no significant difference between planned hospital birth and planned home births, as long as the mothers have access to trained midwives ,35.'A Dutch study of more than 500,000 women reported that planning a home birth does not increase the risks of perinatal mortality and severe perinatal morbidity among low risk women provided they were supported by well trained midwives and a good transportation and referral system' (quote article 24).Medical or obstetric opinion reported in the newspaper articles reflect the position that they are the guardians of safety in childbirth in the belief that only they have the training and expertise for safe birth outcomes to be achieved . The exp'Of course, women might feel that sometimes the medical profession interferes too much in what is a natural process, but the reality is that if left to mother nature then the outcomes is not very good often. There needs to be a sensible balance struck between interfering in a natural process but judiciously intervening when things start to go wrong, or preferable before things start to go wrong' (quote article 7).'The trouble is we take safety for granted now and are arguing about quality issues, like maternal satisfaction, which is important. But I'm sorry not as, as a clinician, survival is the most important thing' (quote article 25).'If birth is a natural process so is getting cancer and dying' (quote article 12).'It's a myth to say that the most important thing is a healthy baby. Traumatic birth gets carried with you - you don't leave it at the hospital- and it can have the most profound consequences for both the mother and baby' (quote article 7).On the issue of expanding midwifery -led maternity services as part of the proposed primary maternity care reform agenda some medical and obstetric opinion reported in new articles became divergent as seen in the following statements:'I fear the introduction of a system where women are pressured into having a natural birth that puts them and their baby at risk' (quote article 18).'If we can have a patient seeing either the midwife or the GP depending on who is the appropriate person at the time, then that's going to benefit the patients and free the GP's up to be able to see other people. The GP's in rural area's providing birthing services know they can't do it by themselves' (quote article 23.1)On the issue of planned home birth there is strong resistance reported in news articles from medical experts a position supported in a recently published systematic review of the medical literature on the maternal and newborn safety . Finding'Any birth at home under the care of midwives was unsafe and should not be supported by governments (quote article 2).A source of confusion for the general public is evident in reports of obstetric opinion where midwifery services are only recognised as they relate to home birth, failing to acknowledge the work of midwives across the full range of maternity services. Discourse generated in this study; 'midwives act irresponsibly when attending a women birthing at home', 'home birth is a return to times past where mothers and babies died in vast numbers'. Selected statements illustrating the meanings of these discourses included:'Midwives do things in a home setting, that no maternity service around the developed world would think a good idea' (quote article 36).'Home births with or without midwife help, increase the risk of infant death three fold' (quote article 27).The opinions of consumers are varied. Consumers advocating for increasing services supporting natural birth project positivity around women's ability to give birth with minimum intervention in a safe environment. The consumers represented in 'The Age' survey appear fearful, unsure of what is best, placing their trust in health professionals to keep them safe. There is evidence to indicate the presence of the 'what is must be best' belief where the public values the status quo over options for which they have little experience ,41.Contrasting discourse were generated in this study; ''women are the experts in giving birth, trust our bodies to keep us safe', 'Australia is one of the safest countries in which to give birth or be born, what is must be best'. Selected statements illustrating the meanings of these discourses included:'While most mothers were generally satisfied with their experience of the maternity system, hundreds of women felt that both public and private maternity wards are overcrowded, needed more midwives, performed too many unnecessary medical interventions and did not provide enough non-drug options for pain relief' (quote article 18)'A lack of obstetricians available after hours means junior registrars are making critical decisions, often bad ones'. I was not supported well enough to have a vaginal birth. I felt like they were more concerned with getting me in and out quickly so they could free up the beds (quote article 19).Consumer opinion reported in newspaper articles on the issue of midwifery -led maternity services including home birth was sought from consumer organisations advocating for non obstetric -led services, supporting women to give birth safely with minimal intervention . Consume'Over 400 submissions to the national review from consumers, the majority requesting greater access to home birth cannot be ignored any longer' (quote article 24).'You seem to have left out the home birth option in your report. Provided the women is healthy, well informed and well supported, there is no reason she cannot give birth at home with the aid of a trusted midwife. My wife did so three times, 25 - 30 years ago (quote article 17).While most of the news articles are concerned with the exciting process of giving birth, consumer opinion raises the issue of private and public hospital care following birth. Traumatic experiences of new mothers left to care for their babies following caesarean surgery are described, as are distressing stories describing lack of support with breast feeding. Discourse generated in this study; 'recovering from the effects of surgery while struggling to mother my baby'. Selected statements illustrating the meanings of these discourses included:'Thirty per cent of women in postnatal care wards have had major abdominal surgery and they are expected to try and care for a newborn baby' (quote article 9).'Nurses are not caring for women after caesareans properly because of overcrowding. Unless you scream the loudest you don't get looked after' (quote article 19).Expert opinion supplied by the ACM strenuously challenges the obstetric position that only they have the training and expertise to safely care for pregnant women. In each article the midwifery professional body challenges current obstetric practices leading to rising rates of medical intervention and culminating in an alarmingly high rate of caesarean section in healthy young women having their first baby. Discourse generated in this study; 'rates of medical intervention in Australia are too high', 'medical intervention is not without risk it comes with the potential for serious complications'. Selected statements illustrating the meanings of these discourses included:'We (midwifery professor) have consistently found that 30% of women report that their birth was traumatic; that they feared for their life or their baby's life. This is a very high figure. We also know that about 6% go on to develop post-traumatic stress disorder' (quote article 7).'Babies born by caesarean section are more vulnerable to asthma, allergies and infection because they miss out on receiving their mothers' good bacteria during birth. Babies delivered vaginally received protective bacteria as they pass through the birth canal (quote article 8).Reported midwifery opinion reinforced the desirability of midwifery -led maternity services designed to meet the needs of women as mothers. The ability to build a relationship with a known carer based on mutual respect and trust is promoted by advocates of midwives as the panacea for being able to control levels of fear, maintain feelings of being in control throughout the birthing process and being satisfied with the outcome of the experience .The discourses identified and described in this critical analysis of articles published in 'The Age' national newspaper present the general public with a quandary, what to believe? Careful reporting, inclusive of the range of often divergent expert opinion relevant to each news item, leaves the general public and consumers to evaluate the evidence, forming their own conclusions. The right to decide what to think rather than being told what to think reflects the neoliberal values of modern consumerism a situation supported by the Australian government encouraging women to empower themselves through informed decision making regarding maternity care . The risThe general public has been inundated with headline grabbing reports outlining the deficiencies of maternity service. Obstetric practices that are insensitive and a maternity service that is inflexible resulting in women feeling traumatised by the experience of giving birth have been sensationalised. Evidence presented suggests that maternity services are not meeting the expectations of consumers. Consumer discourses identified in this study; 'the interests of women and their babies must be the focus of maternity care, not the system and those who work in it', and 'maternity care options need to be expanded to allow women choice in the care they receive' are reflected in the primary maternity care agenda for change. However expert medical discourses: 'modern medicine knows best and women would be best served to listen to the experts'; 'the demonization of women who choose to give birth naturally', and 'at least you have a healthy baby' convey a very different message positioning women seeking non obstetric -led care options at odds with maternity care providers.The discourses describing consumer experiences of maternity care in public and private hospitals: 'next please, feeling depersonalised in the queue'; 'feeling vulnerable in the care of a parade of strangers'; 'expected to place blind trust in those who know nothing about me and still feel safe' captures the consumer experience of a fragmented maternity service care and subsequent distress associated with finding themselves in territory they never dreamed possible . Women aDespite the poor performance of maternity services on many levels the general public is reassured by Australia's record of safety in childbirth, a success attributed to modern medical advances. A claim contested by the midwifery profession  through The discourses of women living in rural and remote communities and strong consumer organisations representing the interests of these women have featured strongly in the proposed reform agenda ,47-49. RFindings from this critical discourse analysis revealed that Australian maternity services are being portrayed to the general public as an inflexible outdated service struggling to meet the needs of pregnant women and in desperate need of reform. The style of reporting employed in this newspaper involved presentation to the reader the range of expert opinion relevant to each topic, frequently involving polarised positions of the experts on the issue. As a result the general public are presented with a conflict, caught between the need for the changes that come with a primary maternity model of care and fear that these change will undermine safe standards. The discourse; 'Australia is one of the safest countries in which to give birth or be born, what is must be best', represents the situation where despite major deficiencies in the system the general public may be too fearful of the consequences to consider a move away from reliance on traditional medical -led maternity care.The authors declare that they have no competing interests.MM was responsible for the study conception, design, review and analysis of the literature and drafting of the manuscript. KF and YC made critical revisions to the paper for important intellectual content. All authors have approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/11/47/prepub


