There is a growing amount of literature to support the view that active involvement in research by consumers, especially informed and networked consumers, benefits the quality and direction of research itself, the research process and, most importantly, people affected by cancer. Our exploratory project focuses on identifying their priorities and developing a process to assess the research needs of Australian cancer consumers which may be useful beyond the cancer scenario.This project was consumer initiated, developed and implemented, with the assistance of a leading Australian cancer consumer advocacy group, Cancer Voices NSW (CVN). Such direct involvement is unusual and ensures that the priorities identified, and the process itself, are not influenced by other interests, regardless how well-intentioned they may be. The processes established, and data collection via a workshop, followed by a questionnaire to confirm and prioritise findings, and comparison with a similar UK exercise, are detailed in this paper.Needs across five topic areas reflecting cancer control domains  were identified. Cancer consumers high priority research needs were found to be: earlier diagnosis of metastatic cancers; the extent of use of best practice palliative care guidelines; identifying barriers to cancer risk behaviour change; and environmental, nutrition and lifestyle risk factors for people with cancer. A process for identifying consumers’ research priorities was developed and applied; this may be useful for further investigation in this under-studied area.The findings provide a model for developing a consumer derived research agenda in Australia which can be used to inform the strategic direction of cancer research. Consumers have been seeking a workable method to achieve this and have worked in collaboration with a major cancer charity, which funds research, to do so. Research is central to improving health and contributing to overall national development. Australia has made substantial investments in building and enhancing its health research capacity in recent years. Despite these efforts and some notable examples of success,2, the oNo public research funding program can afford to service all potential health research questions, each program must identify priority areas and questions. Within Internationally, there is an increasing call for public involvement in identifying health research priorities including distinguishing where and why resources should be allocated. GreaterThere is currently a limited understanding of the research needs of people affected by cancer in Australia. Moreover, published projects that specifically determine needs and gaps are few-21. TherA previous UK study found thThis project set out to investigate the views of those affected by cancer in New South Wales, Australia on what they consider should be the key priorities for future research in this area. The purpose of the paper is to provide information on the research needs of NSW cancer consumers and describe the priority setting process so that interested parties may duplicate the approaches used. The findings, key issues and challenges in the identification and utilisation of consumer research needs are discussed.This exploratory project adopted a participatory approach, where project ownership was shared with people affected by cancer. Cancer Council NSW (CCNSW), a leading non-government cancer charity and research funder, partnered with Cancer Voices NSW to design and implement an approach to capture cancer consumers’ research needs. CVN, as a peak Australian cancer consumer group with members from all areas of the state of New South Wales had identified this work as a pressing need. Ethical approval was received from the CCNSW Ethics Committee.Constantly communicating with members is a critical, ongoing aspect of the work of CVN. The organisation routinely surveys its members to ensure an up-to-date understanding of the perceptions and experiences of cancer consumers and to support decisions that will best help people affected by cancer. CVN uses knowledge acquisition to support member empowerment and information, and inform broader policy and advocacy processes.Cancer consumers, including those impacted by the disease directly, or indirectly as friends or family members, were invited to participate through the following channels: (1) CCNSW website and constituent mail-outs, (2) CVN’ s newsletter and networks, (3) cancer support group contacts and cancer care centres, and (4) via a range of cancer charities and consumer groups. The opportunity was also advertised in the volunteer section of a large, well known recruitment website.Global Cafe’ approach, which had been recommended by CVN, was the main data collection method selected in this part of the project. The Global Café process is a technique for harnessing group experience and views on a number of topics, and channelling this output into a usable data set[The methods used to capture consumer research needs were developed after careful deliberation of the support, funding and timeframe within which we were required to work. A workshop designed broadly on the ‘data set.Data collected from CVN’s own bi-annual survey on cancer research needs was included with an invitation to all participants. They were also asked to provide written input from their constituencies which was incorporated within the pre-workshop data to provide a robust list of consumer research needs.Prior to and at the commencement of the workshop, participants were provided with information to clarify their general understanding of cancer research across the cancer control spectrum from cancer prevention to screening, diagnosis, management, survival and end of life care. This was designed to focus thinking about cancer research and lead to more informed discussions of what should be researched. Each of these five topic areas became the individual focus of table discussions in the workshop. Participants at each table were asked to discuss the topic as a group, giving their rationale for research interests and then record those research topics they felt to be important on ‘post-it’ notes.Ideas and conversations of no more than eight participants at each table were linked and built upon as people moved to different tables, cross-pollinating ideas for each topic area and identifying research needs that mattered to their own lived experiences and/or those collected by their consumer network or group. The living network of conversations evolved through several rounds of exploration and research question identification until all participants had the opportunity to input into each of the five topic areas. A cancer researcher or CCNSW research program staff member acted as an advisor on each table for participants’ questions, and if participants required information on research currently being undertaken in the area. The advisors brought discussions back to the issue of research needs if discussions began to go ‘off track’. A pre-selected consumer table host remained at each table and briefed new table arrivals on previous discussions to ensure each new group built on the topic in an iterative exchange process. The needs identified through the small group process were then fed back by the consumer host to the whole group and discussed. This enabled an effective summary of the discussion and also permitted any additional views not covered in the small group to be raised.To verify the workshop results and achieve higher quality results CVN canvassed their membership of over 300 consumers who had been affected by cancer or were interested in cancer control via a general postal questionnaire. A few had attended the workshop. The questionnaire, planned and developed by SC and CS, and tested for readability and ease of understanding by another member of CVN, invited personal reflection on the research needs of consumers. Included with the questionnaire was an explanation of the workshop process and results to ensure an understanding among members of the context within which the questionnaire was sent. CVN members were asked whether their needs reflected some or all of those identified in the workshop. Members were also asked to rate their research needs from 1 to 5, with 1 being their highest research priority. They were asked to identify 5 priorities in each section.Members were asked to send their responses back to CVN in the included stamped, return addressed envelope. Details of the process steps employed in the project are provided below.Steps in the consumer research needs and priorities identification process1. The requirement for cancer consumer involvement in identifying research needs is established by consumers and acknowledged by professional partners who commit resources and coordination support to the process.2. A project reference group is established to support the design and implementation of the consumer research needs identification process.3. Consumer research needs identification approach is clarified and agreed by all parties.4. Participant recruitment is planned and carried out.5. Global Café workshop process is developed in