Induction programme for trainee doctors in the UK generally do not focus on the surgical aspects of their jobs. In this context we decided to conduct a telephonic survey among the hospitals belonging to three orthopaedic training regions in the UK from the point of view of the diversity of instrumentations and implants used for index procedures.We chose four index trauma & orthopaedic procedures . A telephonic survey was done in six NHS trust hospitals which were part of an orthopaedic training rotation . In total there were 39 different instrumentation systems for these 4 index procedures in the 6 trusts (see table In view of this we feel that more focused theatre based induction programmes for higher surgical trainees is advocated in each hospital trust so trainees can familiarise themselves with the tools available to them. This could include discussion with the consultants and senior theatre staff along with representatives from the companies supplying the implants and instrumentation systems. Hospital induction programmes are a standard part of the commencement of new posts for junior doctors . It has To emphasise the scale of this problem a telephonic survey was done in six NHS trust hospitals which were part of an orthopaedic training rotation . In our survey we used 4 index operations commonly performed in all hospitals with a trauma and orthopaedic intake. For each trust we contacted (by telephone) the theatre manager to identify the instrumentation and implant systems used for total hip replacement (THR), total knee replacement (TKR), and fixation of tibial or femoral fractures with either intra-medullary nailing or external fixation.In total there were 39 different instrumentation systems for these 4 index procedures in the 6 trusts (see table This representative survey we conducted shows no uniformity in the orthopaedic instrumentation used between the different regions. This is hardly surprising as currently there is a vast array of instrumentation systems available in the market for use in orthopaedic surgery. Considering that this data only represents 4 particular index operative procedures the actual amount of different implants and instrumentation systems for each trust is likely to be significantly higher.We recommend mandatory theatre induction as a part of the specialist registrars' departmental induction programme. This could include discussion with the consultants and senior theatre staff along with representatives from the companies supplying the implants and instrumentation systems. Ideally it would include practical/video demonstrations of the commonest systems used, as well as a booklet for each trainee containing the operative technique for the instrumentation systems.The authors declare that they have no competing interests.AJSK designed the survey and wrote the article, JO and SKSW conducted the survey and the literature search, SP revised the manuscript and gave final approval for publication


The effect of varying the numbers  of weekly applications of DMBA to the dorsal skin of intact and castrate male and female rats on the induction of basal and squamous celled epitheliomas and of sarcomas has been investigated.Basal celled tumours originate mainly in hair follicles and squamous celled neoplasms in the interfollicular regions of the epidermis and differ in their progression to malignancy. Penetration of the panniculus carnosus is neither a sufficient nor necessary criterion of malignancy since growing hair follicles pass through the muscle layer and carcinomas and sarcomas which are still confined to the dermis, spread along the perineural lymphatics and metastasise to the lungs.Sex and castration do not affect carcinogenesis of epitheliomas in the dorsal skin at any dose level. Significantly more sarcomas result from 20 weekly paintings in male than in female or castrate rats.The induction period for all tumour types is shortened in sensitive individuals only by an increase from 5 to 10 weekly applications. For less sensitive animals the rate of oncogenesis is accelerated with number of administrations up to 20, but slowed down from this level by 40 paintings. The optimal dose for speed of induction of all tumour types, for maximal yield of basal celled epitheliomas and for that of sarcomas in male rats is 20 weekly applications.The progression to malignancy varies with tumour type: it is fast for sarcomas and slow for basal celled neoplasms. Of the 336 rats at risk only 1% have fibromas or other precursor lesions, while 40% have sarcomas; animals with squamous celled papillomas account for 12%, but those with carcinomas for 66%; there are, however, 64% of rats with basal celled papillomas and only 9% with carcinomas.The optimal dose phenomenon in carcinogenesis is discussed.


An in vitro agar colony technique has been developed for the growth of tumour cells taken directly from human tumours grown in immune-suppressed mice. The novel feature of the technique is the addition of a replenishable liquid phase which permits the maintenance of relatively slowly growing cells. A number of different xenografted tumours have been cultured successfully in this system, with red blood cells added to the agar and using 5% O2 in the gas phase. The technique has been used to assay cell survival in tumours treated in vivo with cytotoxic agents, and examples are given of survival curves obtained from a pancreatic tumours irradiated with gamma-rays and a colonic tumour from mice treated with cyclophosphamide. The results obtained by this in vitro method are in agreement with those from the agar diffusion chamber technique. This culture method has also been successfully used for the growth of cells taken directly from human tumour biopsy samples obtained in the clinic.


In drinking water supplies the intake of the toxic heavy metal lead is commonly due to metal corrosion in the peripheral water distribution system, especially the user’s plumbing or lead service lines. Recently, the problem again received attention in the United States when testing data of drinking water at schools was published . In EuroLead exposure from drinking water has been a topic of public health prevention programs in several parts of Germany before, for example, Hamburg  and FranA moderately higher percentage of households with elevated composite water samples was found in the geographic area of the city of Berlin using two composite water sampling methods  can have a substantial effect in elevating lead . Flushin


A crisis exists in medical education. Changes in methodology have diverted attention from synthesisto mass accumulation of factual data. The response to this crisis has been largely focused on a shellgame involving new pathways and curriculum changes without addressing the critical issue of whatconstitutes education. The ultimate problem in medical education is a crisis of leadership. Untileducation is given a priority status and the obligations to teach on the part of medical educators andto learn on the part of students are translated into a creative policy by those who can lead, the wheelsof learning will continue to spin without significant progress.


The early changes induced by a carcinogenic nitrosoquinoline compound (NTDQ) have been studied in the subcutaneous tissues of 88 rats. An initial acute infiammatory response is quickly replaced by a distinctive granuloma which is established by 10 days and persists indefinitely—a sequence which takes place both in adult and in newborn animals. Its main components—histiocytes, multinucleate giant cells and granulation tissue—are described in detail and the formation of giant cells by fusion from adjacent histiocytes has been traced. Autoradiographic studies with tritiated thymidine show heavy nuclear labelling in the histiocytes and fibroblasts during the first 10 days; this later declines but raised levels of nuclear labelling persist up to the end of the experiment. No proliferative activity is seen in the giant cells and these cells show only feeble phagocytic activity, tested by their ability to take up carbon particles. The experiments in which colloidal carbon was injected locally also provided some information on the lymphatic vessels in the vicinity of NTDQ-induced granulomata. It appears that, initially, the lesions contain large dilated lymphatic vessels. Later, a dense connective tissue barrier develops and lymphatic connections with the surrounding dermis are progressively reduced.The properties of granulomata induced by NTDQ are discussed and some possible relationships between the formation of granulomata and eventual tumour developed are considered. Particular emphasis is given to two related features: the sustained proliferative activity of the fibroblasts and the resulting semi-isolation of the injection site lesion by the formation of a dense connective tissue barrier.


Fluorescence probes for the active centre of an enzyme associated with tumour cells have been used to locate leukaemia cells in a model rat system. These fluorescent techniques are inexpensive and rapid to carry out. The leukaemic cells can be located by fluorescence microscopy in frozen sections, wax embedded sections and resin embedded sections. The technique is illustrated with reference to sections of leukaemic rat kidney, epididymis and testis. These studies confirm earlier histological findings employing conventional staining techniques and have the advantage that individual leukaemia cells can be detected in leukaemic animals undergoing drug therapy. The evidence suggests that these techniques will be of value in further studies of the design of drugs directed to leukaemia cells.


Cell survival was investigated in an intraocular retinoblastoma-like tumour 30 min to 48 h after photodynamic therapy. The survival of the cells was assessed by an in vivo to in vitro colony forming assay, estimated by either the plating efficiency of the treated tumour cells compared to non-treated cells or the number of clonogenic cells per mg excised tumour. Curves showing cell survival as a function of the time between light irradiation and excision of the intraocular tumours were biphasic. This suggests more than one PDT tissue destruction mechanism in vivo (i.e. an early direct cell damage plus a subsequent late damage occurring in the tumour tissue left in situ after treatment). The delayed mechanism may be due to changes in the environment of the tumours probably caused by vascular damage. Tumour cells sensitised by Photofrin II in vivo and excised from the eyes were damaged by light when irradiated in vitro and this was dependent on the light energy dose. This showed that cellular Photofrin II uptake in the eye tumours was sufficient for direct cell damage and thus supports the suggestion that direct and indirect tumour destruction occurs in this eye tumour after photodynamic therapy.


The serum concentrations of the radiosensitizer metronidazole have been determined in mice for both oral and intraperitoneal doses of the drug and these have been related to radiosensitization studies in murine tumour systems. In preliminary work before a possible clinical trail the serum metronidazole concentration/time curves have been determined in 7 patients using single doses of metronidazole of up to 15 g. The data suggest that a linear relationship exists between the metronidazole dose expressed in mg/kg and the peak serum concentration. The possibility of achieving radiosensitization of tumours in patients after tolerable doses of metronidazole is discussed in relation to enhancement ratios determined for in vitro and in vivo systems. It is concluded that predictions from in vitro systems give values that are probably too optimistic.