Phalangeal microgeodic syndrome is a rare bone disorder affecting the fingers of young children, originally described by Maroteaux in 1970.The aim of this case series is to present the clinical and radiological manifestations of three affected pediatric patients, and to illustrate the redundancy of additional investigations if the physician is aware of the disease.The details of three patients with phalangeal microgeodic syndrome are summarized in the table. Three boys presented before the age of 2 years with swelling of the digits of one or both hands. Further clinical examination and laboratory evaluation were normal. On radiological examination multiple small osteolytic areas with sclerotic lining and periostal reactions were visible in the phalanges of the affected hands. All cases were treated with a conservative approach and spontaneous resolution occurred within weeks to months.Phalangeal microgeodic is a rare bone disorder presenting with swelling of multiple digits yet alarming radiological signs. These manifestations can be misinterpreted as caused by an infectious, inflammatory or osteolytic condition and prompt clinicians to expand the diagnostic process with MRI or scintigraphic imaging and even biopsy. Timely recognition of clinical and typical radiological signs may prevent unnecessary investigations for this benign condition.


One major constraint upon the application of molecular crop breeding approaches is the small number of genes linked to agronomically desirable traits through defined biochemical mechanisms. Proteomic investigations of crop plants under abiotic stress treatments have identified many proteins that differ in control versus stress comparisons, however, this broad profiling of cell physiology is poorly suited to ranking the effects and identifying the specific proteins that are causative in agronomically relevant traits. Here we will reason that insights into a protein’s function, its biochemical process and links to stress tolerance are more likely to arise through approaches that evaluate these differential abundances of proteins and include varietal comparisons, precise discrimination of protein isoforms, enrichment of functionally related proteins, and integration of proteomic datasets with physiological measurements of both lab and field-grown plants. We will briefly explain how applying the emerging proteomic technology of multiplexed selective reaction monitoring mass spectrometry with its accuracy and throughput can facilitate and enhance these approaches and provide a clear means to rank the growing cohort of stress responsive proteins. We will also highlight the benefit of integrating proteomic analyses with cultivar-specific genetic databases and physiological assessments of cultivar performance in relevant field environments for revealing deeper insights into molecular crop improvement. Figure 1).Analyses by agricultural researchers and humanitarian organizations have continually found that abiotic stresses such as drought, extreme temperatures, and unfavorable soil conditions are responsible for significant decreases in crop yield and can have adverse economic and nutritional consequences for local populations . Given tCellular physiology is underpinned by the composition and function of the proteome, and the power of proteomics techniques lies in their ability to quantitatively analyze large numbers of proteins in parallel, providing rich sets of information with which to explain the molecular mechanisms that underpin cellular function. The plant proteomics literature is characterized by two major threads. The first is the descriptive cataloging of which proteins are expressed in which tissue , localizHowever, the value of the above mentioned approaches as gene discovery and ranking strategies for future crop improvement is less clear. Many limitations of the approach and results derived from these experiments must be taken into account before committing to pursue any one protein in a molecular breeding program. First is the common observation that a small subset of the stress responsive proteins are repeatedly identified across a number of different stress experiments, the so called “déjà vu” phenomenon . While tWe propose that controlled environment experiments that attempt to mimic field conditions are best framed as a starting point to identify proteins of interest. The results of these studies then need to be added together and explored more widely by subsequent profiling experiments conducted under field conditions in the target environment, to determine which, if any, of the favorable molecular mechanisms uncovered in the laboratory hold true in the target environment and what are the relationships between them.Medicago  is highly suited to high sample throughput of a wider group or groups of proteins in a single analytical run, thus enabling a larger number of data points on different proteins to be gathered per unit of machine time. This is particularly useful for the assessment of protein changes in field-grown crop plants where the variation in the samples may be larger than those collected in the controlled laboratory environment. This also allows the relationships between changes in the abundance of different proteins to be explored in G × T datasets. Usually within the lab, power analysis will reveal that three to five samples are sufficient for the experiment to be informative and this number is amenable to quantitative shotgun proteomic approaches. However, field analysis may require >20 samples for the experiment to be informative and this would led to prohibitively expensive and time-consuming analysis by shotgun proteomic approaches. In these circumstances SRM MS approaches provide an opportunity to quantitate a select group or groups of proteins from a larger number of samples relativity cheaply and quickly. For instance, research suggest that the proteins involved in reactive oxygen species (ROS) detoxification are strongly linked to abiotic stress tolerance , but a fThe central difference between SRM MS approaches compared to other proteomics methodologies is the necessity for prior knowledge of proteotypic peptides derived from a protein of interest. Therefore, the most pressing constraint upon SRM approaches in crops is the lack of proteotypic peptides which can be used to quantify proteins of interest in relevant species, meaning that the first step in any SRM investigation involves a long period of library generation, where discovery proteomics and database searching are conducted to define high-quality peptides which are suitable for subsequent SRM experiments. This contrasts with the current state of the SRM field in other species, where for example the SRMAtlas project is collating representative mass spectra for signature peptides derived from tens of thousands of proteins expressed in human, yeast, and mouse . This daDespite widespread interest in applying molecular techniques to phenotyping crop plants, difficulties in sequencing the large and complex genomes of many crop species have constrained the power of proteomics applied to crops. DNA sequencing technologies are increasing the speed and decreasing the cost of sequencing, with recent highlights being the generation of reference genomes for barley  and tomaProteomics research is typically conducted by scientists trained in the disciplines of biochemistry and molecular biology. Their emphasis upon molecular mechanisms is indispensable for understanding the biological meaning of proteomics data. However, due to the specialist knowledge and logistical difficulties inherent in designing and conducting meaningful field experiments, proteomics researchers will likely depend upon collaborations with agriculturally focused researchers in order to access tissue grown in the relevant field environment with appropriate spatial designs and checks. Therefore, building effective collaborations across discipline boundaries is crucial for proteomics researchers who wish to access field-grown material and contribute to crop breeding programs. It can be argued that a mutual appreciation of classical plant physiology is the key bridge between molecular and field researchers, as its emphasis upon dissecting a specific trait at the single plant level is a logical convergence point for ideas and hypotheses stemming from the two different scales . For insAs claimed by the introductory sections of many papers, as well as preambles to many grant applications, the strategic endpoint of much plant biology research at the molecular scale is to improve the abiotic stress resistance of crop species. However, much of the data produced by plant proteomics research is yet to be actually evaluated for its use in directing breeding programs. Although the initial identification of candidate proteins linked to stress tolerance will still utilize discovery proteomics workflows applied to plants grown under controlled environment conditions in the lab, the technical capabilities of SRM are a better match for validation studies which aim to quantify the abundance of selected target proteins. The ability of the SRM approach to accurately quantify the abundance of a range of target proteins against complex cellular backgrounds in a large number of field-grown samples is a key to its applicability and value. Therefore, we argue that the judicious development of this SRM approach will further our understanding of the causative links between cellular composition and whole plant stress tolerance, and bring the knowledge and skills of proteomics researchers closer to the stated goal of crop improvement for higher yields in harsh environments.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Neurons in the mammalian cortex have conduction latencies that can scale up an order of magnitude or more with myelination and axon radius. These latencies can be categorized into two groups: distance dependent latencies associated directly with axonic/dendritic length and distance independent latencies due to intrinsic delays on synapses themselves. This paper focuses on the distance dependence of conduction latency, attempting to elucidate its effects on the temporal ordering of the network activity patterns. We use various statistical measures to characterize the temporal patterning behavior of the networks: mean phase coherence, a pairwise measure of phase locking between neuron spike trains averaged over the network and synchronous bursting, which quantifies the coincidence of spikes as it deviates from a Poisson process.We find that distance dependent delays and distance independent delays can lead to significantly different spatio-temporal patterning of network wide activity. The introduction of distance dependent delays into the network can drive temporal dynamics toward a more synchronous state. This synchronization enhancement can decrease as the topology of the network shifts towards a random graph and as the conduction speed moves out of an optimal range.