detail by the project reference group.6. The information needed for the workshop is identified and assembled, such as on the cancer control research domains, to help inform participants’ discussions during the workshop and help them build on existing knowledge during their exchanges.7. Pre-workshop input from members of each consumer group represented at the workshop and the results of previous Cancer Voices NSW survey results are collected for incorporation with the data and information obtained in the workshop.8. Workshop conducted as planned using the Global Café process.9. The research needs of cancer consumers are confirmed at the end of the workshop. Follow-up via an emailed report of the workshop outcomes is undertaken to ensure that the final research needs truly reflect the views and advice expressed during the workshop.10. Workshop findings are strengthened via CVN postal questionnaire to members.11. The final identified priority issues are compared with a similar project to support the generalisability of the results and help ensure that the priorities are not just intrinsic to this project’s particular process or participants12. A final report is disseminated to consumer groups, research funding and research organisationsPost-it note entries, which were automatically categorised within each of the five cancer control research areas discussed by the workshop table groups, were examined. Repeating issues were identified and summarised. An independent assessment of all data by two members of the project team (CS and SC) was undertaken to ensure consistency in the interpretation of the data.Member priorities were analysed using SPSS version 16 for Windows and are Thirty two people with direct experience of cancer across different cancer types responded to the invitation to participate in the workshop. This number was accepted as workable for the purpose and the process. Participants ranged in age from 18 to 72 years. More females (n=18) than males (n= 14) attended the workshop. Consumers identified needs across the five cancer control research domains with cancer treatment drawing the greatest number of identified issues. Needs across the domains  ranged from a better understanding of unhealthy behaviours such as smoking and sun exposure, to researching factors related to differences in cancer outcome due to personal and geographical inequity, and better understanding the cancer control needs of vulnerable groups such as older people, culturally and linguistically diverse and indigenous people. Improvements in health systems and professional capacity to better meet the needs of the population and quality of life issues for cancer patients, carers and significant others were also deemed to be important areas for inquiry.An overview of the identified needs within the cancer research domains from which they were raised are provided below.Prevention and risk• How can media improve understanding (and behaviour change) of cancer risk factors linked to personal behaviours, with attention to confused use of relative and absolute risk messages?• Definitive research into nutrition and other lifestyle risk factors and cancer development• What are the barriers to cancer risk behaviour change and how can positive behaviour change be encouraged?• What is the need in Australia for a rare cancer registry to increase volume of and ease of access to information about these cancers?• What are the perceptions of cancer in culturally and linguistically diverse (CALD) communities?• How can barriers to prevention be removed and cancer awareness raised amongst CALD groups?• How can young people be better supported to understand cancer risk?• Further research into cancer clusters• Further research into environmental risk factors for cancer development• What are the most effective interventions for dispelling myths and misconceptions about the causes of cancer in our community?• Impact of technology on cancer risk – eg mobile phones, CT scans, etc.• Degree of impact of multi risks in causing cancers• Do prevention messages cause unnecessary feelings of guilt and self blame?What is best use of public health dollars re cancer prevention?Screening and diagnosis• How can behaviour be changed to improve cancer screening rates?• What steps are needed to increase skin cancer screening?• What are the most effective channels for consumers to access information about cancer?+ age group• What is the cancer screening benefit for 70• What is the scale of exposure to diethylstilbestrol in the Australian communityWhat are the perceptions and barriers to cancer screening among different cultural groups?• What interventions work best to increase cancer screening in different cultural groups?• What interventions work best to increase cancer screening in indigenous groups?• What are the best approaches to meet the cancer information needs of different groups?• Investigate genetic testing services in Australia to determine and compare service effectiveness across different population groups and localities• What is the role and capacity of the general practitioner in encouraging patients to undertake cancer screening?Is general practitioner training to detect early signs and symptoms of cancer adequate?• What constitutes a supportive workplace when cancer is diagnosed?• How can metastatic cancers be diagnosed earlier, preferably before symptomatic?Treatment• More investigation into targeted therapies and personalised medicine for all cancers• Which cancers will benefit from development of immunotherapy?• Identify best practice treatment protocols and guidelines for all rare cancers• Overview of research relating to patient treatment profiling for all cancers• Which drugs available overseas but not to Australians should be fast tracked?Determine which advanced cancers have yet to have treatment guidelines and address• Are elderly Australians offered adequate cancer treatment & management?• What is the difference in cancer treatment decisions of those living in rural, regional and remote areas?• What are the preferred treatment choices of CALD and Indigenous groups in Australia compared with best practice management?• Is access to best practice cancer treatment determined by cost in Australia? What impact does this have on health outcomes?• Investigate the extent and causes for the under representation of particular groups in cancer clinical trials i.e. older people, rural, minorities etc.• What are the levels of access to cancer clinical trials for residents of rural Australia?• Is there equity in cancer treatment throughout Australia?• How can people living in rural areas be best supported emotionally and financially to receive best practice cancer management?• How can elderly cancer patients be best supported in self management?• What are the best approaches that health care providers can use to prevent or alleviate patient guilt at cancer diagnosis?• How can medical care providers be best trained to deliver a cancer diagnosis that is aligned with the patient and family’s level of understanding, emotional and support needs?• How effective is the communication between different the medical specialists for those with cancer and unrelated co-morbid conditions?• To what extent are general practitioners ‘kept in multidisciplinary care loop’ of cancer patients?• What value does multidisciplinary care provide cancer patients?• What is the currency of cancer specialist and General Practitioner evidenced based knowledge?• What is the current and predicted need for additional geriatric oncologists in Australia?• More clinical trials investigating the effectiveness of complementary therapies in cancer control• How can greater awareness of clinical trials in patients and clinicians be better supported?• How user friendly and accessible is cancer patient prescription drug information?• How can we maximise knowledge transfer among researchers working on different cancer types and research disciplines?• What are the training needs of personal carers of cancer patients and the current availability of such training?• What are the variations in response to pain management?• Identify more effective pain management for cancer patients• Identify individualised pain management interventions• How can chemotherapy be made less toxic?• How can the side effects of treatment be better managed?• What are the different needs of men caring for women with cancer; and women caring for men with cancer?• What is the extent of carers of cancer patients who are socially isolated and what are their service and support needs?• What is the extent of carers of cancer patients who are depressed and what are their service and support needs?• Survivorship• How can the long term effects of chemotherapy be best addressed?• What are the particular needs and wants of people living with cancer who do not have adequate social capital?• What is the level of fear of cancer recurrence among survivors?• How can the normalisation process be supported ?• What are the long term effects of repeat diagnostic or prognostic scans for cancer survivors?