The alkylamines and their related boron derivatives demonstrated potentcytotoxicity against the growth of murine and human tissue culturedcells. These agents did not necessarily require the boron atom topossess potent cytotoxic action in certain tumor lines. Their abilityto suppress tumor cell growth was based on their inhibition of DNA andprotein syntheses. DNA synthesis was reduced because purine synthesiswas blocked at the enzyme site of IMP dehydrogenase by the agents. Inaddition ribonucleotide reductase and nucleoside kinase activities werereduced by the agents which would account for the reduced d[NTP] pools.The DNA template or molecule may be a target of the drugs with regard tobinding of the drug to nucleoside bases or intercalaction of the drugbetween DNA base pairs. Only some Of the agents caused DNAfragmentation with reduced DNA viscosity. These effects wouldcontribute to overall cell death afforded by the agents.


Resistance to FCE 24517 is not related to the emergence of any of the most frequently observed phenotypes. We have found that two resistant cell lines (L1210/24517 murine leukaemia and LoVo/24517 human colon adenocarcinoma) present congenital modifications in tyrosyl phosphatase and kinase activities. Moreover, the cytotoxic activity of FCE 24517 is increased in combination with a tyrosine phosphatase inhibitor and decreased in combination with protein kinase inhibitors, this being in agreement with the hypothesis that the activity of this drug is strictly dependent on the presence of tyrosine phosphorylated protein(s).


Laboratory robotics has been firmly established in many non-QClaboratories as a valuable tool for automating pharmaceuticaldosage form analysis. Often a single project or product line is usedto justify an initial robot purchase thus introducing robotics to thelaboratory for the first time. However, to gain widespread acceptancewithin the laboratory and to justify further investment in robotics,existing robots must be used to develop analyses for existing manualmethods as well as new projects beyond the scope off the originalpurchase justification. The Automation Development Group inAnalytical Research and Development is a team of analystsprimarily devoted to developing new methods and adapting existingmethods for the robot. This team approach developed the expertiseand synergy necessary to significantly expand the contribution ofrobotics to automation in the authors' laboratory.


Data from the Los Angeles County Cancer Surveillance Program (CSP) from 1972 to 1975 were used to study the descriptive epidemiology of testicular cancer and prostatic cancer. The very high black/white ratio and late age peak of cancer of the prostate contrasted sharply with the very low ratio and early age peak of testicular cancer. However, both sites had higher rates among upper occupational and social class groupings. Avalable descriptive and analytical research suggests that the etiology of prostatic cancer is most probably related to hormonal influences rather than to a horizontally transmitted agent, while the etiology of testicular cancer is most probably related to endogenous or exogenous hormonal influences in utero or in infancy, or to in utero exposure to other exogenous agents.


Similar animals were also treated with local hyperthermia . The marked increase in median survival time following the combination of drug and local hyperthermia indicates that the combined treatment has a synergistic effect in the control of solid tumours. The median survival time of animals receiving the two treatments in immediate succession was higher than in animals with 30 min between treatments. This has important implications for the therapy of human cancer.


The author discusses the implications of a new study that used data from The Netherlands to simulate the annual and lifetime medical costs attributable to obesity. PLoS Medicine, Pieter van Baal and colleagues used data from The Netherlands to simulate the annual and lifetime medical costs attributable to obesity . Governments need to understand that public-health policies affect more than merely the sum of individual health, and sadly require greater courage to implement than does treating the sick.


The potential of plants to replace fossil oil was evaluated by considering the scale of production required, the area of land needed and the types of plants available. High yielding crops (50 tonnes/ha) that have a high conversion efficiency (75%) would require a global land footprint of around 100 million ha to replace current (2008) oil consumption. Lower yielding or less convertible plants would require a larger land footprint. Domestication of new species as dedicated energy crops may be necessary. A systematic analysis of higher plants and their current and potential uses is presented. Plant biotechnology provides tools to improve the prospects of replacing oil with plant-derived biomass by increasing the amount of biomass produced per unit area of land and improving the composition of the biomass to increase the efficiency of conversion to biofuel and biomaterials. Options for the production of high value coproducts and the expression of processing aids such as enzymes in the plant may add further value to plants as bioenergy resources. Biomaterials and bioenergy have long been produced from plants. The development of oil from fossil fuel replaced many of these traditional uses during the twentieth century. The prospect of oil supplies being exhausted and concern about the impact on the atmosphere of adding the carbon in fossil fuels have resulted in renewed interest in the use of plants as direct sources of bioenergy and biomaterials .Humans domesticated plants more than 10 000 years ago largely for food . Use of The first generation of biofuel production has been based upon the conversion of the storage carbohydrates (sugars and starch) in the plants into fuel . Oil froA major question we need to ask is how much land do we need to grow plants to replace oil. The global consumption of oil in 2008 was around 3930 million tonnes. The area of land required can be calculated if we assume different levels of efficiency in converting plant biomass to biofuel  at any given yield of biomass per hectare. The next question we need to address is what species of plants do we have with yields that would allow production on a reasonable land footprint. The yields of crops used as biomass sources need to be achievable on a sustainable basis with minimal energy inputs for crop production including cultivation, planting, nutrient production and application, harvesting and transport. This requirement limits the choice of crop species and production environments.Panicum virgatum) has been widely evaluated as an energy crop option  are C4 plant with high yield potential. Sugarcane and related species are probably the grasses with the highest yield potential identified to date. Sugarcane has potential to yield in excess of 100 tonnes dry matter/ha/year . Switchgrass  conservation. The amount of arable land in the world has been estimated at more than 4000 Mha. The amount of land available by continent is given in Discovery of the best options for use as energy crops in specific environments requires an analysis of available species and their suitability in available production environments. A systematic analysis of plant options for food, energy, conservation and other uses should include all plant species. Those that do not have a current specific human use may have one in the future and all species contribute to biodiversity. Selection of new plants for energy production or even diversified food production requires a systematic analysis of the available options. Many of the species currently being promoted for use as energy crops have not been a product of such analysis and are in many cases not good options. For example, many oil-producing species are promoted because of the ease of using the oil produced in the plant with minimal processing. However, the environmental cost (land and water requirements) of growing these species will often not compete with many other species with much greater potential for biomass production. Application of appropriate selection criteria should focus attention on species with good potential for sustainable production. Following are some general criteria  for use high suitability for genetic improvementhigh biomass accumulationhigh harvest indexhigh fraction of biofuel in harvested biomassnutrients partition to nonharvested partsbeing able to be grown on marginal landsharvested material able to be stored in the fieldhigh bulk densityhigh water use efficiencyhigh N use efficiencylow potential as a weedhigh coproduct potentialoptimal biomass compositionlarge-scale potential productionlow cost of harvestBoth algae and seed plants are actively being investigated as potential energy crops. The growth of higher plants is a well-established process, and the risks and likely outcomes of research in this area are more predictable. However, research aiming to develop technology to grow algae on a large scale is more uncertain but may produce a highly efficient energy production system. Analysis of specific plant families is a useful level for systematic analysis of options for plants and their current and potential uses. All plants in a family will not have the same utility, but they often share common biochemical features that make the family a useful level for analysis. Modern DNA analysis methods have greatly improved the rigour and utility of higher plant taxonomy. The variation in the composition of plants in relation to their utility can now be analysed against this taxonomy. For example, the distribution of the major components of plant biomass, the major structural and nonstructural carbohydrates in these families, deserves re-evaluation. A good example of how plant taxonomy and biochemical composition relate is found in the plant families reported to contain fructans (polymers of fructose that serve as reserve carbohydrates). Current DNA-based systematic analysis suggests many other related families that should be examined for the presence of fructans. The presence of nonstructural carbohydrates in the form of fructans has implications for food use and for energy production from these species. The type of structural carbohydrate  can also be very important in determining the utility for food, feed or energy. The monocotyledonous plant families in the commelinoid group (including the grasses and related families) have cell walls rich in arabinoxylans and mixed linkage β-glucans . These cMany plants have been developed as food crops, and this suggests that we may need to domesticate many species to produce the biomass required to replace oil. Plants adapted to a wide range of available production environments are needed. The grasses (Poaceae) represent a major option having been domesticated for food production; they will probably repay screening efforts aiming to discover potential bioenergy crops. Many more plant families are probably able to contribute to the development of woody bioenergy tree crops. Some limited new options for domestication of food plants could also be identified by systematic analysis.Plant biotechnology provides tools that may allow rapid development of domesticated genotypes with growth and composition characteristics optimized for energy production .


We use wavelet-type discrete transforms for signal analysis on strings of finite length.We apply these transforms for edge and hidden Markov process detection. We alsopresent new approaches for string matching and for measures of the diversity ofchaotic strings.