Alcohol consumption and affordability in the UK has increased over the last 50 years and is associated with a range of adverse oral health outcomes, the most serious of which, oral cancer, is also increasing in incidence. Despite this, routine alcohol screening and brief intervention (SBI) within general dental practice remains uncommon. This review of the literature examined the background and evidence base for undertaking alcohol SBI in general dental practice, including the rationale behind it and the range of issues related to it. Questions addressed include why alcohol consumption is of relevance to dental professionals; what policy context exists for the role of prevention and health promotion in dentistry; what screening tools are appropriate for use within a general dental practice; what evidence of efficacy is there for alcohol SBI in general dental practice; and what barriers and facilitators must be considered before alcohol SBI can be successfully implemented in this setting. We conclude that alcohol SBI in general dental practice, delivered as part of a multidimensional approach to tackling risky alcohol consumption, offer significant potential to improve the oral and general health of the population.


The identification and analysis of repetitive patterns are active areas of biological and computational research. Tandem repeats in telomeres play a role in cancer and hypervariable trinucleotide tandem repeats are linked to over a dozen major neurodegenerative genetic disorders. In this paper, we present an algorithm to identify the exact and inexact repeat patterns in DNA sequences based on orthogonal exactly periodic subspace decomposition technique. Using the new measure our algorithm resolves the problems like whether the repeat pattern is of period


Over the last 40 years the assessment and treatment of chronic obstructive pulmonary disease has focused primarily on airflow obstruction with little significance given to the problem of cough. The reasons for this include a view that cough arises simply from the direct irritant and inflammatory effect of cigarette smoke or the presence of excess mucus in the airways. Doubt that cough is of any consequence to patients or responsive to current therapies has reinforced this opinion. At odds with this is the emerging evidence that cough impacts adversely on patients’ health status and forms an important component of recently validated quality of life instruments. This article presents the arguments why the assessment and treatment of cough should have a more prominent place in the clinical management of COPD. Chronic obstructive pulmonary disease (COPD) is now recognised to be a condition of global importance in terms of its impact on the morbidity and risk of premature death of millions of people. The definition of COPD continues to be refined. HoweverThe role of cough in COPD has been well reviewed before. That reWe do not have good data about the frequency with which smokers cough. This reflects one of the major problems in cough research – the lack of simple metrics which describe coughing. How often should the subject cough and with what intensity before it is classified as significant? This Gordian knot was cut by the Medical Research Council in the 1960’s when they developed an epidemiological definition of chronic bronchitis. They haThis analysis was accepted for much of the last 3 decades but there are now reasons to doubt it. Coughing is associated with airway inflammation in non-smoking asthmatics and there are objective data showing persistence of airway inflammation in ex-smoking COPD patients, likely The epidemiological definition of chronic bronchitis emphasised the association with sputum production and it seemed reasonable to assume that excess mucus accumulation was the main factor driving cough in COPD. This agreed with pathological observation by Reid and Heard of mucous gland hypertrophy in the central airways of patients dying with what we now term COPD. Loss ofThe realisation of the association between self-reported cough and deaths from bronchitis led to the ‘British hypothesis’ that disease progression in COPD was related to the presence of bronchitic symptoms. This was tested in the long term study of lung function, symptoms and mortality in British postal workers which failed to find any association with disease progression and bronchitis. CoupledWhile there is no doubt that breathlessness is the most dramatic and disabling symptom experienced by COPD patients, more recent data shows that cough is also a matter of concern. Danish data in a large population study found that the presence of chronic mucous hypersecretion increased the risk of having pneumonia and was associated with a faster decline in lung function in men. More reThe impact of cough on patient well being has now been evaluated. In a telephone survey of 2950 COPD patients Kessler et al. found that cough was reported by 55% of subjects with 20% rating it severe to extreme. These sCough is now considered, along with breathlessness and sputum production, to be one of the cardinal symptoms of COPD and whicAt present it is difficult to quantify the degree to which cough responds to treatment for COPD. In part this reflects the lack of focus on cough in clinical studies where most attention has been paid to the relief of breathlessness or the prevention of exacerbations. However the lack of a validated measure of cough intensity and frequency which is known to respond to interventions is also a factor. This situation may improve when newer instruments such as the CAT and EXACT questionnaires are studied in treatment trials.There is general agreement that COPD patients who stop smoking are less likely to report the symptom of cough although this change may be more evident in the earlier stages of the disease, when lung function improvement with treatment is more evident. The proportion of patients with mild-moderate COPD who report a chronic cough declines by about 5% over a 5 year follow up period but only 10% of similar patients who quit complain of cough 5 years after stopping. WhetherMany pharmaceutical studies of COPD treatment have recorded cough as a symptom in daily patient diary cards but have seldom analysed the resulting data. One example of this is presented in Table In summary it appears that the presence of cough with or without sputum is an early feature of clinical COPD that helps identify people at risk of progressive disease. The cough reflex in COPD is increased to levels seen in current smokers even when the patient no longer smokes. Cough remains a key symptom in the diagnosis of COPD and its presence helps identify those patients at greatest risk of future exacerbations. Smoking cessation early in the natural history of the disease remains the most effective way of reducing cough but other therapies show some promise. Non-specific cough suppressants do not appear effective in COPD and should be avoided. What is really needed is a more systematic study of this important symptom in larger numbers of well characterised patients using validated ways of assessing the occurrence and impact of cough. Once we better understand the nature and variability of this symptom at a patient level then we will be able to develop more effective methods of managing it in clinical practice.COPD: Chronic Obstructive Pulmonary Disease; C2: Concentration of capsaicin inducing 2 coughs; C5: Concentration of capsaicin inducing 5 coughs; CAT: COPD Assessment Test; EXACT-PRO: EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): a patient-reported outcome (PRO) measure; TRISTAN: Trial of Inhaled Steroids and long-acting β2 agonists Competing Interests.The author declares that they have no competing interests.


The present issue focuses on the classic question of early vs. late selection and evaluates the current status of the perceptual load theory that has been offered as an intermediate solution. Several of the papers compare or contrast perceptual load with an alternative explanation- perceptual dilution. The first group of papers report evidence that is inconsistent with the perceptual load theory but is generally consistent with the dilution theory.Roper and Vecera  report tMevorach et al.  tested pChen and Cave  further In their opinion paper Linnell and Caparos  argue thMore evidence for a strategic component in the seemingly automatic processing of task-irrelevant information comes from Biggs and Gibson . They shThe review of Scalf et al.  presentsThe remaining papers use perceptual load theory as a direct or indirect context for studying other aspects of attentional selection. The role of working memory in regulating the degree to which distractors can be ignored is the focus of de Fockert's  review. Forster  takes thParks et al.  used SSVSwallow and Jiang  bring inFolk  makes anFinally, Moher et al.  tested sWe hope you will find this Research Topic interesting and informative. Enjoy your reading!