• More studies on the effects of chemotherapy on long term cognition• What is the extent (and intervention availability) of male and female fertility issues post cancer treatment?• What are the best approaches that can be used to establish and sustain cancer support groups in rural areas?• Is cancer survivorship related to a greater chance of personal relationship breakdown?• How can children caring for adults with cancer be best supported?• What information to survivors need and who should provide it?End of life care• What is the extent of use of best practice palliative care guidelines – for patients, carers and family? Gaps?• What are cancer patients' attitudes to dying with dignity and control?• Is access to good information about end of life issues , adequate?• What are the most effective interventions to ensure palliative care service availability in rural and remote areas?• What is the acceptability and impact of a professional support person in improving the experience and outcomes of those with advanced cancer?• What extent do different social environments impact on end of life care?• What are the long term affects and counselling and support needs of carers after the death of a loved one?• What is it that people value about dying at home? What is it they fear about dying elsewhere?• What are the needs and areas of unmet needs for respite care for patients and families?• What is the impact of differing views about end of life, of patient and carer, if any?how can metastatic cancers be diagnosed earlier before they are symptomatic?’ as their greatest research need. The second highest priority research questions (32%) were found to be ‘what is the extent of use of best practice palliative care guidelines?’ and ‘more research into nutrition and lifestyle risk factors for people with cancer’ Other high priority research areas include identifying the barriers to cancer risk behaviour change and research into environmental risk factors.Fifty seven (19%) of CVN members completed and returned the questionnaires. The majority of respondents were female (56%) aged between 61–70 years (41%). The large majority of respondents reported that the research needs identified at the forum reflected either all or some of their needs (98%) with almost 60% stating they reflected all their research needs. One third of members (33%) identified the research question ‘The most common research priorities across all respondents’ first to fifth selections were:‘How can the long term effects of chemotherapy be best addressed?’ (selected in the top five priorities of 77% of respondents)• ‘How can behaviour be changed to improve cancer screening rates?’ (selected in the top 5 priorities of 75% of respondents) and• ‘How can the normalisation process be supported ?’ (selected in the top 5 priorities of 68% of respondents).• This exploratory project facilitated identification of cancer consumers' priority research needs over five topic areas reflecting major cancer control domains. These were found to be earlier diagnosis of metastatic cancers; the extent of use of best practice palliative care guidelines; identifying barriers to cancer risk behaviour change; and environmental and nutrition and lifestyle risk factors for people with cancer. A process for identifying consumers’ research priorities was developed and applied; this may be useful for further investigation in this under-researched area.The findings of this project should not be considered in isolation. Consumer research priorities are neither better than nor a replacement for priorities identified by health researchers. They are made available via this project and a range of other published investigations to support researchers to both understand prevailing consumer concerns and needs, and to support and inform decisions on what to research. Ideally consumers and researchers should always work together to identify and detail research topics.The paucity of Australian research in this area necessitated the use of a broad exploratory approach. The main limitation is the generalisability of findings for a larger population of cancer consumers. However asking consumer organisation representatives to collect the research needs of constituents prior to the workshop is likely to have reduced this problem, as is the comparison of findings of this project with those of a much larger UK study. The similarity between our results and the UK study results suggests that our results are comparable to other populations of cancer patients.A further limitation is the low response rate (19%) to the postal questionnaire. However, we believe that this low number can be explained in part by the belief among numerous CVN members that they had already provided input on the topic in previous forums. We therefore believe that the views of non-responders are not substantially different from responders.The findings of this project provide the basis for developing a consumer derived cancer research agenda in Australia, and can be used to help inform the strategic direction of cancer research over the longer term. They also provide direction for cancer care, education and information funding. Australia does not have adequate channels through which community members can express their research priorities or through which they can receive information about the broad scope and success of research being made in the fields with which they are concerned. Lack of recognised processes and resources to collect and analyse relevant information from consumers represents an important obstacle to context and culturally sensitive research needs identification in Australia. At the same time, societal expectations of health and medical research are growing.Global Café method is a user-friendly approach for generating meaningful and cooperative discussion within and between different groups.The study sought to harvest diverse input from cancer consumers on the issues they need addressed through research. Identifying research needs can be challenging. What processes should be used to determine needs? How can this be done in a systematic, ongoing and efficient manner? What timelines for action should be assigned? This paper adds to the small range of available successful approaches that can be used to capture the research priorities of those directly affected. The It has been argued that consumers do not have adequate understanding to identify useful research priorities. This maDecision makers in publicly funded research systems are under growing pressure to improve priority setting processes and to be more accountable for research funding decisions. There is currently no established structure or mechanism in Australian public research funding schemes that allows consumer research needs to be incorporated. Researchers require training to understand and appreciate what is happening in health and health care overall, and with those adversely affected by too few research answers. Long term partnerships with the end recipients of research provides experiential and contextual learning that are the key to ensuring research is of benefit to and is valued by society. Liaising with intellectual colleagues and attending scientific seminars and conferences alone are unlikely to provide insight into the experiences of those with health problems. Researchers need to be inspired by the individuals and families of those in need of the benefits of focussed research.Earlier diagnosis of metastatic cancers; an understanding of the extent of use of best practice palliative care guidelines; identifying barriers to cancer risk behaviour change; and environmental and nutrition and lifestyle risk factors for people with cancer, were found to be the most pressing needs of cancer consumers on the subject of cancer research. The findings of this study offer a workable process for identifying the research needs of health consumers and may be applicable to scenarios other than cancer.In an era where research is making important progress in our understanding of disease causation and avoidance, and identifying real and potential cures, hopes are pinned on every piece of research to drive more progress. Today’s more informed society is eager and able to encourage a purposeful research culture and direction. Hence, we see the need to build and maintain a critical mass of researchers who are competent in partnering with consumer groups, which in turn can offer capable consumer representatives. This partnership will lead to joint needs identification and priority setting, and to performing quality research of societal relevance.Neither author has any competing interests to report.Both authors contributed to the design of the project. CS undertook the review of the literature, facilitated the workshop, undertook data analysis and was the main author of the manuscript. Representing Cancer Voices NSW, SC brought this consumer initiative to the CCNSW for possible implementation. SC was a working member of the key reference group, assisted in facilitation of the workshop, organised the postal questionnaire, undertook data analysis and contributed to the preparation and editing of the manuscript. Both authors have read and approved the final manuscript.