Improvements in the performance of a laboratory computer systemdo not necessarily require the replacement of major portions of thesystem and may not require the acquisition of any hardware at all.Major bottlenecks may exist in the ways that the operating systemmanages its resources and the algorithm used for timesharingdecisions. Moreover, significant throughput improvements may beattainable by switching to a faster storage device if substantial diskactivity is performed. In this study the fractions of time used foreach of the types of tasks a laboratory computer system performs aredefined and measured. Methods for reducing the time fractions ofthe various types of overhead are evaluated by doing before and afterstudies. The combined results of the three studies indicated that a50% improvement could be gained through system tuning andfaster storage without replacement of the computer itself


The peripheral blood lymphocyte count has been measured in 74 cases of histologically proven carcinoma of the gastrointestinal tract. The count has been correlated with the pathological stage of tumour spread and the patient's delayed hypersensitivity response to 2.4 dinitrochlorobenzene (DNCB). A statistically significant correlation was found between the peripheral blood lymphocyte count and the response to DNCB. There was linear association between the extent of spread of the tumours and the lymphocyte count. Those patients with low peripheral blood lymphocyte counts tended to have more advanced tumours and a poor response to DNCB. The possible causes of this lymphopenia are discussed.


Beilstein Journal of Organic Chemistry. The series now embeds the subject firmly as a special interest area of the journal. The first series in 2008 presented contributions representing a wide range of organic fluorine chemistry [It is a pleasure to be able to introduce this second Thematic Series on ‘organo-fluorine chemistry’ within the hemistry –10 and tThe introduction of fluorine remains an important specialism in organic chemistry for modulating the physical properties of molecules involved in programmes ranging from bioorganic chemistry to performance materials. Consequently fluorinated organics are of major commercial significance to the pharmaceuticals, agrochemicals, materials and polymer industries with the fluorine fine chemicals industry servicing these industrial sectors. New innovations and insights into the synthesis and the nature and behaviour of organo-fluorine compounds continue to intrigue and this Thematic Series offers a glimpse into the level of activity in the area.I am delighted that all of the authors have agreed to submit such high quality contributions to render this Thematic Series substantial and make it such a success.David O'HaganSt. Andrews, April 2010


Peter Stastny and Peter Lehmann's Alternatives beyond Psychiatry offers a comprehensive and up to date account of the alternatives to mainstream psychiatry that are being developed by service consumers and survivors across the world. As psychiatry moves into a new age less dominated by a biomedical paradigm many of the approaches described in this book may be adopted by mainstream health services. This is a hugely readable and accessible book for professionals and consumers alike. Paul Hammersley is the Programme Director for Post Graduate Studies in cognitive behavioural therapy for psychosis at Manchester University's COPE Initiative in The United Kingdom. He is also an active therapist specialising in CBT for individuals experiencing severe psychological problems following traumatic life events. He has been widely published and has lectured extensively. 2006 along with Professor Marius Romme from Holland and The UK Hearing Voices Network, he founded CASL (The Campaign for the Abolition of the Schizophrenia Label.)The author declares that they have no competing interests.


Critical to the effective implementation of high throughput methods of synthesis is the necessity for a significant supporting level of automation. There are a number of critical issues associated with the successful introduction, and supporting role, of automation of small molecule chemical synthesis. Clearly there are needs for automation to increase drug candidate synthesis throughput. Automation of repetitive and laborious tasks associated with the synthesis process can release skilled chemists to apply their talents to the more challenging investigational aspects of developing new synthetic protocols. This provides continuity in the compound supply pipeline and ensures an optimal use of the automated platform for compound production. The very high fidelity of performing repetitive processes that can be managed through automation also removes some of the limitations and errors associated with more fallible human operators. This can include very difficult tasks associated with tracking data, and general information and inventory management. Taken collectively, these attributes associated with automation can lead to greater efficiencies, throughputs and improved allocation of human resources with concomitant reductions in costs associated with current day and future drug discovery. In our library development/synthesis paradigm, we feel that automation support must be invoked early in the process and that this automation support must continue throughout the project.


Germinal centers (GC) are an essential part of the humoral immune response. They develop a clear structure during maturation: Centroblasts and centrocytes are separated into two zones, the dark and the light zone. The mechanisms leading to this specific morphology as well as the reason for zone-depletion during a later phase of the GC reaction have not clearly been revealed in experiment. We discuss and weigh possible mechanisms of dark and light zone development in the framework of two mathematical models. In a comparative approach we formulate constraints on typical lymphocyte velocities in GCs which are characteristic for the different proposed mechanisms.


The evolution of metastatic colorectal cancer in patients who have had surgical treatment for a primary lesion was studied in relation the progressive changes in the blood levels of carcinembryonic antigen (CEA), to gamma glutamyl transpeptidase (GGT) and routine liver function tests (LFTs). Involvement of the liver could ofter be reliably predicted many weeks in advance of clinical diagnosis while metastases to other sites were less likely to be detected early by this test. The association of the extent of disease with the patterns of biochemical changes is discussed with reference to several illustrative examples.


A study of granulocyte function in myeloblastic leukaemia is reported. Function was assessed by the ability of peripheral blood granulocytes to ingest and kill Candida albicans in bitro. Depressed cidal activity was observed in 11 patients with smouldering leukaemia and in 19 patients with acute myeloid leukaemia. Cidal activity was lowest in the untreated acute disease; this improved during cytoreduction therapy and was maintained when remission occurred. Leukaemic plasma depressed the function of control granulocytes; the possible role of a plasma "factor" is discussed.


A fluorescence imaging system (Xillix LIFE – Lung Fluorescence Endoscopy system) usingfluorescence for the accurate diagnosis and early detection of lesions through an endosocopehas been developed. This system has applied an optical diagnostic technology to functionallydiagnose lesions which have been difficult to morphologically recognize or are occult withconventional endoscope. The benefit of this system in the diagnosis of lung cancer has alreadybeen confirmed in the US and Japan, and feasibility of the system in the gastric intestinal fieldhas also been evaluated.


The expression of thymidine kinase--an enzyme of the DNA precursor pathway--is strictly regulated during the normal cellular cycle, but is much higher and permanently expressed in malignant growing cells. We used this fact to detect neoplastic cells in samples freshly taken from leukaemia patients and kept frozen in liquid nitrogen until analysis. Using a new cytofluorometric assay for thymidine kinase in single cells, we were able to identify leukaemic cells in a surplus of normal ones. Our results demonstrate the benefits of this assay for leukaemia diagnosis.


Emerging infectious diseases and the growth of information technology have produced new demands and possibilities for disease surveillance and response. Increasing numbers of outbreak reports must be assessed rapidly so that control efforts can be initiated and unsubstantiated reports can be identified to protect countries from unnecessary economic damage. The World Health Organization has set up a process for timely outbreak verification to convert large amounts of data into accurate information for suitable action. We describe the context and processes of outbreak verification and information dissemination.


One hundred and ninety-one adults with acute myelogenous leukaemia were treated with combination chemotherapy consisting of daunorubicin and cytosine arabinoside (Barts III). Sixty-three patients achieved remission and were admitted to one of 3 trials of active immunotherapy: immunotherapy alone, immunotherapy and maintenance chemotherapy or neither of these. All patients had weekly clinical and blood examination and monthly marrow examination. Reinduction chemotherapy was given as soon as relapse was diagnosed in the marrow. The most striking observation was that immunotherapy was associated with easy and repeated reinduction of remission and marked prolongation of survival after first relapse when compared with immunotherapy plus chemotherapy. The possible reasons for this and the value of immunotherapy are discussed in relation to the third trial still in progress which includes 2 maintenance arms, immunotherapy alone and surveillance only.


Background: Impairments in oral word production are common at the onset of stroke. The identification of factors that predict early recovery has important implications for identifying those at greater risk of continued impaired functioning, and the management of the patient's care following discharge.Aims: To identify patterns of performance that are predictors of acute recovery of oral word production abilities following stroke;to identify any association between early and more chronic recovery.Method and procedures:Acute stroke patients were administered oral word production tasks within 1–2 days of hospitaladmission, with repeat testing by 7 days; a subset of patients had repeat testing between three weeks to one year later. Performancewas examined for error rate and type to identify potential predictors of early recovery.Outcome and results: The proportion of circumlocution and no response errors at initial testing were associated with the magnitudeof recovery of language functioning within the first week following stroke. Patient characteristics of age and gender were foundto have no influence on the degree of early recovery observed. None of the examined factors predicted late recovery. The degreeof early recovery was not associated with the degree of later recovery.Conclusions: The current study identified patterns of task performance that increase our understanding of how oral wordproduction recovers following acute stroke. The finding that the degree of early recovery does not predict the degree of laterrecovery is consistent with the hypothesis that early and late recovery are due to different mechanisms .


Epidemiological studies of active smokers have shown that the duration of smoking has a much greater effect on lung cancer risk than the amount smoked. This observation suggests that passive smoking might be much more harmful than would be predicted from measures of the level of exposure alone, as it is often of very long duration frequently beginning in early childhood. In this paper we have investigated this using a multistage model with five stages. The model is shown to provide an excellent fit to data on the incidence of lung cancer among smokers, ex-smokers and non-smokers in a cohort of male British doctors. Contrary to our expectation the model predicted only a slight increase in relative risk with increasing duration of passive exposure. Allowing for exposures early in life does not therefore explain the discrepancy between the relative risk of about 1.5 calculated from epidemiological studies of lung cancer and the low levels of exposure indicated by cotinine measurements in those passively exposed.