This reductionist approach has lead to many fundamental insights into how myosin powers muscle contraction. In addition, nature has provided scientists with an array of muscles with different mechanical properties and with a superfamily of myosin molecules. Taking advantage of this diversity in myosin structure and function has lead to additional insights into common properties of force generation. This review will highlight the development of the major assays and methods that have allowed this combined reductionist and comparative approach to be so fruitful. This review highlights the history of biochemical and biophysical studies of myosin and demonstrates how a broad comparative approach combined with reductionist studies have led to a detailed understanding of how myosin interacts with actin and uses chemical energy to generate force and movement in muscle contraction and motility in general.Striated muscle is an elegant system for study at many levels. Much has been learned about the mechanism of contraction from studying the mechanical properties of intact and permeabilized (or skinned) muscle fibers. Structural studies using electron microscopy, X-ray diffraction or spectroscopic probes attached to various contractile proteins were possible because of the highly ordered sarcomeric arrangement of actin and myosin. However, to understand the mechanism of force generation at a molecular level, it is necessary to take the system apart and study the interaction of myosin with actin using  The mechanism of muscle contraction has been one of the great biological questions and has occupied the attention of many scientists for much of the last half of the 20th century through to today Huxley, . With it2 cross sectional area along with the EM measurements of 500 thick filaments/μm2 muscle cross sectional area and about 150 myosin molecules per half sarcomere lead to a forces of about 4 pN per cross bridge. Since only one third to one half of the cross bridges were attached during an isometric tetani, the estimate of force per attached cross bridges about is 8–12 pN ? In which ways do the physiological ensembles of myosins affect the kinetics and production of force by the individual force generators?Historically, the muscles of frog and rabbit were primarily used for physiological and mechanical studies. These tissues were readily available and could be easily isolated from the animals. With the proper supply of metabolic energy in an oxygenated and buffered extracellular solution the contractile behavior of the muscle tissue could be reproducibly studied and maintained in a viable state for several hours. Comparative approaches were used to study the differences between fast and slow muscle fibers from within a single animal and between muscles of different animals Barany, . AlthougStudies to biochemically define muscle proteins in solution began with the purification of myosin and actin. Albert Szent-Gyorgyi showed that when an actomyosin solution at high ionic strength was exuded into a solution of lower ionic strength, “threads” were produced which contracted upon the addition of ATP  and regulatory (RLC) light chain in 1993  to drive the expression of wild type and mutant myosins. The ability of these cells to express mammalian myosins was variable. Several myosins such as smooth muscle myosin II  residue in switch 1 that forms a hydrogen bond with a glutamic acid residue (E459) in switch 2 to close the nucleotide binding pocket to permit catalysis. Mutation of either of these residues to an alanine greatly inhibits the actin-activated ATPase activity and abolishes the ability of the myosin to move actin filaments  to even an alanine (replaced of R = H vs. R = CH3) uncouples actin-activated ATP hydrolysis from motility  was discovered by Montell and Rubin  showed it to be single-headed without a long tail  was but one member  of actomyosin complexes has provided a link between the crystal structures and the geometry of myosin bound to actin (Rayment et al., A working stroke in two sub-steps was first seen in single molecule optical tweezer experiments with unconventional myosin I (Veigel et al., in vitro. Despite this kinetic difference both myosin V and myosin II molecules cycle through weakly and strongly attached actin states during their cycle which helps validate the use of myosin V as a model to understand the function of myosin II.Many of the biochemical properties that we have described for skeletal muscle myosin II so far make it difficult to study its interactions with actin at a biochemical and electron microscopic level. In the presence of ATP a myosin II head spends most of its kinetic cycle detached from and interacting only weakly with actin so that the lifetime of its strongly bound states are short. However some of the unconventional myosins serve as cargo transporters and have evolved to spend most of their kinetic cycle bound strongly to actin. An example is myosin V which, in melanocytes serves to aid in the transport of pigment granules, termed melanosomes, to the tips of the dendritic processes (for review, see Hammer and Sellers, These biochemical properties make myosin V much more amenable to study biochemically, particularly at the single molecule level, than most other myosins and it can be argued that it is the best understood myosin in terms of its mechano-chemical properties (Sellers and Veigel, in vitro motility assay, actin filaments are bound to the coverslip surface and fluorescently labeled myosins are in the solution. When a labeled myosin V molecule contacts the actin filament a processive run ensues that can be followed to determine the run length and velocity (Sakamoto et al., The processivity of myosin V can also be observed in a variant of the sliding actin motility assay where one inverts the geometry of the proteins used in myosin II sliding filament assays. In the single molecule myosin V Electron microscopy of myosin V molecules trapped while moving along actin demonstrated that the molecule bound to actin via both heads and that the two heads were separated by 36 nm (Walker et al., Bifunctional attachment of fluorescent probes to a single calmodulin moiety in the lever arm of myosin V allows for detection of the lever arm angular position during processive movement (Forkey et al., Dictyostelium myosin mutant in which the native lever arm was entirely replaced with an artificial one made up of a rigid section of sequence from α-actinin (Ruff et al., Several mutagenesis experiments support the idea that the light chain binding neck region acted as a lever arm. In these studies the neck regions of smooth muscle myosin II and myosin V were engineered to be longer or shorter than wild type via manipulation of the number of IQ motifs (Warshaw et al., The question of chemo-mechanical coupling is a crucial one in muscle research. Although most researchers would agree that one ATP molecule is hydrolyzed per power stroke and that load affects the kinetics of the cycle, the details of the chemo-mechanical energy conversion are not fully characterized. Here again, a reductionist approach, often using myosins other than muscle myosin have provided critical information. These experiments revealed that the sensitivity to load is very different in different parts of the cross bridge cycle. Studies of the load dependence of the chemo-mechanical cycle have been performed on striated muscle and smooth muscle myosin II (Veigel et al., The question of whether there is a tight coupling between cross bridge performance and ATP utilization was addressed in several studies. Ishijima et al. used optical trapping combined with fluorescence detection of cy3-ATP and came to the conclusion that skeletal muscle myosin II S1 might not have a tight one-to-one coupling between the mechanical and chemical cycles (Ishijima et al., There are many outstanding questions still remaining to fully understand muscle fiber mechanics. How do disease states alter cross-bridge mechanics? What are the rate constants for cross-bridges in isometrically contracting skeletal muscle fibers? How do the rate constants in the isotonically contracting muscle change and by how much as shortening velocity is altered? How do the rate constants in eccentrically contracting muscle change with rate of stretch and to what extent are the various populations of attached cross bridges altered? How are rate constants in contracting muscle altered by the extent of calcium activation or is the only change a rate in which the cross-bridges attach to exposed actin filaments? Finally a broad question, to what extent is skeletal muscles contractility altered by changes in diet, hormones, exercise, age, use, and innervations? It is clear how reductionist methods can address some of these questions. Several labs are using biophysical methods to probe myosins bearing mutations corresponding to ones found in diseased hearts (Palmiter et al., To understand how muscle works the vertebrate skeletal muscle systems has many advantages. However, the inability to make mutations within the myosin molecule in muscle, coupled with the fast and low duty ratio kinetics has made it challenging to understand the system at a molecular level. Using a comparative approach with recombinantly expressed non-muscle myosins, combined with a host of biochemical and biophysical techniques applied to purified myosin has allowed researchers to unravel how muscle works at a molecular level.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The aim of this poster is to provide a rationale and critical overview of ‘Autologous Blood Injection Therapy’ a new and possibly superior treatment modality in the management of tendinopathy. The theoretical background will be appraised including its clinical application and perceived clinical effectiveness.literature review and critical appraisal of papersAutologous blood injection therapy has been shown to have a significant positive effect on both pain and joint function, with concomitant therapies not being demonstrated to be required in the management of tendinopathy. However, the majority of studies were representative of patients being treated for refractory epicondylitis with different procedure techniques being employed. No studies compared blood re-injection therapy with dry needling alone, with minimal data available from controlled studies preventing a placebo response from being ruled out.With current evidence on the efficacy of autologous blood injection therapy in the management of tendinopathy being insufficient in quantity and quality, the current National Institute for Health and Clinical Excellence guidelines state this procedure is to only be used with special arrangement. Future research should focus on randomised control trials that clearly describe previous or adjunctive therapeutic interventions with a minimum follow up of 1 year.