Over the past several years there has been growing interest in the high prevalence of vitamin D deficiency in both the general population and among people living with HIV infection. Vitamin D deficiency in the setting of HIV infection is likely multi-factorial with contributions from environmental factors as well as possible associations with HIV therapy. This lecture will highlight recent data on the prevalence and possible consequences of vitamin D deficiency in the setting of HIV with a focus on the relationship between vitamin D deficiency and HIV disease progression and possible metabolic and inflammatory consequences of chronic vitamin D deficiency. Finally, the talk will attempt to shine a light on areas for further investigation.


Uterine fibroids are the most common gynaecological tumours found in women. These tumours are said to be present in 80% of Caucasian women and are even more common in women of African origin. In 50% of women with fibroids symptoms usually occur, leading to complications from the presence of these fibroids. Although they are mainly a problem in the reproductive years, there are reports of problems from fibroids in postmenopausal women.The management of patients with fibroids is quite variable including conservative oral and parenteral treatment, conservative and radical surgery, and newer techniques such as uterine artery embolisation and radiofrequency ablation. All of these techniques can also cause complications for the patient, and as a result careful evaluation of patients must be done to decide on the correct treatment option for a particular patient.The focus of this special issue is to highlight the complications which are caused by fibroids and also those which can arise as a result of the treatment options available. This is intended to assist clinicians and their patients in making informed decisions about the management of this common problem. The journal is the effort of a truly international group of clinicians giving varied experiences from across the world.Complications of uterine fibroids and their management” is from Jamaica and outlines the entire spectrum of complications of fibroids and their treatment. This is a good review of the modern methods available and should be helpful to clinicians to assist them in counseling their patients.The paper entitled “Innovative oral therapy for uterine leiomyomas” is a collaborative effort of clinicians from Egypt and the United States of America (USA) reviewing the use of oral therapy for the treatment of fibroids. This paper gives an update on the modern use of drugs to treat fibroids to avoid surgery.The paper entitled “Surgical management of uterine fibroids at Aminu Kano Teaching Hospital” is from Nigeria, and this paper discusses use of myomectomy versus abdominal hysterectomy in their setting. The authors have outlined their experience and given the reader an idea of their methodology and complication rates comparing the two procedures.The paper entitled “Intrauterine adhesions following conservative treatment of uterine fibroids” is from Sweden and Spain discussing the complication of intrauterine adhesions reminding readers how to diagnose and treat this often forgotten complication of surgical treatment of fibroids.The paper entitled “Indications and outcomes of uterine artery embolization in patients with uterine leiomyomas” is from Japan, and the paper entitled “Complications associated with uterine artery embolisation for fibroids” is from the United Kingdom. Both papers discuss their experience with uterine artery embolisation. The complications from both sites are outlined.The paper entitled “Radiofrequency ablation for treatment of symptomatic uterine fibroids” is from the United States and the United Kingdom and reviews the use of radiofrequency ablation to treat fibroids. This is an excellent review detailing older now archaic methods and outlining the more modern safer techniques used in their setting.The paper entitled “Overall this journal is an excellent resource for physicians who wish to review uterine fibroids as well as all the methods available to treat them. The complications of fibroids are outlined in detail, and the different treatment modalities and possible complications are also outlined. This should become a standard compendium on fibroids for students and physicians for the benefit of increasing knowledge for examinations as well as the proper counseling and management of patients.Horace FletcherHorace FletcherCelia BurrellCelia BurrellBharat BassawBharat BassawEarlando ThomasEarlando Thomas


The aims of the study were to examine: (1) the relationship between parental income and schooling and using Complementary and Alternative Medicine (CAM) for their children; (2) the relationship between giving the recommended vaccines and usage of CAM for children; and (3) the frequency and characteristics of CAM usage in children from different socio-economic layers.The study was done via a self-reporting anonymous questionnaire by parents of 535 children, in 5 primary care pediatric clinics located in different areas in Israel, representing a population from different socio-economic classes.Twenty-seven percent of the respondents reported that they used CAM for at least one child in their family. Parents with higher education and income used CAM more than less educated parents and those with lower incomes. Parents who have tried CAM for themselves used it also for their children. Parents who have not vaccinated or partially vaccinated their children used CAM more than parents who gave their children all of the recommended vaccines. Parents tend to attach importance to the pediatrician notification for using CAM.A significant portion of the population use CAM for children. CAM use in children was more frequent among families in a high socio-economic level. Most of the parents who used CAM for themselves did the same for their children, due to their positive experience and their desire to improve the health of their children using other methods outside of conventional medicine. Parents who tend not to vaccinate or partially vaccinate their children were more likely to use CAM, because this treatment is perceived as more “natural". The common use of CAM in children requires raising the awareness and knowledge of pediatricians to this phenomena and improving the communication between parents and pediatricians regarding CAM usage, for the benefit of the children.


Storing chemical structures and reactions in relational databases with the aid of database extension modules usually called cartridges is an industry standard. Typically such cartridges provide a fixed set of functions to facilitate structure queries , chemistry data file import and export, sometimes structure manipulations or standardizations, and occasionally a defined set of property computations. We extend this model by transplanting a complete scriptable chemical information processing toolkit into a database extension. With the aid of this tool a new realm of custom chemistry data operations and queries can be accessed directly in the database, and by means of SQL functions that can be used in any SQL statement. We discuss the design of the software and prototypical solutions this it can deliver.


Cerebral cortex is generally thought to provide the neural basis for higher cognitive and perceptual functions  and via an iPad or iPhone “app.” From the results, the authors were able to propose how particular groups of neural pathways centered around cerebral cortex might subserve specific cognitive functions. This article illustrates the importance of a comprehensive neuroanatomical assessment of a complete brain.A solution to this Neuroinformatics challenge is important for progressing the discovery of cortical wiring principles. In an ambitious study (Solari and Stoner, Overall, we think this Research Topic demonstrates the complexity and diversity of cortical organization and the wide variety of approaches that can and have been made to understand how we think and perceive. We hope the reader will find something here to stimulate their curiosity concerning a topic of considerable importance to the individual and society.


Idiopathic toe walking (ITW) is a condition that commonly presents to podiatrists. This presentation aims to give an overview of the quality of literature focused on the treatment of ITW and determine if common podiatric treatment modalities are evidence based. 24 articles reporting treatment modalities were appraised against the National Health and Medical Research Council Levels of Evidence. There currently is no evidence of any single treatment option having long term effect on ITW gait. The highest level of evidence was in support of serial casting or surgery with some evidence supporting the use of Botulism toxin Type A.Footwear and orthotic intervention with or without stretching programs are reported treatments with no rigorous studies to support these modalities yet anecdotally these are reported effective. This article aims update the knowledge of podiatrists, to enhance how children who present with this gait style can be managed and highlight areas for future research.