In order to assess the importance of the intensity of administration of chemotherapy in the management of advanced germ cell tumours we have calculated indices of chemotherapy. These have been used to compare the treatment given to patients who subsequently relapsed with matched controls who did not relapse. Two of these indices  are derived from the doses of drugs whose dose is varied . These indices showed significant variation between cases and controls. Indices gamma and delta are derived from drugs whose dose is not varied. They showed no significant differences between the two groups. These results emphasise the importance of ensuring that patients with these curable cancers receive adequate doses of chemotherapy.


Orthopedics had become a separate specialty within whole field of medicine about 50 years ago.The demands of the orthopedist have increased tremendously during the last 30 years because of changes in the demographic profile of population, increase in life expectancy, rapid urbanization and increasing speed of mobility. In developed countries the burden of orthopedic disease is because of aging population and social emphasis on the welfare of elderly. In low income countries it is because of increasing population, rapid urbanization and using high speed vehicles with poor road safety and driving standards. The abysmal health and living standards continue propagation of infective conditions. The increased life expectancy has added aging population.The advances in medicine have largely been empirical. The intuition has guided development through trial and error. Science has explained what was observed by clinicians.2Most of the orthopedic surgeons repair deficiencies in musculoskeletal system by established surgical methods2Orthopedic practices till now were guided by the research conducted in the West since the disease profile was more or less the same. In the present times the disparity between disease profiles has widened. The affluent nations have better living standards and health infrastructure. As a result the infective diseases are practically eliminated and degenerative problems are in plenty. Most of the research direction and funding is towards their needs while the low income countries which have 2/3 of world population still see the natural history of disease. They see the continued pathogenesis of osteoarticular infection.The research includes a clinical research and basic science research. Not many clinical problems can be solved by clinical research alone.We must resolve that basic and clinical research are two sides of one coin; both inseparable. Both require similar commitment and both must be integrated in the same clinical setting. Basic research is largely being conducted by nonphysicians world wide with a gradual decline in orthopedic surgeons as researchers. Basic scientists bring skill to the research proposal but find it difficult to appreciate the clinical relevance. Sarmiento believed, and rightly so, that an orthopedic surgeon who is trained as a clinician-scientist and who understands the capabilities and limitations of the basic science approaches is a superior collaborator.The number of clinician scientists has taken a steep decline in the last 30 years in America and Europe in spite of the state of art research facilities and adequate funding.On the contrary, low income countries have not yet started thinking about region specific basic research. They have very little infrastructure for research. The attitude of health planners is to support patient care. The education and research is left to the interest of orthopedic clinicians. Hence all research in these countries is conducted by clinicians because of their love towards research. The end result is that there is a very little contribution from these countries to the pool of knowledge. Even society does not recognize the researchers, while clinicians are recognized well. The low income countries should devote resources and part of health budget towards need based research. This has to be realized by teachers, orthopedic associations (whether of countries or region) and government health planners.Training programs on research methodology should be arranged. We should equip young clinicians with the skills to understand and appreciate the musculoskeletal biology and perhaps conduct serious research on locally relevant issues.7Low income countries have high income countries as an example. The progress in the field of research in orthopedics, the obstacles faced and solutions suggested by them are available. We should ensure credible research programs keeping all these lacunae and matching limited research facilities and heavy disease burden in mind. We should attract the best students in orthopedics for research by providing a structured research curriculum, appropriate funding and reward good outcome and support financial loss which they occurred by not practicing orthopedic surgery.8Indian Journal of Orthopaedics is making a step in this direction. We have three invited write ups in the Perspectives section from well established clinician-scientists from USA, South Africa and India to give their opinion on the (a) need and scope of basic research (b) prospects of basic research in their countries and (c) infrastructure needed for basic research. This is an attempt to sensitize the orthopedic community and Government in this direction.


Recent reviews of the management of hilar biliary cancer suggest that radical resection is the preferredtreatment option. It seems true that most of the long term survivors are treated this way, but it is equallytrue that most patients receive palliative rather than curative treatment. Before we go too far in ouradvocacy of radical treatment, we need to develop methods for quantifying palliation because that is intruth what we usually achieve. A method of quantifying palliation is described. Surgeons are encouragedto use methods of this kind in order to allow valid comparison of the results of different methods oftreatment.


It has been reported that decreased numbers of dendritic cells (DCs) are correlated with poor prognosis in some types of malignancy, such as gastric cancer. However, factors that determine the density of DCs have not been characterized. It was recently reported that vascular endothelial growth factor (VEGF) inhibits the functional maturation of DCs from CD34+ precursors. In this study, we analysed the relationship between the expression of VEGF and the density of DCs in gastric carcinoma tissues by immunohistochemical staining. The extent of infiltration by DCs was graded from marked to slight on the basis of the mean densities of DCs. The prognosis of patients with marked infiltration was significantly better than that of patients with slight infiltration among patients who had undergone curative resection. Multivariate analysis showed that infiltration by DCs was an independent prognostic indicator. Furthermore, there was an inverse correlation between the density of DCs and the expression of VEGF Our results suggest that expression of VEGF might be associated with tumour progression and poor prognosis not only because VEGF stimulates angiogenesis, but also because it allows tumours to escape from attack by the immune system in patients with gastric carcinoma.


The elevated levels of ras-related cellular RNA in a series of colorectal carcinomata (n = 12) was correlated with conventional staging criteria (tumour morphology and Dukes' staging) and with clinical outcome with particular reference to the development of metastatic disease. No direct relationship was evident between these parameters suggesting that although abnormal expression of ras oncogenes may be critical in the development of malignancy, variations in the level of their expression do not appear to be directly related to clinically evident phenotypic differences.


Metastases to axillary lymph nodes is an important factor in predicting prognosis and survival in primary operable carcinoma of the breast. A series of post mastectomy lymph nodes (150 cases) was selected in this retrospective study, in which the initial diagnosis had been no metastases by light microscopy and in which a long follow-up was available (average 10 years). The original H&E sections from these cases were immunostained to detect metastases which might not have been previously appreciated. The study was performed using a cocktail of 5 monoclonal antibodies directed against epithelial antigens. The object was to explore the possibility of detection of occult micrometastases by immunohistochemistry and to evaluate their prognostic significance. Micrometastases with individual cells and cell clusters were readily detected by this technique in 14% of all cases. It also became apparent towards the end of the study that micrometastases could be detected with equal sensitivity by any one of the 5 monoclonal antibodies. Positive staining of malignant cells was found to be more frequent in invasive lobular carcinoma (ILC) than in invasive ductal carcinoma (IDC). However, for the IDC group a striking association was found between micrometastases and both recurrence and survival rate. The ILC sample was considered too small for meaningful interpretation. We recommend the use of immunohistochemical techniques using monoclonal antibodies for the detection of occult metastases in lymph nodes to improve the prediction of recurrence and survival in invasive ductal carcinoma of the breast.


EHP 116:1071–1076; Akre et al.][.Hypospadias is a male birth defect in which the opening of the urethra is located on the underside of the penis instead of the tip. Although the defect is common and increasing in prevalence , the causes of most cases are unknown. Some studies suggest that reduced levels of the placental hormone human chorionic gonadotropin (hCG) may play a role; others suggest associations between hypospadias and conditions such as low birth weight, preterm birth, and preeclampsia that could be caused by malfunction of the placenta and subsequent abnormalities in hormone regulation and nutrition provided to the fetus . A new study now presents additional evidence that hypospadias has its origins in malfunction of the placenta Data on 292 cases of hypospadias and 427 controls were collected as part of a joint Danish–Swedish study of both hypospadias and cryptorchidism (undescended testes). In Sweden, hypospadias cases were recruited at a pediatric surgery clinic, and data were collected via self-administered questionnaires. In Denmark, cases were from the Danish National Birth Cohort, a population-based cohort of women and children. Mothers were interviewed while pregnant and twice after delivery. Matched controls were born within at least 6 months of each case and within the same county, and were randomly selected from national birth and population registries.The investigators found several conditions independently associated with increased hypospadias risk, most of which they say could be explained by impaired production of hormones by the placenta. Mothers without first-trimester nausea were twice as likely to bear sons with hypospadias, as were mothers who had a prepregnancy body mass index of 30 or greater. These findings support the theory that placental insufficiency contributes to hypospadias. Nausea is believed to be caused by an early surge of pregnancy hormones, and the absence of first-trimester nausea is associated with low hCG levels. A previous study showed that obese women have lower levels of a family of proteins called plasminogen activator inhibitors, some of which are derived from the placenta.The team also determined that a maternal diet lacking both fish and meat was associated with more than a fourfold increased risk of hypospadias in baby boys. This finding complements a 2000 study by other authors that showed a strong positive association between maternal vegetarian diet and hypospadias in offspring. The authors of the current study conclude that exclusion of animal proteins could increase the risk of a transient deficiency of some nutrient that’s essential for formation of the organs or the placenta. Another explanation is that some protein sources in vegetarians’ diets (such as soybeans) contain compounds with hormonal effects that may affect the development of the urogenital organs in humans.