The incidence of malignant melanoma (MM) continues to rise in the UK and Europe. Despite being a common form of skin cancer it is responsible for the majority of skin cancer related deaths. Around 3-15% of all cutaneous MM arise on the foot. However, lesions arising on the foot hold a poorer prognosis than melanoma elsewhere due to frequent misdiagnosis and late presentation. Initiatives to raise practitioner awareness to the problem would hopefully facilitate earlier referral and diagnosis.Following discussions with the Faculty of Podiatric Medicine and General Practice, a panel including Dermatologists (with an interest in skin cancer) and a Podiatrist was assembled and undertook a project to produce a guide for Chiropodists/Podiatrists on the early recognition of malignant melanoma arising on the foot.Following a systematic review of published evidence and existing guidelines it was concluded there was insufficient research to fully inform such a guide. Therefore using the available literature and case reports a paper was drafted using expert opinion and clinical experience. Evaluation of reported cases of misdiagnosis and clinical features lead to the development of a new acronym specific to foot malignancy with clinical information and suggested actions. In addition, specific advice has been drafted on nail melanoma highlighting common clinical features and differential diagnosis.The guide is currently being field tested amongst practitioners but should ultimately be available to all Podiatrists and Chiropodists to help raise awareness of this aggressive and often fatal disease.


An algorithm to automatically identify and extract matched molecular pairs from a collection of compounds has been developed, allowing the learning associated with each molecular transformation to be readily exploited in drug discovery projects. Here, we present the application to an example data set of 11 histone deacetylase inhibitors. The matched pairs were identified, and corresponding differences in activity and lipophilicity were recorded. These property differences were associated with the chemical transformations encoded in the SMIRKS reaction notation. The transformations identified a subseries with the optimal balance of these two parameters. Enumeration of a virtual library of compounds using the extracted transformations identified two additional compounds initially excluded from the analysis with an accurate estimation of their biological activity. We describe how the WizePairZ system can be used to archive and apply medicinal chemistry knowledge from one drug discovery project to another as well as identify common bioisosteres.


Whether the balance between integration and segregation of information in the brain is damaged in Mild Cognitive Impairment (MCI) subjects is still a matter of debate. Here we characterize the functional network architecture of MCI subjects by means of complex networks analysis. Magnetoencephalograms (MEG) time series obtained during a memory task were evaluated by synchronization likelihood (SL), to quantify the statistical dependence between MEG signals and to obtain the functional networks. Graphs from MCI subjects show an enhancement of the strength of connections, together with an increase in the outreach parameter, suggesting that memory processing in MCI subjects is associated with higher energy expenditure and a tendency toward random structure, which breaks the balance between integration and segregation. All features are reproduced by an evolutionary network model that simulates the degenerative process of a healthy functional network to that associated with MCI. Due to the high rate of conversion from MCI to Alzheimer Disease (AD), these results show that the analysis of functional networks could be an appropriate tool for the early detection of both MCI and AD. Graph theory provides valuable tools to describe the topological organization supporting cognitive processes On the other side, Mild Cognitive Impairment (MCI) is an intermediate state between healthy aging and dementia To our best knowledge, no previous characterizations of the topological properties of functional brain networks in MCI subjects with MEG were attempted so far. We here apply methods from complex networks theory to compute macroscopic and mesoscopic parameters of the functional networks in a group of nineteen MCI patients and a group of control participants of the same size. Brain activity was measured by means of MEG during a Sternberg's letter-probe memory task Materials and Methods in MEG scans were obtained from nineteen MCI patients and nineteen healthy volunteers during a Sternberg's letter-probe task (see The SL between the 148 sensors yields a (symmetric and weighted) 148As for the network parameters, the average degree of a node The node outreach In order to evaluate the deviation of the network parameters from their corresponding randomized versions, we have generated For each individual, we construct a probability matrix from the broadband signal The outreach parameter To compare the mentioned network parameters between the two groups, each parameter value was first averaged across epochs for each participant and channel pair. Then, nonparametric permutation testing From a holistic point of view, it is well known that the processing abilities of the brain rely on the segregation and integration of information Next, we have gone down to the lowest scale . We have used the classification of nodes introduced by Guimerà et al. All previous results indicate that mild cognitive impairment is related to a random increase in synchronization between brain areas. In order to model this phenomenon, it is necessary to understand how weights are distributed within the network, since the disease modifies the correlations between nodes. Our model can be discussed as follows: a) we randomly select a link in the correlation network Finally, The effect of MCI on brain networks dynamics is related to a group of phenomena that are hallmarks of an atypical network functioning. The relevant difference between healthy and MCI subjects is the increase in synchronized activity between brain areas. The enhancement in overall synchrony is reflected as an increase of average connectivity Another indication that this synchronization profile might be related to a compensatory effort is the fact that the main differences between the control and MCI subjects are observed in the alpha band  in order to see if this tendency of communication based on long distance connections could be ultimately assessed as an early hallmark of cognitive impairment.Many spatially distant, but functionally integrated functional networks have been described with fMRI and fcMRI analyses Finally, it is interesting to highlight the differences between the findings on MCI and Alzheimer disease (AD), since patients suffering from MCI are prone to develop AD. In both conditions, the distortion of the functional network is related to an evolution towards random structures, as indicated by a clustering coefficient and shortest path length that is closer to the random configuration. Both results are in accordance with the influence of aging in the increase of the network entropy, a concept recently formulated by Drachman File S1Supporting Information.(PDF)Click here for additional data file.


The needs for other modes of care apart from acute hospital care have long been realized but minimal integrated efforts have developed so far. Payment mechanism is a strong financing strategy to create favorable changes in the health systems.This session is to illustrate the rationale and progress of the developments of sub-acute and non-acute Casemix classification as a financing mechanism in Thailand.Review of literature of the last five years is the main data collection.The rehabilitative medicine has been an established discipline for over four decades in Thailand while psychiatry even longer. Complaints from health care providers of being underfunded activities have been around since the third revision of Thai Diagnosis Related Group since 2001. The fifth revision of TDRG set the goal of accomplishing other Casemix classifications apart from DRG for acute inpatient care, two Casemix systems for inpatient psychiatric and rehabilitative care were submitted to the National Health Security Office in 2011. The NHSO anticipated the difficulties of implementing the two new Casemix systems as initiative payment methods. Two separate streams of putting the Casemix products to the health systems were designed. Further follow-ups of these developments are needed to document knowledge generation related to health system outcomes via financing initiatives.Health finance and Casemix research need long-term commitment of a development team to refine results to find ways of implementing into health systems as well as to evaluate whether favorable changes happen.