Strain of the myocardium is conventionally presented in the polar coordinate system since it adapts best to the morphology of the heart. Strain calculation would be facilitated considerably if the CMR tagging patterns were in the radial or circumferential direction. However, the CMR tagging is implemented mostly in the Cartesian coordinate system as it is prescribed by SPAMM technique in which the gradient fields create only parallel taglines. Radial tagging is not used widely due to SAR problem for tight radial pattern. Implementation of circular tagging, to the best of our knowledge, has not been reported yet. Here we introduce an approach that makes both patterns possible for tagging based on off-resonance excitation. Its theoretical basis and practical details as well as initial results in phantoms and human hearts are presented.A rotating excitation plane in combination with a continuous RF pulse results in substantial excitation on a patterned region using off-resonance effect. A spoiler gradient destroys the net transverse magnetization on the region and generates the tagging with the specified pattern. The actual implementation of these cine sequences was performed on a commercial imaging platform  by using developmental software .The developed sequences were tested on phantoms and applied on healthy volunteers Figure . Images New tagging sequences were theoretically described and actually implemented. The sequences have been successfully tested on phantom and also used to acquire short axis images of the left ventricle. The spatial resolution and density of taglines for the radial tagging are considerably higher compared to its previous schemes and allows for relatively simple derivation of myocardial shear rate and angular strain.


The recommendations are presented with supporting evidence level.In this report, guidelines for the evaluation, medical and surgical management of renal cell carcinoma is presented. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7 Renal cancer represents the third common genitourinary cancer in Saudi Arabia after urinary bladder and prostate. It accouAll cases of renal cell carcinoma should preferably be seen or discussed in a multidisciplinary forumth edition was usedThe American Joint Commission on Cancer Staging TNM 7The Memorial Sloan Kettering cancer center risk classification for metastatic disease will be used: Risk facEach of the above gives a score of one. Patients will be classified according to the total score as follows:


To the Editor: The recent article by Louie et al. underscores a more general disparity between the need for autopsies in potential infectious disease deaths and our present national capacity  that prevent pathologists from enthusiastically performing autopsies on those who died of potential infectious diseases, including prion diseases. One potential solution is the creation of regional centers of excellence for infectious disease autopsies that could operate in conjunction with a mobile containment autopsy facility ,6. Such


Drosophila has a primitive yet effective blood system with three types of haemocytes which function throughout different developmental stages and environmental stimuli. Haemocytes play essential roles in tissue modeling during embryogenesis and morphogenesis, and also in innate immunity. The open circulatory system of Drosophila makes haemocytes ideal signal mediators to cells and tissues in response to events such as infection and wounding. The application of recently developed and sophisticated genetic tools to the relatively simple genome of Drosophila has made the fly a popular system for modeling human tumorigensis and metastasis. Drosophila is now used for screening and investigation of genes implicated in human leukemia and also in modeling development of solid tumors. This second line of research offers promising opportunities to determine the seemingly conflicting roles of blood cells in tumor progression and invasion. This review provides an overview of the signaling pathways conserved in Drosophila during haematopoiesis, haemostasis, innate immunity, wound healing and inflammation. We also review the most recent progress in the use of Drosophila as a cancer research model with an emphasis on the roles haemocytes can play in various cancer models and in the links between inflammation and cancer. Drosophila has undoubtedly been a powerful model organism for the study of nearly all essential and fundamental biological processes. What we have learned from the fruit fly has expanded our knowledge in life science at an unprecedented speed. This is in particular due to the recent availability of the complete annotated genome, a versatile array of genomic modifying techniques and powerful life imaging tools. Cellular and molecular mechanisms underlying many basic biological processes have been discovered to be highly conserved between Drosophila and mammals. For example, the Notch, Hedgehog (Hg) and Wingless (Wnt) pathways first identified in Drosophila embryogenesis and the Runt and Hippo signaling pathways conserved in the Drosophila haematopoiesis and tissue growth are also implicated in the progression of various human cancers  and innate immunity with such precision that the time is now ripe for us to look into the active dialogs between these fundamental processes in the context of mammalian inflammation and cancer. Drosophila has a primitive open blood circulation system with only three types of blood cells or haemocytes circulating in the haemolymph during a fly's life span. The majority of the circulating haemocytes in the haemolymph are macrophage-like cells that engulf and degrade apoptotic cells and invading pathogens. Haemocytes perform vital roles through their contribution both to cellular and humoral immune responses in the fly. In combination with the currently well-developed Drosophila tumor models, the roles of haemocytes in tumor regression and/or progression can be explored and important clues can be obtained to understand further the inflammatory responses in relation to tumors; the focus can be directed more at the molecular and cellular level by use of sophisticated genetic manipulation and live imaging tools. Tian Xu and colleagues have done pioneering work in this direction by using a Drosophila tumor model to investigate the role of haemocytes in the tumor growth control during a systemic inflammatory response  direct killing by Antimicrobial peptide (AMP) released into haemolymph from rapid de novo synthesis in the haemocyte and fat body; (2) direct killing by Hydrogen Peroxide (H2O2) or Nitric Oxide (NO) agents produced during melanisation; and (3) immobilization of opportunistic pathogens by blood coagulation at an open wound  Dizzy was also identified to be required for the embryonic haemocyte migration  signaling which is also used by the mammalian neurophils in response to chemotaxic cues  Basket (Bsk) and Rac1. Bsk is also found to regulate the turnover of focal adhesions in the circulating haemocyte in the larva  investigated the integrin adhesion activation and maturation in the migration of the sessile haemocyte population in the late larval stage into pupal stage  and also stress/danger signals  into the nucleus. Dorsal and Dif are homologs of mammalian p50 and p65. Apart from these secreted cytokines, a cytoplasmic lysosomal protein called Psidin has been found to be the link between the haemocyte phagocytosis and AMP activation in the fat body in the larval immune response  is the enzyme required in melanisation to catalyze the oxidation of mono- and di-phenols to ortho-quinones, which polymerize into melanin. PPO in normal physical conditions is enzymatically inert. A serine protease known as prophenoloxidase activating enzyme (PPAE) acts upstream to cleave and turn PPO into active phenoloxidase (PO). Like PPO, PPAE also exists as an inactive zymogen and it is processed by a tightly regulated serine protease cascade in a step wise way into enzymatically functional form leading to the final melanin formation. As in other invertebrates, a recent in vitro study on the Drosophila PPOs suggested a direct binding of PPOs to bacteria and fungi which might play a role to initiate their activation  mutant with aberrant crystal cells , Zir  and Fondue. Drosophila TF is the only mammalian blood coagulation factor homolog (Factor XIIIa) found in the fly and uses Fondue as its substrate to form the blood clot. Unlike hemolectin (hml) mutants shown to affect only coagulation  expressed mainly by plasmatocytes