Therapeutic response in patients with advanced breast cancer is conventionally assessed with reference to criteria devised by the International Union Against Cancer. Evidence to date suggests, however, that assessments of equivalent quality may be obtained at lower cost from the use of serum markers. The paper presents estimates of potential cost savings resulting from the use of serum markers in place of conventional assessment and argues that the size of these savings merits the establishment of a randomised controlled trial.


The cellular content of receptors for epidermal growth factor (EGF) was measured in different histological subgroups of human mammary carcinomas. EGF receptors were detected in 36% of the ductal and all the medullary carcinomas. In contrast lobular and pure colloid tumours did not contain measurable amounts of the receptor. The receptor was found both among tumours with an euploid and aneuploid DNA pattern. The EGF receptor is thus found in carcinomas with a varying degree of differentiation as judged by the cellular DNA pattern. There was no correlation between the proliferative activity of the tumours as measured by thymidinekinase activity and the amount of EGF receptors in the tumour. Tumours with detectable EGF receptor often had low levels of oestrogen receptor. This finding could only partly be explained by the menstrual status of the patients.


Electron spin resonance studies have been made of caeruloplasmin and iron transferrin levels in whole blood of healthy controls and patients with a variety of malignant conditions receiving various forms of treatment. A small difference was found in caeruloplasmin level between normal males and females, although normal females receiving contraceptive steroids had an elevated level. No difference was found in iron transferrin level. Various conditions increased the caeruloplasmin and some also decreased the iron transferrin level in patients with malignant disease. These included surgery and the approach of a terminal phase of disease. Once allowance for these factors was made, the remaining small differences in Cu and Fe between patients with either squamous cell carcinoma or breast cancer and controls appeared to have no clinical significance.


Thymectomy effectively prevents the development of spontaneous lymphoma in the AKR but how this effect is achieved remains to be determined. One possible mechanism, namely suppression of genomic expression of the oncogenic murine leukaemia virus now seems unlikely since levels of the group specific MuLV antigen were in comparision with their sham operated controls unaltered in both neonatally and adult thymectomized AKR.


The important paradigm shift for asthma care that focuses on clinical control has revolutionized the understanding of the disease and its optimal pharmacological care. UnfortunThe February 2010 new release from the U. S. Food and Drug Administration (FDA) requires new safety measures and warnings for the use of inhaled long-acting beta agonists (LABAs) in asthma control .[2] SuchCertainly, this new FDA safety release on the use of LABAs will create some confusion among asthma care workers, patients and related drug companies. However, the bright side of such warnings is that it will for sure reinforce the tendency of asthma care workers to revisit the stepwise (whether up or down) approach of pharmacotherapy recommended by most recent national and international asthma guidelines.–6 The maSome of these FDA warnings for LABA inhalers can be considered as fine-tuning and reinforcement of the already comparable recommendations stated in most recent asthma guidelines.–6The use of LABAs as monotherapy and as a reliever medication is strongly discouraged because of potential health hazards.LABAs may be used in combination with ICs in the stepping up of treatment for the long-term management of only such asthma that is uncontrolled by controller medications.Patients should be maintained on an asthma controller medication once asthma control is achieved.A combination product of ICs and LABAs should be used only to ensure compliance with both medications.Surprisingly, among these FDA warnings, the new recommendations are to shorten the period of use of LABAs even if in combination with ICs and to discontinue its use, if possible, once asthma control is achieved. These new advices are somewhat welcome as true phenomena of stepping-down in the treatment of well-controlled asthma.These recommendations might open the gate for the use of other alternative controller agents that can optimize asthma control. They have also stressed the implementation of non-pharmacological measures for achieving the control of asthma. These include the identification and avoidance of triggering and exacerbating factors  to minimize the overall use of any unnecessary pharmacological agents in order to avoid their potential future hazards for health. These meFurthermore, I would also like to take these warnings to share a personal view about similar safety requirements that may be needed for the solo use of short-acting beta agonists (SABAs), which is recommended in asthma guidelines as reliever inhalers.–6 Such cIn conclusion, this new FDA safety release on the warnings for the use of inhaled LABAs is very well saluted. It will motivate the asthma care workers to revisit the stepwise pharmacotherapy approach recommended by most current asthma guidelines. It recommends the use of LABAs to be limited to the combination with ICs for cases with uncontrolled asthma and to be administered for the shortest possible duration. The solo use of LABAs might soon become history in the management of asthma. Extension of similar cautions for solo use of SABAs is a personal vision that will be challenged further by benefit/ risk profile in future clinical investigations.


Dear Editor,et al.[I read with interest the brief report by Parija et al. and apprThe clinical presentation was suggestive of raised intracranial pressure, with the diagnostic workup pointing to cerebral venous thrombosis (CVT). CVT is a relatively common presentation of polycythemia vera. When we This report highlights the diagnosis of an uncommon hematological condition which primarily presented to an ophthalmologist. CVT is often under diagnosed even by neurologists. It should be remembered that almost 40% of CVT patients present with signs and symptoms suggestive of isolated intracranial.4 A thoroVisual loss in CVT maybe due to thrombotic ischemia of any structure of the visual pathway or due to pressure on the optic nerve due to the transmitted raised intracranial pressure (ICP). All cases of CVT with visual loss require visual field analysis and measurement of optic nerve sheath diameter using B-scan ultrasonography (USG). Visual loss in patients with CVT due to transmitted raised ICP (indicated by increased optic nerve sheath diameter on USG) not amenable to medical management is an indication for optic nerve sheath decompression (ONSD). ONSD as a treatment option for the visual loss in the left eye should have been offered to the patient in this case, as it has been shown to be effective even in the presence of optic disc pallor.5 Moreove


Many marine coastal ecosystems are threatened by increasing waste discharge, and bioassays are needed because chemical and physical tests alone are not sufficient to assess potential effects on aquatic biota. In light of the fact that larval metamorphosis of benthic invertebrates is usually very sensitive to environmental changes, this paper reviews sensitivity comparisons of larval metamorphosis with other common bioassays in different species and those in different developmental stages of the same species, and it discusses the potential use of larval metamorphosis as an indicator of marine environmental quality.


An analysis of past and present Australian legislation for managing and regulating contaminated sites confirms that such legislation must deal with a number of specific matters.Australian legislation is effective in some of these areas but poor in relation to others. The analysis will assist other countries and jurisdictions to create effective legislation more speedily by avoiding identified problems.


The American College of Surgeon’s Coalition for Quality in Geriatric Surgery will formally launch a national initiative aimed to improve the quality of surgical care for all older adults in July 2019. The first-year goal will be to recruit and successfully verify 100+ medical centers. This presentation will provide an overview of dissemination efforts for the standards set for providing high quality surgical care for older adults as well as processes to measure the quality of care provided to older adults at these medical centers. It our vision that this national initiative will lead the effort to the improvement of surgical care of all older adults.


There are errors in the Funding statement. The correct Funding statement is as follows: The current study is funded by Iran National Science Foundation with grant ID 940007 and 95824986 to Sima Rafati. Also Farnaz Zahedifard received funding from Pasteur Institute of Iran as part of her Ph.D studentship. She also got Calmette and Yersin training scholarship from RIIP foundation from Institut Pasteur International Network for her training period in South Korea. The founders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.


The authors noticed that the cartoons in Both the HTML and PDF versions of the article have been corrected. These errors appear only in print and PDF versions downloaded on or before August 21, 2018.