Cardiac involvement infrequently occurs in hypopituitarism, and lethal cardiac arrhythmias are rarely reported. We present a middle age female who died as a consequence of refractory ventricular arrhythmia whose medical history and previous laboratory investigation were consistent with hypopituitarism. We conclude that hypopituitarism may lead to electrocardiographic changes and malignant ventricular arrhythmia and should be included in laboratory investigation and differential diagnosis of patients presenting with long QT syndrome Hypopituitarism is considered when a defect in some of the anterior pituitary axes results in failure of one or more target gland. The insult to the pituitary and hypothalamic area may be acute or chronic hence the clinical presentation may vary accordingly and in the majority of cases, it intervenes with a normal quality of life and may decrease life expectancy secondary to atherosclerotic complications or cerebrovascular accidents . Among vA 58 year old female lost consciousness in her room while preparing for a wedding ceremony and was instantly brought to the emergency room in 28.10.2010.Her cardiac monitoring on arrival showed polymorphic ventricular tachycardia degenerating to ventricular fibrillation, which was unresponsive to prolonged CPR efforts, and she died one hour after arrival to ER(emergency room. Examinations including electrolytes and blood sugar was reported to be normal, retrospective questioning of close family members and reviewing the previous medical data revealed that during last 36 months she had frequent visit to her family physician complaining of weakness and vertigo, her work up on 12 March 2007, while taking Levothyroxin100 ug daily and occasional 5 mg Prednisolone tab  revealedHypopituitarism was first described in 1914 by the German physician Dr Morris Simmonds (since then an enormous growth of knowledge about the pathophysiologic and management of this condition have been developed but the vague clinical presentation is still an obstacle to timely diagnosis and proper management which sometimes leads to extreme and unusual morbid presentations as seen in our case.Sudden unexpected death  and CardWe described a case presented with refractory ventricular tachycardia unresponsive to medical therapy with subsequent laboratory finding in favor of neglected panhypopituitarism. It is concluded that cardiac arrhythmia as a rare presentation of neuroendocrine disorders should be considered in differential diagnosis of long QT syndrome and ventricular arrhythmia.


Patients with systemic lupus erythematosus (SLE) have up to a 50-fold increased risk of developing atherosclerotic cardiovascular disease that cannot be explained by the Framingham risk equation. While both SLE-specific and nonspecific mechanisms have been proposed to play a prominent role in the induction of premature vascular damage in this disease, the exact etiology remains unclear. We have proposed that an imbalance between vascular damage and repair probably induced by IFNα and other type I interferons could play a prominent role in the induction of accelerated atherosclerosis in SLE. Our group and others have recently elucidated the potential role that these cytokines play in the development and progression of premature atherosclerotic disease in SLE and, potentially, in other autoimmune diseases. More recently, a novel role for aberrant neutrophils in the development of autoimmune responses and vascular damage in SLE and other diseases has emerged; in particular, the role that neutrophil extracellular traps may play in the development of this disease and its vascular complications such as endothelial dysfunction and atherothrombosis. The recent description of a distinct subset of proinflammatory neutrophils isolated from lupus patients that induces vascular damage and synthesizes type I interferons has shed new light into a potentially important cell subset implicated in endothelial damage. Finally, novel discoveries pertaining to the interactions of lipoproteins and the immune system may prove quite informative in understanding how premature atherosclerotic plaque develops in lupus.