is required in blood coagulation. Blood coagulation led by plasmatocytes is independent of both melanin production and phenoloxidase activity, which is also part of the wound healing process   primary clot formation during blood coagulation: larvae bleed following the puncture wounding and the primary clot forms in the wound gap; (2) scab and syncytium formation: the primary clot is further cross-linked and hardened by melanisation to form a scab while epidermal cells surrounding the primary clot migrate toward it and then fuse to form a syncytium; and (3) central syncytium formation: more epidermal cells are attracted to the initial synticium and a larger central syncytium forms. JNK pathway is activated in the epidermal cells of the syncytium in a gradient manner to emanate signals for the epidermal cells to move along or through the wound clot to rebuild a continuous epithelium with its basal lamina and apical cuticle lining. Crystal cells are the haemocyte required in the formation of the scab. The scab stabilizes the wound site, establishes a physical barrier to the external microbes, prevents the over-activation of JNK pathway which can result in chronic wounding and provides a scaffold for re-epithelialisation. Scab forming and wound closure are controlled by independent genetic and signaling pathways as re-epithelialisation can still be activated at the wound gap though it never heals in the absence of a scab  and the remote internal tissues in a process similar to systemic inflammation in mammals.In a study to reveal the genetic and molecular networks in control of systemic wound response after physical wounding in Drosophila embryo laser wounding model and it is revealed not surprisingly that a coordinated process exists involving myosin, E-cadherin, Echinoid, the plasma membrane, microtubules and the CDC42 small GTPase which respond dynamically during wound repair  to larvae. The ROS stress in the gut induces NO expression and transduces the signal to haemocytes by a NO dependent pathway  which give rise to both the myeloid and lymphoid lineage. Mammalian HSC possesses the ability to self-renew and the pluripotency to differentiate into a great variety of blood cells in response to signals from its microenvironment, which has been termed the HSC niche  while the mammalian JAK/STAT can be activated by a large group of cytokines and growth factors. Dom is the only transmembrane receptor upstream of one JAK kinase (Hop) and the one STAT transcription factor (STAT92E). Therefore the misexpression of a dominant-active form of STAT92E can also promote tumorigenesis in the eye of the Drosophila adult flies and melanotic tumor formation in the larva , Sima, activates full length Notch receptor under conditions of normal oxygen availability and commits the prohemocyte to the crystal cell lineage  the role of Hippo signaling pathway in control of cell growth and survival together with Scrib/Dlg/Lgl signaling pathway in cell polarity to regulate organ sizes;  was isolated 70 years ago. However only recently has Lgl been identified as a component of a signaling circuit in the regulation of apico-basal polarity in epithelial cells: Scrib/Dlg/Lgl  in the Drosophila eye imaginal disk and screening for the entire Drosophila genome, Pagliarini and Xu indentified Scrib as the promoting factor for the metastatic transformation of the otherwise benign tumor caused by overexpression of Ras oncogene alone (Pagliarini and Xu, Drosophila eye as an in vivo “test tube” to investigate genetic interactions during tumor progression has proved to be extremely fruitful in dissecting the Scrib tumor suppressor signaling pathway and Hippo pathway and human oncogenes and tumor suppressors such as Ras and PTEN. Critical reviews of the most recent progress in the use of Drosophila in cancer modeling and therapeutic potentials can be found elsewhere (Miles et al., Despite a very short life span, cancer research to investigate directly the tumor progression and invasion in Drosophila, the interplay of innate immunity mediated inflammation and tumor growth and invasion can be investigated accordingly. Of note is the establishment of Drosophila intestinal tumor model to study the molecular and cellular mechanisms linking inflammation and cancer pathogenesis (reviewed in Christofi and Apidianakis, Drosophila cytokines Upd1-3 have been reported to activate the JAK/STAT signaling in promoting intestinal stem cell proliferation upon enteric infection or JNK-mediated stress response and thus the innate immunity plays essential roles in gut tissue homeostasis (Jiang et al., Drosophila Ras oncogene in association with bacterial infection can result in the formation of intestinal dysplasia (Apidianakis et al., v12Scrib−/− model in the Drosophila eye disks, which has been used to offer complementary views of systemic innate immunity to tumor growth and invasion. Under the condition of established tumor, the Drosophila haemocyte could be recruited to the tumor site and tumor associated haemocytes are the major source of Drosphila TNFα, Eiger, to promote the growth and invasion of the tumor cells into other tissues (Cordero et al., Drosophila eliminates cells deficient for the polarity tumor suppressors Scrib or Dlg to maintain the tissue homeostasis and keep any malignant growth in check (Brumby and Richardson, v12Scrib−/− tumor was found to induce a systemic proliferation of haemocytes via the JNK-JAK/STAT signaling cross-talk conserved also in response to tissue injury. The disrupted tumor basal membrane recruited circulating haemocytes in a manner reminiscence of wound healing (Pastor-Pareja et al., Drosophila the anti-tumor effect of a systemic inflammation response induced by mechanical injury and provided critical insight into the cross-talk between the different signaling pathways in regulating the multiple step progression of tumor.Like other aspects of tumor progression that can be modeled and studied comparatively in Drosophila as the complementary genetic tool to dissect each of the hallmark processes and to offer fundamental insights into the underlying genetic and cellular basis of the disease. In future, the Drosophila model can continue to be used as the reductionist system to investigate more of the cross-talks between these fundamental cancer biological processes. For example, the contrasting roles of immunity to control tumor growth or to be hijacked by the tumor can be modeled in the fly in a temporal and spatial manner. The unique advantage of Drosophila to be used as a whole organism has started to show promising potential in cancer drug screening and testing recently (Dar et al., Cancer has a complex biology. As a rationalization, Hanahan and Weinberg identified six major successive changes in human tumor development (Hanahan and Weinberg, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A question that continues to be asked by Clinical Trials Units is ‘Should we invest in commercial trials software or should we develop our own solutions?' The answer depends on the expertise available within the organisation, volume and diversity of work undertaken by the Unit and of course the resources available. The benefits of using electronic technologies are well known; they promote better access and analysis of data as well as providing study results electronically.There are many commercial solutions available. These are often prohibitively expensive, require extensive training, management and support. They are not flexible or adaptable as there is usually no access to the source code so it is difficult to customise or extend the functionality.Trials units conducting publicly funded trials who have access to an experienced programming team having knowledge and experience of good clinical practice and current legislation could consider developing their own generic software solution. The pros and cons of this approach will be explored in this presentation along with comparisons with some of the commercially available solutions.The requirements for trial administration, data management, data cleaning, checking and extraction for analysis will be understood through experience and collaboration with trials teams. A well-documented and tested standard solution developed in-house can provide the benefits of commercial software coupled with the flexibility and quick response offered by a resident programming team. The professional expertise brought to a trials unit by a programming team with trials experience cannot be easily replaced by purchasing a software solution.