Alzheimer’s disease (AD) and temporal lobe epilepsy (TLE) are the most common forms of neurodegenerative disorders characterized by the loss of cells and progressive irreversible alteration of cognitive functions, such as attention and memory. AD may be an important cause of epilepsy in the elderly. Early diagnosis of diseases is very important for their successful treatment. Many efforts have been done for defining new biomarkers of these diseases. Significant advances have been made in the searching of some AD and TLE reliable biomarkers, including cerebrospinal fluid and plasma measurements and glucose positron emission tomography. However, there is a great need for the biomarkers that would reflect changes of brain activity within few milliseconds to obtain information about cognitive disturbances. Successful early detection of AD and TLE requires specific biomarkers capable of distinguishing individuals with the progressing disease from ones with other pathologies that affect cognition. In this article, we review recent evidence suggesting that magnetoencephalographic recordings and coherent analysis coupled with behavioral evaluation can be a promising approach to an early detection of AD and TLE.Highlights–Data reviewed include the results of clinical and experimental studies.–Theta and gamma rhythms are disturbed in epilepsy and AD.–Common and different behavioral and oscillatory features of pathologies are compared.–Coherent analysis can be useful for an early diagnostics of diseases. It is known that theta and gamma oscillations are closely related to cognitive processes. The theta rhythm (4–12 Hz) is prominent oscillations recorded in the hippocampus and surrounding limbic structures during exploration and REM sleep  or “nested” oscillations  evoked a firing of hippocampal neurons, which reflects an integrated representation of spatial and temporal information  during the performance of cognitive tasks  complex of rats and guinea pigs revealed that normally theta oscillations were relatively synchronous in these brain regions  compared to healthy control was revealed , an impairment of cross-frequency gamma amplitude modulation by hippocampal theta rhythm was observed  suggests that these diseases have some common properties and, probably, at least partially similar mechanisms of their development.The potential relation between TLE and AD has been supported by experimental and clinical data. Thus, aging is a common and well-established risk factor for epilepsy and AD (Armon et al., Many clinical evidence indicates an increased comorbidity of seizure pathology in AD: it is becoming clear that AD is associated with neuronal hyperexcitability as well as network hypersynchronicity, which is the main reasons of epilepsy development (Eichler and Meier, At the same time, neurodegenerative processes peculiar to dementia can play a central role in the development of epilepsy in the patients predisposed to cognitive deficit. Adult-onset epilepsy of unknown cause could thus represent a risk factor for the ongoing neurodegenerative damage, even when epileptic manifestations and clinically recognized dementia are separated by long time (Cretin et al., The facts of cognitive impairment in animals with epileptiform activity were derived from different studies devoted to the role of the tau peptide (Roberson et al., In the hippocampus, one of the main foci of cell death in TLE and AD brains, the network hypersynchronicity and epileptiform activity can be the result of formation of extensive aberrant neuronal connections. This aberrant remodeling was revealed in epileptic rats and in APP transgenic mice (Harris et al., It is known that the main problem in diagnosis of neurodegenerative diseases is the detection of neuronal abnormalities at early stages of their development. At present significant achievements have been made in the development of methods for the detection of some biomarkers of AD and TLE, including cerebrospinal fluid and plasma measurements and glucose positron emission tomography (Shiihara et al., At present, the methods for detection of theta–gamma coherence during cognitive loading are still not absolutely perfect. Thus, changes in theta–gamma coupling may simply reflect memory-related increases in gamma power and phase synchrony (Montgomery and Buzsáki, The author confirms being the sole contributor of this work and approved it for publication.The author declares 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 population of persons aging with disabilities is growing. Being able to segment aging with disability sub-populations within national data sets is becoming increasingly important in order to understand the relationship of aging with disability to a range of outcomes in later life including health and wellness, economic security, and health and long-term service and support need and use. This symposium includes four examples of how existing data can be used to draw conclusions about the experience of old age for persons with intellectual or developmental disabilities. In addition, the symposium offers insights into the limitations of these data and the presentations lend themselves to a discussion of how measurement across disability sub-population can be ope rationalized. Two of the presentations focus on understanding mortality trends of adults with cerebral palsy and down syndrome--including an understanding of the health conditions facing these populations. A third presentation will focus on cardiovascular risk factors and co morbidity among adults with cerebral palsy. Finally, a fourth presentation will focus on pairing qualitative understanding with quantitative trends to offer a deeper understanding of the health management challenges for adults with disability as they age. Through a deeper understanding of the experience of health in later life for adults with disability, ideas about interventions and supports can be better aligned with the needs of these populations.


The exact neurophysiological mechanisms of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) for treating patients diagnosed with depression are still not clear. Results of previous structural and functional MRI studies showed an aberated functional connectivity in major depressive disorder (MDD)  which induces very mild sensations in the skin  stems from obsolete medical point of view that the stimulating electrodes do not enter the crania . The real effect of “non-invasive” electromagnetic stimulation (rTMS and tDCS) cannot be measured directly due to their non-invasive nature. Opitz stated in recent research, that the important point is in interpretability of stimulation effects  can decrease the complexity of electrophysiological signal (Čukić et al., Several researchers who used various non-linear measures of complexity of EEG confirmed that physiological complexity is elevated in MDD (Ahmadlou et al., Bestmann et al.  demonstrAlthough it can seem impossible to compare the two non-invasive brain stimulation techniques that are so different in the sense of their electromagnetic properties and the level of power they can induce in the living tissue, we can still recognize the same functional pattern. In many review papers exploring the efficiency of both rTMS and tDCS in clinical applications (Brunoni et al., For all electromagnetic stimulation treatments, the effect is of temporary nature. The rationale is that they can at least ameliorate the symptoms for a limited time; after which they need to be repeated. The common advantage of non-invasive brain stimulation techniques over medications is that there are no foreseeable harmful side-effects (Antal et al., Although study of physiological complexity changes is still in the realm of research and mainly not in use in clinical setting, it is expected that soon clinicians would start using varying electromagnetic modalities of stimulation with better understanding of how they work—as means to decrease complexity characteristic of depression. Further research based on empirical data is necessary before making the final conclusion that non-invasive brain stimulation treatments may work through changing physiological complexity.To conclude, after all above mentioned results of various lines of research that tried to bring us closer to understanding various aberrations of depression, both rTMS and tDCS might be efficient because of their ability to decrease characteristically elevated levels of physiological complexity in depression.MČ conceived the idea about the article, performed a literature research and wrote entire text.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


We offer a novel perspective on the burgeoning literature focused on loneliness later life by examining the language(s) used to describe, define and depict loneliness. We have an extensive body of work describing the prevalence of , ‘vulnerability factors’ and consequences of loneliness in later life. These activities start with pre-defined concepts of what loneliness is and often use scales and questions which may/may not use the term loneliness. How well does the contemporary language of loneliness used in research, policy, practice and the media really capture the depth and complexity of what people are experiencing? Do the terms and words use in our measurement scales and quantitative research resonate with this vocabulary? In qualitative research interviews how do older adults talk  about loneliness? How does the media talk about loneliness and what images does this convey about later life? We will address these three issues in our seminar. Using data from qualitative interviews undertaken as part of a mixed methods study of temporal variations in loneliness, Thomas uncovers the strategies participants used to talk or avoid talking about loneliness. Victor uses qualitative data from 12,000 adults aged 60+ collected as part of the BBC loneliness experiment to examine the terms used to describe loneliness and to identify both the opposite of loneliness and the positive aspects of loneliness. Sullivan exposes how loneliness is constructed in print and digital media over a 10-year period in the UK and Canada and its role in framing the loneliness problem.


Resilience has been examined in various age groups, initially focused on vulnerable children and more recently in enhancement of resilience in various age groups and in response to trauma. Based on studies of resilience in Holocaust survivors and intergenerational engagement to promote resilience in former gang members and isolated older adults, Corley’s 3E model of Experience, Expression and Engagement is discussed in terms of multiple studies and the implications for forming and strengthening networks in communities at risk. This includes initiating creative coalition-building endeavors to address loneliness in residential settings for older adults evolving from a project funded to the Motion Picture and Television Fund in Los Angeles from the AARP Foundation.


The global prevalence of sensorineural hearing impairment was first reported by the World Health Organization (WHO) in 1985.–At the individual level, the burden of hearing loss over the life course is substantial and can be exacerbated by negative societal attitudes and prejudice towards affected people. In general, hearing loss has adverse consequences on interpersonal communication, psychosocial well-being, quality of life and economic independence.,,The main drivers for the rising trend in hearing loss include demographic changes attributable to global population growth and improved life expectancy.,,,Since 2007, WHO has promoted increased public awareness of hearing loss through World Hearing Day, held every March. Actions required to curtail the growing number of people with hearing loss and to improve quality of life for those with hearing loss have also been extensively reported.The sustainable development goals explicitly recognize the need for a better quality of life and opportunities for optimal well-being throughout the life course of all people with disability.


Sound and movement are perceived through the vibration of modified ciliary bundles located on the apical surfaces of specialized mechanosensory hair cells. These hair cells derive from specific regions of the otocyst that become determined to develop initially as sensory epithelia and ultimately as either hair cells or supporting cells. The number of hair cells in an individual vertebrate is surprisingly small and the ability to replace these cells varies among different classes. The molecular and cellular factors that specify hair cell identity are not known, but the results of recent experiments have begun to identify some of the signaling pathways that play important roles in hair cell development. This review will describe recent findings related to the factors that influence the final choice of a progenitor cell to develop as a hair cell and discuss their implications for the overall development of the auditory and vestibular systems.


Concerns have been raised that the transplants performed in the local context at the time of procedures reported in this article  may haveThis article  reports PLOS ONE Editors retract this article.International ethics standards call for transparency in organ donor and transplantation programs and clear informed consent procedures including considerations to ensure that donors are not subject to coercion. Owing to the lack of documentation to demonstrate this study had prospective ethical approval, insufficient reporting, concerns about the use of prisoners as transplant donors, and unresolved concerns around the informed consent procedure used for organ donors, and in compliance with international ethical standards for organ/tissue donation and transplantation, the The first author notified the journal that all authors agree with the retraction. The other authors either could not be reached or did not respond directly.