In the last twenty years, several global targets for protection of marine biodiversity have been adopted but have failed. The Convention on Biological Diversity (CBD) aims at preserving 10% of all the marine biomes by 2020. For achieving this goal, ecologically or biologically significant areas (EBSA) have to be identified in all biogeographic regions. However, the methodologies for identifying the best suitable areas are still to be agreed. Here, we propose a framework for applying the CBD criteria to locate potential ecologically or biologically significant seamount areas based on the best information currently available. The framework combines the likelihood of a seamount constituting an EBSA and its level of human impact and can be used at global, regional and local scales. This methodology allows the classification of individual seamounts into four major portfolio conservation categories which can help optimize management efforts toward the protection of the most suitable areas. The framework was tested against 1000 dummy seamounts and satisfactorily assigned seamounts to proper EBSA and threats categories. Additionally, the framework was applied to eight case study seamounts that were included in three out of four portfolio categories: areas highly likely to be identified as EBSA with high degree of threat; areas highly likely to be EBSA with low degree of threat; and areas with a low likelihood of being EBSA with high degree of threat. This framework will allow managers to identify seamount EBSAs and to prioritize their policies in terms of protecting undisturbed areas, disturbed areas for recovery of habitats and species, or both based on their management objectives. It also identifies seamount EBSAs and threats considering different ecological groups in both pelagic and benthic communities. Therefore, this framework may represent an important tool to mitigate seamount biodiversity loss and to achieve the 2020 CBD goals. Deep-sea and open ocean waters are the largest and yet least understood environments on Earth One of the major challenges in designing and implementing governance and management strategies in these environments is the fact that deep seas and open oceans frequently fall in areas beyond national jurisdiction (ABNJ). Therefore, international commitments are necessary to undertake effective conservation actions. In the last twenty years, several global meetings on biological conservation and sustainable development have proposed to set aside for protection 10–30% of all the marine biomes  by the year 2012. The failure in meeting these objectives has been internationally recognized with just 1.17% of the world’s oceans currently included in marine protected areas (MPAs) mostly located in coastal waters www.gobi.org). However, the patchy nature of biological and ecological data regarding deep and open ocean ecosystems hinders a systematic application of these criteria and implies a wide reliance on global models and remote sensed data The methodologies suggested by the CBD should not be restricted to ABNJ and could also be adopted and implemented within areas of national jurisdiction. Pilot studies have identified several potential EBSAs in different marine regions  that capture the most relevant pelagic, benthopelagic and benthic components of seamount ecosystems. The presence of such indicators can be assessed by both using real data coming from sampled features or global models which could complement data deficient sites.http://www.gobi.org/candidate-ebsas). The presence of endemic organisms to assess the level of faunal uniqueness has to be considered with extremely caution, since seamount endemicity has been recently questioned The presence of hydrothermal vents on seamounts was used as a proxy for uniqueness. In fact, vents host a number of special communities and organisms that are found nowhere else in the marine environment e.g. Areas containing breeding or spawning grounds, juvenile habitat and important habitats for migratory species are considered good examples of this criterion The IUCN red list provides a comprehensive list of threatened, endangered or declining species sensuThis criterion values the degree of risk that will be incurred from human activities or natural events The dynamics of marine production in the open and deep oceans are poorly understood. To date, the depth of submarine features represents the best indicator of seamount productivity. In fact, shallow seamounts may intercept the diel vertical migration of zooplankton and micronekton, trapping these vertically migrating organisms and/or aggregate small zooplanktonic animals horizontally advected. This could result in an increased prey availability, which may benefit resident and visiting animals enhancing secondary production and aggregating behaviors Reliable estimates of biodiversity for seamounts are difficult to obtain with the data currently available in the scientific literature. However, the presence of structural species may increase local biological diversity and be used as a proxy for this criterion e.g. These are areas with a comparatively higher degree of naturalness as a result of the lack or low level of human disturbance Ten indicators were used to identify seamount EBSAs : four beIndividual indicators were weighted based on the relevance they have in the assessment of the EBSA criteria. Factors used to verify more than one criterion had a higher weight in the analysis . For exaThe major human activity currently impacting seamounts is fishing Mineral exploitation is likely to pose a serious threat to seamount ecosystems in the near future The effects of fishing and mining on individual seamounts were quantified using an expert knowledge system. This system was adapted from two recent reviews where experts were asked to rate the impact of several fishing gears on different taxonomic groups and habitats using a scale ranging from very low to very high The “threats score” of individual seamounts was determined by the anthropogenic activities occurring on that features. In fact, benthic, benthopelagic and pelagic seamount components will experience different levels of disturbance depending on the set of human related activities present. Among the set of fishing and mining practices present on a specific feature, it is possible to identify a subset of activities likely to pose the highest impacts to the different components considered . The final threat score was thus calculated as the average of the maximum impacts  posed toTo account for data uncertainty, data quality issues and the varying degree of knowledge regarding different seamounts and geographical area, a data uncertainty index similar to the one elaborated in Wallace et al. Two measures were incorporated in the index: a data quality index (DQ) and a data deficiency index (DD). Data quality reflects origin and nature of the collected data and was divided into three categories: low (scored as 1), medium (scored as 0.5), and high (scored as 0) data quality. Considering the wide nature of seamount studies, the definition of these categories was not very strict but was based on general guidelines. The high data quality category was designed to include information mainly derived from rigorous scientific surveys. Even though data included in this category should be predominantly quantitative, qualitative data may also be considered as high quality data if in great detail. Medium quality data are incomplete quantitative information or qualitative descriptions of EBSA indicators and human impacts present on individual seamounts. These data should always be specific to a particular feature and validated in the literature. Low quality data include undisclosed data regarding wide geographic areas which do not specifically address seamounts, information inferred from models or from different seamount properties or data not properly referenced. The detailed scoring standards used to assign the data quality scores to all EBSA and threat indicators are described in the supplementary information  and S3. The data uncertainty index is visualized as error bars in plots of the seamount EBSA likelihood scores versus human threats scores. Minimum and maximum values of each final seamount EBSA likelihood and human threats score are calculated by subtracting and adding the data uncertainty index. The error bars can therefore potentially range up to two units above and below the original score. In this manner, a seamount lacking data and/or with low data quality is shown as possibly belonging to different EBSA likelihood and threat categories, reflecting the uncertainty of the outcome.Protecting all seamounts is neither particularly rewarding nor practically feasible considering the high variation that exists in terms of their ecology, geophysics and potential human impacts and the large number of seamounts present in the world’s oceans. Therefore, approaches that systematically highlight conservation priority areas for seamount ecosystems can constitute a valuable tool for marine management purposes. We hereby propose an approach that combines the likelihood of a seamount constituting an EBSA and the level of human impact posed to a submarine feature to locate priority areas for seamount conservation at global, regional and local scales. This methodology allows the classification of individual seamounts into four main conservation categories, which can help in optimizing management efforts toward the protection of the most suitable areas. The portfolio categories are: Low EBSA likelihood-Low threats; Low EBSA likelihood-High threats; High EBSA likelihood-Low threats; High EBSA likelihood-High threats. EBSA likelihood and threats for individual seamounts can be easily summarized and graphically compared.Additionally this approach is designed in a way that helps in visualizing what parts of the ecosystems  are contributing to the EBSA score or being threatened by human induced activities. This is of paramount importance in identifying seamounts that may be ecologically or biologically significant for both the benthic and pelagic components of the ecosystem and in complementing preexisting conservation strategies with the protection of underrepresented seamount components.In order to test the framework developed here, we have randomly assigned the presence or absence of the ten indicators developed in the EBSA scoring procedure and of the nine types of threats considered in the threats scoring procedure to 1000 dummy seamounts . In this way it was possible to assess the ability of our framework to assign real world seamounts to the different portfolio categories considered. In addition, a set of eight seamounts from different geographical areas were selected as case studies for applying the present framework, six located in the Atlantic Ocean  and two located in the Gulf of Alaska (Cobb and Bowie seamounts). Data for the evaluation process were obtained by reviewing the existing literature The dummy seamounts were assigned to all 4 portfolio categories with only 5.1% seamounts considered as highly likely to be identified as EBSA with low degree of threat and 3.6% seamounts with low likelihood of being identified as EBSA with low degree of threat. Most of the dummy seamounts fall in the category low likelihood of being identified as EBSA with high degree of threat (36.2%) or high likelihood of being identified as EBSA with high degree of threat (55.1%). These results indicate that the framework is adequate to assign seamounts to different portfolio categories. In For the 8 case study seamounts considered, seamount EBSA likelihood scores  ranged fOverall, the eight seamounts evaluated were allocated to three different portfolio categories of EBSA likelihood and threat exposure : high liOf the case studies considered, Sedlo and Gorringe are those with the highest EBSA likelihood scores and, therefore, they may represent the most suitable areas where to adopt conservation measures. These two seamounts are experiencing very different levels of human pressure, with Sedlo presenting lower chances of detrimental effects caused by human activities than Gorringe. However, given the large uncertainty associated with the Gorringe threat score, a further evaluation of the activities should be undertaken. Sedlo has already been proposed as a suitable site for a marine protected area In order to achieve the conservation goals established under the Convention on Biological Diversity, scientists from different fields were asked to define and apply criteria which can highlight marine areas of particular interest The framework proposed here was designed to set priorities in seamount conservation and to help developing spatially explicit seamount management policies. In order to avoid the location of protected areas in places that contribute little to preserve ecosystem structures and processes, the biological or ecological value of specific areas should always be considered as a primary criterion for the identification of conservation priorities Three aspects were central in the practical definition of the proposed methodology. Our first concern was to develop a system which could provide solid measures of the relative value and threat status of individual seamounts. The choice of the selected seamount EBSA indicators and the definition of the most relevant human activities to seamount ecosystems were based on an extensive review of the existing literature and through intense consultations with seamount experts. This approach constitutes, therefore, a complete synthesis of what is presently known regarding seamount ecosystems. Our second concern was to design a system compatible with the data currently available. The major constraint faced by this kind of analysis is generally the scarcity of information readily available. In fact, while a very small portion of submarine relief has a fairly detailed ecological and biological description and an accurate report of ongoing anthropogenic activities, the large majority of seamounts have either never been explored or even charted through direct scientific measurements or only partially described The outcomes of the dummy seamounts may serve as an indication of the robustness of our methodology. Since our analysis was based only on presence/absence data, conservative outcomes regarding the threat status of individual seamounts should be expected. This is reflected in the outcomes of the analyses, where the highest proportion of seamounts fell within the high threat score category. Moreover, the consistent allocation of the dummy seamounts into high and low EBSA likelihood categories, as shown in Another important characteristic of this framework is that allows the identification of seamount EBSAs and threats considering different ecological groups in the pelagic and benthic realms . In bold the most conspicuous cold-water taxa.(DOCX)Click here for additional data file.Table S2Scoring standards used to assess the data quality of the EBSSA indicators.(DOCX)Click here for additional data file.Table S3Scoring standards used to assess the information quality regarding the human activities occurring at a seamount.(DOCX)Click here for additional data file.Information S1Guidelines for scoring human-induced threats to individual seamounts.(DOCX)Click here for additional data file.Information S2Description of the information used to evaluate the seamounts’ EBSA likelihood and threats.(DOCX)Click here for additional data file.


We describe a novel method for analyzing neural data that uses a combination of Markov transition matrices and Kullback-Leibler divergence to characterize spike history and spike patterns. For this method, the interspike intervals (ISIs) are divided into bins by quantiles, and a Markov transition matrix is computed for the ISI sequence. This Markov transition matrix is then compared to another Markov transition matrix constructed under the assumption of independent spiking. We then compute the Kullback-Leibler divergence between the distributions of ISI transition probabilities for each bin. The purpose of this method is to quantify the effects of spike history on neuron output and to help better characterize the flaws associated with assuming independent spiking.We test this method on both simulated data and experimental data from primary visual cortex of cats, publicly available through CRCNS -3. InterThese results emphasize that the main shortcoming of simple spiking models, like the Poisson model, is a failure to account for spike history and spike patterns related to bursting and long periods of silence. This also suggests that neural systems can gain an advantage in computational efficiency by accounting for spike timing aspects of bursting and extended periods of silence within the neural code.