Manganese (Mn) is an essential metal and has important physiological functions for human health. However, exposure to excess levels of Mn in occupational settings or from environmental sources has been associated with a neurological syndrome comprising cognitive deficits, neuropsychological abnormalities and parkinsonism. Historically, studies on the effects of Mn in humans and experimental animals have been concerned with effects on the basal ganglia and the dopaminergic system as it relates to movement abnormalities. However, emerging studies are beginning to provide significant evidence of Mn effects on cortical structures and cognitive function at lower levels than previously recognized. This review advances new knowledge of putative mechanisms by which exposure to excess levels of Mn alters neurobiological systems and produces neurological deficits not only in the basal ganglia but also in the cerebral cortex. The emerging evidence suggests that working memory is significantly affected by chronic Mn exposure and this may be mediated by alterations in brain structures associated with the working memory network including the caudate nucleus in the striatum, frontal cortex and parietal cortex. Dysregulation of the dopaminergic system may play an important role in both the movement abnormalities as well as the neuropsychiatric and cognitive function deficits that have been described in humans and non-human primates exposed to Mn. Manganese (Mn) is an essential trace metal that is required for a number of enzymes important for normal cellular functions   imaging on 20 asymptomatic welders (exposed to welding fumes containing Mn), 20 subjects with idiopathic PD and 20 normal controls  but significantly lower level of [18F]-FDOPA uptake in the caudate nucleus relative to controls but no effect on the anterior or posterior putamen  with a smaller reduction in the caudate nucleus (~17%)  PET for vesicular monoamine trasnporter type-2 (VMAT-2) is more likely to represent structural changes in dopamine terminals than [18F]-FDOPA PET when it relates to studies with Mn.In the last decade there has been a great deal of debate in the scientific literature about the potential role of Mn on the etiology of idiopathic PD. Epidemiological studies indicate that long-term exposure (>20 years) to Mn is associated with idiopathic PD . Consistent with this hypothesis, several studies in early idiopathic PD patients show that reductions in [18F]-FDOPA uptake in the caudate nucleus are associated with deficits in working memory performance and executive function  in which there is extensive behavioral and neuroimaging assessment prior to (baseline) and at two different time points after initiation of Mn administration  with amphetamine challenge in order to measure both D2-dopamine receptor (D2R) levels and in vivo dopamine release  dopamine available for release. To answer this questions, a number of ex vivo neurochemical studies were performed in the caudate and putamen of the same animals in which PET studies were performed. The results show that when all control groups were combined (imaged-controls and naïve controls) and used as a referent group, there were no significant differences on the levels of dopamine and metabolites in the caudate and there was only an effect of Mn on dopamine levels in the putamen when compared to the naïve controls only  in frontal white matter  most studies on Mn-induced neurochemical and neuropathological changes have been focused on basal ganglia structures due to its association with movement abnormalities and parkinsonism, and (2) Mn accumulates to a high degree in the basal ganglia. Besides the suggestion from neuropsychological and cognitive tests of frontal cortex involvement in Mn-induced neurological dysfunction, a review of the literature brings to light a lack of neuropathological studies in which Mn effects on the cerebral cortex have been performed. It is only recently when neuroimaging studies have interrogated cortical regions to examine their susceptibility to Mn-induced neurotoxicity. In this context, our recent studies in non-human primates have reported proton MRS metabolite changes in Mn-exposed animals  decrease in NAA/Cr ratio in the frontal cortex white matter  and [18F]-fallypride (Kd = 0.14 nM) have made such studies possible. Several publications have now described the reliability of using [11C]-FLB 457 to measure in vivo dopamine release in the cerebral cortex of humans and non-human primates (Narendran et al., 11C]-FLB 457 binding potential reduction measured by PET was directly associated with the amount of extracellular dopamine release induced by the acute amphetamine administration (Narendran et al., in vivo dopamine release in the cerebral cortex using PET is an extremely valuable approach to understand the molecular basis of the working memory impairments observed in humans and non-human primates exposed to Mn. We are currently performing these types of studies in our Mn-exposed animals in order to make associations between in vivo dopamine in cortical regions and working memory performance.While the displacement of D2R specific PET ligands such as [In the last decade there has been significant progress using state-of-the-art neuroimaging and behavioral methodologies that have opened up a new understanding of Mn neurotoxicology. While historically the focus of Mn neurotoxicity has been associated with parkinsonism as a result of the high levels of exposure that occurred in the mining and processing of Mn ore and in other occupational settings, the last decade has brought about compelling experimental evidence that at lower cumulative doses of Mn that are likely to occur from occupational and environmental exposures, other non-motor neurological effects appear to be more prevalent and these seem to be associated with cognitive function deficits. The later may be the result of Mn producing brain chemistry and structural changes in cortical regions, and the frontal and parietal cortex appear to be sensitive targets. Lastly, because of its relevance to motor and cognitive domains, it is possible that dysfunction of the dopaminergic system could be a common mechanism by which Mn could have an impact on both cognitive and motor function deficits observed in humans and non-human primates.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 Village/Commune Safety Policy was launched by the Ministry of Interior of the Kingdom of Cambodia in 2010 and, due to a priority focus on “cleaning the streets”, has created difficulties for HIV prevention programs attempting to implement programs that work with key affected populations including female sex workers and people who inject drugs. The implementation of the policy has forced HIV program implementers, the UN and various government counterparts to explore and develop collaborative ways of delivering HIV prevention services within this difficult environment. The following case study explores some of these efforts and highlights the promising development of a Police Community Partnership Initiative that it is hoped will find a meaningful balance between the Village/Commune Safety Policy and HIV prevention efforts with key affected populations in Cambodia. On the 16th of August 2010, the Co-minister of the Ministry of Interior announced the Village/Commune Safety Policy as a priority policy for the Kingdom of Cambodia. The policy urged authorities at the commune level to ensure that there was no stealing, drug production or dealing, prostitution, child trafficking, domestic violence, gangsters, illegal gaming, use of illegal weapons or crime occurring at any commune in Cambodia [With regards illicit drugs the policy stated that authorities were to specifically:“Take action to cut off and eliminate production, dealing