Recent findings from longitudinal followup studies of adolescents and adults with fetal alcohol syndrome (FAS) indicate that the deficits associated with this disorder are long lasting and pervasive. In addition, followup data from several large, prospective studies of cohorts representing a broad range of alcohol exposure levels have confirmed that although FAS represents the severe end of a continuum of birth defects, moderateAccumulating evidence shows that many FAS deficits can be detected at infancy and remain through adolescence into adulthood. In particular, an abnormally small head circumference  and intellectual problems persist as an affected child matures, whereas behavioral, emotional, and social problems can become more pronounced e.g., . In addiIn a recent long-term followup study of a Seattle cohort of adolescents and adults with FAS, This article aims to demonstrate the need to differentiate the impact of prenatal drinking from the impact of the environment in which the child is raised when assessing neurobehavioral and other outcomes in children whose mothers drank both during and after pregnancy. In the 20 years since FAS was first identified, a major body of research has been compiled on the effects of prenatal alcohol exposure as well as the impact of being raised by an alcoholicAn association between drinking during pregnancy and neurobehavioral function in infants and children normally is interpreted as teratogenic . The specific body systems affected by alcohol exposure and the resultant outcomes depend on when exposure occurs during the prolonged period of CNS sensitivity to alcohol see . For exaOne alternative explanation—that an observed deficit is attributable to the socioenvironmental consequences of being raised by a drinking mother—can be evaluated by examining the relationship of the deficit to postnatal maternal alcohol use. In cases where the mother drinks both during and after pregnancy, however, it may not always be possible to determine the degree to which observed deficits are attributable to teratogenic versus socioenvironmental factors. Statistical analyses that include variables related to both prenatal and postnatal drinking behavior may sometimes obscure true prenatal effects and result in the failure to recognize a true effect or in an understatement of the magnitude of the effect .Two analytical approaches have been used to assess the impact of prenatal versus postnatal drinking on the child. One approach was used in a prospective longitudinal study  conducte(1) the Fagan Test of Infant Intelligence , (2) a tAs seen in A second analytical approach for assessing the effects of drinking during and after pregnancy was used in a longitudinal study conducted in Atlanta, Georgia . The defA similar pattern of results was seen when The data from these studies are consistent with findings demonstrating that cognitive performance is less affected by alcohol exposure in infants and children whose mothers stop drinking in early pregnancy, despite the mothers’ resumption of alcohol use after giving birth e.g., . Thus, tThe impact of being raised by an alcoholic parent has been examined extensively in the research on children of alcoholics (COA’s), but few studies have compared the effects of being raised by an alcoholic father versus an alcoholic mother. Most COA research has focused on children whose fathers have problems with alcohol abuse or alcoholism, but whose mothers do not, in order to exclude the effects of alcohol exposure attributable to maternal drinking during pregnancy. Little is known about the impact of these nonalcoholic mothers’ drinking habits on their children. As previously noted, however, recent findings  have detThe studies cited in this article illustrate the need to distinguish the effects of drinking during pregnancy from the consequences of being raised by a drinking parent. The methods described here reflect some of the advances in this research area that have enabled investigators to better distinguish between the harmful effects of prenatal alcohol exposure and the additional impairment that may be incurred in an environment in which one or both parents drink heavily. Current research is beginning to explore complex models and is attempting to identify specific factors  that may buffer or increase the magnitude of the damage incurred by alcohol exposure.


Radiographers have been providing their opinion on radiographic findings to referring physicians in Australia in an informal capacity for some time. Evidence has shown improved outcomes for patients when radiographers and referring clinicians work collaboratively as part of a multidisciplinary healthcare industry.A number of barriers have been identified to the implementation of formalised radiographer abnormality detection systems in Australia which include the following: lack of education, lack of confidence and lack of support from radiologist colleagues.In recent times, Logan Hospital in Queensland has set the standard for radiographers to fulfil full scope of practice with the implementation of a formalised PIE system. The prospective longitudinal study by Brown et al.


This finding highlights how junior doctors, whether in a formal training programme or not, are particularly vulnerable to the adverse effects of a patient suicide, with potential effects on recruitment and retainment in psychiatry.2 The projects involve annual events to promote knowledge and discussion about quality and safety; discussions about the process of serious incident investigations and the support available at each junior doctor induction; and the development of a written resource on formal and informal sources of support for junior doctors involved in a serious incident investigation. These projects are under constant review in order to respond to trainee feedback.In our mental health trust in South East London, trainee-led initiatives in collaboration with the postgraduate training department have been making changes to the learning and support offered to junior doctors who are involved in a serious incident investigation in the past 5 years.We thank the authors for the valuable work exploring how suicide can affect doctors of any grade. We hope that mental health trusts and postgraduate training departments continue working to develop formal and informal support structures for doctors experiencing this difficult event.


Concerns have been raised that the transplants performed in the local context at the time of procedures reported in this article  may haveDetails as to the donor sources and methods of obtaining informed consent from donors were not reported in this article , and wheThe authors state that no vulnerable populations were involved in their research and all organs were obtained voluntarily but did not provide ethics approval documentation or consent forms to support their claim or clarify whether organs had been procured from prisoners.The authors did not respond to inquiries about the availability of underlying data supporting this study.PLOS ONE Editors retract this article.Owing to the lack of documentation to demonstrate this study had prospective ethical approval, insufficient reporting, unresolved concerns around the source of transplanted organs and whether they included organs from prisoners, and in compliance with international ethical standards for organ/tissue donation and transplantation, the The corresponding author notified the journal that all authors disagree with the retraction. The other authors either could not be reached or did not respond directly.


This paper presents the process by which we adapted an existing Alzheimer’s Disease and Related Dementia (ADRD) caregiver support intervention that is directed at multiple family caregivers and culturally-responsive to the needs of the Arab American community. Three focus group discussions with Arab American families caring for a family member with ADRD were organized in partnership with the Arab Community Center for Economic and Social Services (ACCESS). Focus group discussions included two members from each family to gather data on needs of Arab American ADRD caregivers, role of family in caregiving and use of technology for caregiving information. Results underscored the lack of and desire for knowledge around ADRD, and the perception by Arab Americans that they differ from non-Arab Americans in approaches to caregiving . These data confirm the need for caregiving interventions responsive to Arab American needs/preferences.