Traumatic brain injury (TBI) represents one of the greatest unmet needs in medicine and public health ? Could this be perhaps that we still have insufficient knowledge of how degradation products from brain tissue are removed into the venous blood? Is this directly into the venous system, or indirectly by flow of the extracellular fluid draining via the cerebrospinal fluid into the sagittal sinus? Basic understanding of such mechanisms would be of great relevance toward optimal biomarker sampling. Whilst many studies on the prognostic value of biomarkers show clear prognostic effects, it should be realized that numbers in these studies in general are small and that the added value of biomarkers as prognostic indicators over and above other predictors has not yet been adequately shown in multivariable analyses. The concept of being able to differentiate between neuronal and glial injury based upon biomarkers is exciting. This topical issue will also address relations between laboratory markers and other biomarkers such as imaging modalities. By definition characterization and classification of brain injury is multidimensional. Better characterization with the aid of biomarkers can be expected to facilitate Precision Medicine, a concept recently advocated by the US National Academy of Science . Precisi


The costs of developing a probiotic or prebiotic ingredient have always been substantial. Ingredient characterization, evaluation of technological and physiological properties, and demonstrations of safety and clinical efficacy require expensive research. The demanding regulatory requirements imposed by EFSA raise the bar even higher so that the costs of acquiring the necessary clinical evidence to support labeling of these food ingredients is approaching that of pharmaceuticals. In order to justify investment in such expensive clinical development, companies require certainty that they can gain a return on investment. Patenting can provide some protection but is not always possible to patent ingredients, and the period of protection is limited. All ingredients eventually face the prospect of commoditization once patents expire. Branding strategies offer one means of maintaining adequate product differentiation to protect market share and margins over the long term.


Developing a sense of hope is a foundation for recovery. How can we inspire hope and motivation in those who are suffering from an eating disorder and the struggles that ensue?The Eating Disorder Mentor Program is a collaborative project between The Eating Disorder service at Royal Melbourne Hospital (ED-RMH) and Eating Disorders Victoria (EDV).It's an opportunity for people with a lived experience of an eating disorder to tell their recovery story and share their insight with current patients. Research has shown the many benefits of peer support which include increased feelings of hope for patients and the learning of practical strategies to assist their recovery. Mentors gain skill and satisfaction from seeing their lived experience used as a valuable source of expertise in promoting recovery.This presentation will:• Give an overview of the program including the aims, processes and results• Explore the value achieved by collaboration between a community based mental health provider and a specialist tertiary health service• Highlight the benefit of combining the experience of both health professionals and consumersCare in Inpatient and Community Settings stream of the 2013 ANZAED Conference.This abstract was presented in the


Microarray data acquired during time-course experiments allow the temporal variations in gene expression to be monitored. An original postprandial fasting experiment was conducted in the mouse and the expression of 200 genes was monitored with a dedicated macroarray at 11 time points between 0 and 72 hours of fasting. The aim of this study was to provide a relevant clustering of gene expression temporal profiles. This was achieved by focusing on the shapes of the curves rather than on the absolute level of expression. Actually, we combined spline smoothing and first derivative computation with hierarchical and partitioning clustering. A heuristic approach was proposed to tune the spline smoothing parameter using both statistical and biological considerations. Clusters are illustrated a posteriori through principal component analysis and heatmap visualization. Most results were found to be in agreement with the literature on the effects of fasting on the mouse liver and provide promising directions for future biological investigations.


Neuronal morphology plays an important role in the processing of spatiotemporal synaptic input patterns.We formulate a new cable theoretic model to study the output in a dendritic cable with many subtrees, both analytically and computationally. The model is an extension of the continuum spine model derived by Baer and Rinzel  and likeA multicompartment model with equally spaced discrete branches implemented in NEURON  is used For a passive membrane and uniformly distributed branches, this formulation provides analytic estimates of electrical parameters, such as the input resistance. Transforming the equations to the frequency domain, we examine the steady state response properties for periodic forcing, where the impact of structural properties on transfer properties and the phase shift at different locations are calculated directly. Based on calculations of the voltage response along the primary neurite, the continuum formulation performs much better than a simple cable as an approximation of the morphologically realistic model. Simulations of the continuum model are in good agreement with the realistic model for frequencies up to 1000 Hz.In insects neurons the spike initiation zone (SIZ) is usually located far away from the recording site. We use this model to investigate the impact of the location of the SIZ and morphology on spike initiation and spike shape at the recording site as well as on activation and inactivation curves of ion channels obtained by voltage clamp recordings.Also we investigate how structural properties impact the results found in a point model of MN5, where variations of ion channel densities in physiological ranges lead to different observed firing properties .


Hemolytic activity was within the acceptable range revealing low toxicity risk of nanoemulsion. The ex vivo release studies of the formulated nanoemulsions were carried out using sheep nasal mucosa in comparison with drug suspension in simulated nasal fluid. The results revealed that release rate was biphasic and faster from drug suspension as compared to nanoemulsions. It can be concluded that nanoemulsions were prepared successfully having low particle size and can be used to deliver curcumin and artemether intranasally for management of cerebral malaria. The efficacy of the developed formulations either alone or in combination was evaluated further for antimalarial efficacy in Plasmodium berghei ANKA murine model of cerebral malaria in comparison with pure drug suspension administered intranasally and intravenously and showed promising results.The objective of the present investigation was to explore the potential of nanoemulsion (NE) containing artemether-curcumin combination to accomplish the delivery of drugs to the brain via olfactory delivery system for management of cerebral malaria. The components for curcumin NE (C-NE) and artemether NE (A-NE) formulations were selected based on saturation solubility studies and were prepared by aqueous titration technique . The muc


Iranian Red Crescent Society is a charitable and non-profit organization playing an active role in public-benefiting and humanistic affairs and services offered for rescue operations. The prospect of this society has been mentions as Red Crescent Society should be accountable for all kind of events in all parts of Iran with the highest possible efficiency and with minimal time required for services. In the bSWOT as a guide can analyze factors affecting the competition between the organizations and companies while providing a prospect for the future. Therefor


Aspergillus fumigatus, an interesting and relevant morphotype beyond the conidial and hyphal stages has gained increasing attention: the multicellular biofilm. Such hyphal communities were first described for A. fumigatus in 2007   as important component of Aspergillus biofilms (Ramage et al., Aspergillus lifestyle but also provide perspective for improvement and new avenues in antifungal therapy or biotechnological applications.In the light of the clinical as well as industrial relevance of


Given the high prevalence and serious consequences of both CVD and mental disorders, associations between the two types of diseases would have a major impact on public health. If there is a causal link between CVD and mental disorders, the screening and early treatment of one of the two types of diseases is likely to have a preventive effect on the other pathology. The mechanisms underlying this co-morbidity is poorly understood, partially due to major limitations of existing studies such as the use of clinical samples, the lack of an appropriate comparison group, the use of psychiatric rating scales for a single psychiatric syndrome rather than structured diagnostic interviews, reliability on self-reported somatic information rather than objective measurements and a lack of simultaneous assessment of cardiovascular risk factors which does not allow the study of potential pathways from a specific mental disorder to cardiovascular disease.The CoLaus/PsychoLaus is a prospective follow up of participants in the CoLaus cohort to assess whether mental diseases increase vulnerability to cardiovascular disease/risk factors or vice versa and to identify common pathogenic processes involved. It also gives better knowledge about long term course of mental disorders and cardiovascular diseases and service utilisation patterns all of which can result in more effective strategies in prevention and treatment. Current evidence from CoLaus/PsyCoLaus suggests a significant role of a typical depression symptom, which are strongly associated to physical and behavioural cardiovascular risk factors.