Evidence is mounting that patient-reported experience can provide a valuable indicator of the quality of healthcare services. However, little is known about the relationship between the experiences of people with severe mental illness and the quality of care they receive. We conducted a study to examine the relationship between patient-reported experience and the quality of care provided to people with schizophrenia.We calculated a composite global rating of quality of care for people with schizophrenia using data from an audit of 64 mental health providers. We then examined associations between these ratings and mean patient satisfaction and patient-rated outcome using data from a survey of 5608 schizophrenic patients treated in these services.r = 0.33; p = 0.01) but not with patient satisfaction . Patient-rated outcome was also positively correlated with patient involvement  and the quality of prescribing practice . High patient satisfaction scores were significantly associated with the extent of use of care plans within each organisation .Global rating of quality of care was positively correlated with patient-rated outcome (Among people with schizophrenia, patient-rated outcome provides a better guide to the quality of care than patient-rated satisfaction. Greater use of patient-reported outcome measures should be made when assessing the quality of care provided to people with psychosis. Improving the quality of care that patients receive is a key objective for healthcare providers across the world. As well as safety and clinical effectiveness, patients experience of care is a key component of most definitions of quality of healthcare .In recent years evidence has begun to emerge that patient-reported experience can offer a reliable indicator of the quality of care that services provide –4. A sysSmall scale studies have examined the relationship between patient-reported experience and other measures of quality of care. For instance, Shipley and colleagues  investigThe second round of the National Audit of Schizophrenia conducted between 2013 and 2014 assessed the quality of care provided to patients with schizophrenia across all the Mental Health Trusts in England and Health Boards in Wales. As the audit provided data on a wide range of outcomes of care for patients with schizophrenia around the county, we set out to use data from this audit to examine whether patient-reported experience provides an indication of the services’ overall quality of care in a nationwide cohort of patients with severe mental health illness.The National Audit of Schizophrenia provided an in-depth examination of service performance against 16 standards of care derived from national guidelines for the treatment of people with schizophrenia in England . These sA total of 64 NHS Mental Health Trusts in England and Health Boards in Wales (referred to collectively as ‘Trusts’ in the remainder of this report) participated in the audit. Data were collected via an audit of practice tool and a contemporaneous patient survey. The audit of practice tool was developed specifically to measure standards of care and the relevant data were obtained from the patients’ case records .The quality of patient involvement (e.g. whether there was shared decision making process in the selection of medication).Compliance with recommended prescribing practice (e.g. extent of polypharmacy and prescribing above BNF recommended maxima).Access and uptake of evidence-based psychological treatments.Provision of a care plan jointly developed with the patients to meet their needs.For each Trust, we calculated the proportion of patients for whom each individual standard was met and the mean percentage of compliance for each standard relative to the total national sample. We then calculated a global trust rating score based on the mean percentage of compliance of each Trust across all standards assessed with the audit of practice tool. We also calculated five sub-scores from standards relating to:The patient-reported experience measures we used included a measure of patient satisfaction with care and a patient-rated outcome measure. The question on patient satisfaction with care asked: “Taking everything into consideration, are you pleased with the care you have received from the service so far?” Responders had to indicate their answer by using a four-points Likert scale from 1  to 4 (very satisfied). The question on patient-rated outcome asked: “To what extent have services helped you to achieve good mental health in the last year?” and patients responded using a four-point Likert scale ranging from 1 (made me worse) to 4 (helped a lot). We calculated the mean trust scores for these two questions and converted them into a 100-point scale.We carried out Pearson product-moment correlations to investigate associations between patient satisfaction and patient-rated outcome scores with the global trust performance and subgroups of care scores .The National Audit of Schizophrenia (NAS) was commissioned by the Healthcare Quality Improvement Partnership (HQIP) as part of the National Clinical Audit Programme (NCA). As part of NCA, all Mental Health Trusts in England and Wales were expected to take part in NAS. Consent was not required from the patients to publish the audit data in the audit’s main report or for research purposes and the data were collected by the audit team in such a manner that the patients could not be directly identified.The audit team received 5733 returns from the audit of practice, of which 5608 were used in the analysis after data cleaning with a mean of 88 SD = 17) returns per Trust. In total, 3379 patients submitted a survey form with a mean of 53 (SD = 19) per Trust and a response rate of 26.4%. Table 7 returnsp < 0.01). In Table There was a positive significant correlation between the patient satisfaction and the patient-rated outcome measure (rs = 0.582, The results relating to the five subgroups of patient care we examined are also presented in Table Secondary analysis of data from this national audit of care for people with schizophrenia found that patient-rated outcome was positively associated with an independent rating of the global quality of care provided by these services. In contrast, we did not find an association between global quality of care and the patients’ satisfaction with the service they received. High scores on patient-rated outcome were also correlated with high patient involvement in the decisions about their care and with high compliance of the services with the recommended prescribing practice. In contrast, high levels of patient satisfaction were associated only with the provision of a care plan tailored to the patients’ needs. Nonetheless the strength of these associations are not strong and caution needs to be exercised in interpreting the results of this analysis.While the previous work of Doyle and colleagues  demonstrThe main strength of this study is that we were able to examine the relationship between patient experience and quality of care across a large number of providers of mental health services throughout England and Wales. However, the study also has a number of limitations which need to be considered when interpreting the results. Firstly, the audit used two different samples for collecting case note data and for the patient survey, which did not allow us to determine whether individual patient ratings related to the quality of care provided to them personally by their Trust. The use of aggregate data from different samples of patients within each Trust may have underestimated the strength of the associations we might have seen, had both sets of data come from the same patient sample.A second limitation of the study was that the measures of patient-rate experience and the global trust rating we used have not been validated. The global rating of trust quality of care was developed from standards for the treatment and management of people with schizophrenia published by the National Institute for Health and Clinical Excellence following a systematic review of published literature and extensive consultation with patients and providers . HoweverWhile we found a moderate degree of association between patient satisfaction and patient-reported outcome in our analysis, only the latter was correlated with the independent rating of global quality of care provided Trusts. This suggests that patient-rated outcomes might be a better indicator of the quality of care that a service provides than patient-rated satisfaction with care. We also found that the two measures of patient-rated experience were associated with different elements of care delivered by participating Trusts. The more the services promoted the patients’ involvement in decisions about care and higher levels of compliance with recommended prescribing practice were associated with patients being more likely to state that services were improving their mental health. On the other hand, services that had higher compliance with recommendations that patients should have a care plan that was jointly developed to meet their needs had higher ratings on patient satisfaction with care.These results support previous research in other healthcare settings which indicate that patients rate their experience and outcomes of care according to different criteria and highlight the importance of both in assessing the overall quality of care that healthcare services provide , 12.In recent years concerns have been expressed about the burden that providers of healthcare services face in assuring the quality of care they deliver , 14. TheIn summary our findings highlight that, feedback from patients with severe mental disorders can provide important information about the quality of care they receive. Therefore, greater use of patient-reported experience measures should be made when assessing the quality of care provided to people with psychosis. Future work should focus on exploring the best way to combine patient views with audit data to obtain a comprehensive picture of the quality of care that services provide.


The fruits of this collective endeavour include an understanding of the genetic architecture of the disease, an appreciation of its complex pathophysiology, and much progress in clinical management. However, many challenges remain, particularly with respect to disease prevention and the management of progressive heart failure.The first description of hypertrophic cardiomyopathy (HCM) can be attributed to any number of great anatomists and physicians working from the 17th century onwards, but the modern era is often said to have begun with Donald Teare’s landmark paper of 1958HCM differs in several important aspects from other conditions associated with left ventricular failure and cardiac hypertrophy. From a clinical perspective it has a well-known association with sudden cardiac death but it also represents an important prototype for diastolic heart failure. The natural history of heart failure in HCM is notably longer than that of ischaemic heart disease with symptom evolution and remodelling occurring over decades. In about one third of patients the presence of intra-cavity or left ventricular outflow tract obstruction provides an additional haemodynamic burden and endothelial and microvascular dysfunction are present from an early stage and contribute to the genesis of symptoms and disease progression. The prognosis of HCM is also highly variable with sudden death the major cause of mortality in younger patients and heart failure and stroke the major causes of death in older individuals. Earlier diagnosis within families has also led to a growing number of healthy carriers of pathogenic mutations that offer opportunities for early intervention to prevent disease.Global Cardiology Science and Practice, we present a unique series of papers that review the aetiology, clinical presentation and management of HCM from childhood to old age. The series reveals how the simple notion of HCM as a disease defined by hypertrophy unexplained by loading conditions, encompasses a remarkably complex spectrum of genetic and acquired disorders. Sudden death prevention with implantable cardioverter defibrillators and the management of left ventricular outflow tract obstruction are comprehensively reviewed, but attention is also given to the management of rare but important phenocopies. The nuances of management in particular sub-phenotypes are also discussed and illustrate the need for systematic and expert evaluation of this and other complex heart muscle disorders.In this special issue of For many decades, the diagnosis and management of HCM has run in parallel with technological developments that permit more precise and timely diagnosis but not necessarily greater insight into pathogenesis or novel therapies. In 2018, however, there are signs that a new and exciting chapter in the story of HCM and other cardiomyopathies has begun with the transition of molecular genetics into the clinic and a growing number of randomised clinical trials designed to ameliorate and perhaps even prevent disease. It is our sincere hope that this expert series will spur readers to learn more about this fascinating group of diseases and to contribute to this landscape of therapeutic opportunity.


Enigmatically, mitochondrial disease can affect individuals at any age and in any tissue (Lightowlers er et al  use mous To assemble much of the chain of enzyme complexes that perform oxidative phosphorylation (OXPHOS) requires coordinated expression and assembly of gene products from both the nuclear and the mitochondrial genome. The catalogue of diseases associated with mitochondrial dysfunction continues to increase, and in many cases, the ubiquity of exome or whole genome sequencing has enabled the identification of the genetic mutations responsible for these pathogenic defects  occurred early on, whilst the axonal and locomotor degeneration only developed later, and were not the consequence of generalised brain atrophy. The tandem knockout of both YME1L and OMA1 restored the dynamic mitochondrial network, but despite this restoration of L‐OPA1, not only did the combination of eye defects persist but both the neuroinflammation and axonal degeneration became more severe, with an earlier onset. The combination of models used in these investigations brings us a little closer to understanding pathogenic mechanisms and that disruption of mitochondrial proteostasis alone can be a driver for disease.What is the relationship between this change in mitochondrial morphology, eye defects and axonal degeneration with age? Sprenger The authors declare that they have no conflict of interest.


Akkermansia muciniphila and Anaerotruncus colihominis are swapped. A revised There is an error in As stated in the Competing Interests statement on the original article, all authors have patents pending in relation to this work. The following sentences are added to the Competing Interests statement as an additional clarification: The healthy reference ranges reported in this article were used in the development of a commercially available test product developed and marketed by uBiome. This does not alter our adherence to PLOS ONE policies on sharing data and materials.


This symposium presents early results on epigenetic, transcriptomic and other aging biomarkers such as telomere length and mitochondrial DNA copy number from the Health and Retirement Study that allows a detailed examination of the biological pathways through which socioeconomic conditions influence the human aging process. In 2016 HRS collected 6 tubes of blood from people who completed the 2016 interview, had been in the sample at the prior wave and were not in a nursing home  to maintain a nationally-representative sample. These blood samples were analyzed for novel biomarkers of aging that included global methylation arrays, whole transcriptome sequencing, telomere length and mitochondrial DNA copy number among other biomarkers that were shown to be related to both social and economic circumstances and health outcomes at older ages. This level of integration of biological data to address social disparities hasn’t been accomplished before on a large nationally-representative sample of Americans and will provide a unique opportunity to understand the biological mechanisms through which social disparities affect human health. The symposium will describe the utility of measuring novel age related biomarkers in a nationally representative population study such as HRS and the potential research opportunities that can be pursued using this publicly available resource. It will provide an overview of the measurement and distribution of epigenetic, transcriptomic and telomere length and mitochondrial DNA copy number as novel aging biomarkers. It will also describe the utility of these biomarkers in further understanding the biological underpinnings of socioeconomic differences in health and mortality.