and use of illegal drugs at the village commune/Sangkat by following the guideline No 052 National Department of the Police dated 21st 2006 on the implementation of a warlike approach to fighting any drug crime and to especially focus the law on drug control[.”The policy has had negative implications for HIV prevention among risk groups including harm reduction programs; a fact not lost on the Government of Cambodia who have acknowledged that the policy has made it much more difficult to access people who use drugs and has made “service provision for their benefit very difficult due to the misunderstanding of the law enforcement officers, especially at the commune level ”.Although the Village/Commune Safety policy has further highlighted the direct impact that law enforcement policy and practices can have on HIV prevention, many agencies have actively been trying to find a balance between law enforcement and HIV prevention efforts among most-at-risk populations (MARPs) in Cambodia over the last several years. Recognising that law enforcement practices were negatively affecting HIV prevention among sex workers, men who have sex with men and drug users, UNAIDS began working with the National AIDS Authority on a MARPs Community Partnership Initiative (MCPI). The MCPI was being designed as a standard operating protocol that could be implemented to decrease the impacts of law enforcement practices in HIV risk environments. Specifically the MCPI was designed to,Restore the enabling environment so as to allow the effective and smooth delivery of all forms of services to all MARPs” – UN Official familiar with the MCPIUnder the MCPI and with support from USAID and the Global Fund to Fight AIDS, Tuberculosis and Malaria, Family Health International in Cambodia FHI360) has been piloting initiatives aimed at improving the enabling environments for HIV prevention among MARPs in Banteay Meanchey province. These pilot endeavours have been done in conjunction with the AIDS Secretariat of the Ministry of Interior and focus on strengthening a collaborative partnership among Provincial AIDS Committees/Secretariats, local authorities, police, military police, development partners, non-governmental organisations and members of the MARPs communities. During implementation of this pilot project the local authorities, health care providers and NGO staff conducted sensitisation information sessions to the police about the HIV prevention needs of MARPs and the role of the police in the HIV prevention enabling environment [60 has beThe police were made aware of the HIV programs working with these groups including the specific activities being implemented to support them. Early evaluations of these sensitisation efforts indicate that the police no longer use possession of condoms by sex workers as evidence for arrest and the police are discussing drug related arrests more carefully with other service providers resulting in them distinguishing drug dealers from drug users and then releasing drug users back to the community .These initial successes are building momentum and FHI360 is being funded by AusAID’s HIV/AIDS Asia Regional Project (HAARP) to conduct a similar pilot program with police in Phnom Penh. Furthermore, officials from the Ministry of Interior involved with the work in Banteay Meanchey are reportedly looking to expand the effort into other provinces. Furthermore, UNODC are also working closely with its partners in Banteay Meanchey and other provinces to ensure that law enforcement officials are working collaboratively with other sectors to enhance the HIV prevention efforts among drug users.“There are key officials from the Ministry of Interior who have been providing local and national political support to these pilot program efforts and this is leading officials to want to expand these efforts into Phnom Penh and Sihanoukville.” – UN Official familiar with the pilot projects.While the original efforts towards the development of a formal standard operating protocol for the MCPI were with the NAA, it became clear that ultimately the Ministry of Interior needed to be able to lead efforts that were being designed to work with law enforcement officials at the local level, especially in relation to HIV prevention among people who use drugs. The Ministry of Interior agrees and has now specifically requested that resources be redirected so that they can train and build the capacity of all of its law enforcement agencies to play a collaborative leadership role in HIV prevention among MARPs.“The Ministry of Interior are key players if we want to make a meaningful impact on the enabling environment for HIV prevention among drug users. There are currently renewed efforts being made to bring the Ministry of Interior further on board with HIV prevention efforts. We need to support these efforts with resources so that the Ministry of Interior can coordinate positive law enforcement efforts with the enabling environment for HIV prevention among MARPs.” – UN official familiar with the increasing involvement of the Ministry of Interior in HIV preventionIn addition to work on the enabling environment on the ground, efforts are also being made to reform police education with regards harm reduction. With support from HAARP, FHI360 has developed and begun to implement a harm reduction training curriculum for the Cambodian Police training academy. In November of 2011, the National Harm Reduction Curriculum was officially approved by the Cambodian Deputy Prime Minister and early evaluation has demonstrated positive results.· Training pre-post test results showed a 34 % increase (at least 27 out of 33) in answers provided that favoured a law enforcement approach and support of HR programs.· A comprehensive nine module curriculum on HIV, drug use and its link with HIV, harm reduction principles and practices and on the new drug laws is being adopted by six police academies around Cambodia .The MCPI project work being done in Banteay Meanchey is about to be reviewed by a delegation that includes the Ministry of Interior. With ongoing technical support from UNAIDS, UNODC, WHO, and FHI360 and in collaboration with the Ministry of Interior the lessons being learned in Banteay Meanchey are being used to develop a new Police Community Partnership Initiative protocol. The protocol may include the formation of Rapid Response Teams to be comprised of police, local authority, NGO representatives and other key stakeholders at the local level to refer MARPs away from police arrest and into HIV prevention services.It is clear that the Ministry of Interior in Cambodia is serious about improving the role of law enforcement in HIV prevention among MARPs groups and the development and implementation of the Police Community Partnership Initiative is a critical step towards the realization of this goal.The authors declare they have no competing interests.NT, KC, SL and NC discussed the initial concept of this case study presentation. KC and SL conducted background research into the issue of the village/commune safety policy in Cambodia. NT conducted interviews with key informants familiar with the issue in Cambodia and drafted the initial manuscript. GS and AW provided unique insights, guidance and information with regards to this issue in Cambodia. GS, AW and NC provided editing assistance to reach the final stage of this manuscript. All authors read and approved the final version of this manuscript.


We give a new explanation for why some biological systems can stay quantum coherent for a long time at room temperature, one of the fundamental puzzles of quantum biology. We show that systems with the right level of complexity between chaos and regularity can increase their coherence time by orders of magnitude. Systems near Critical Quantum Chaos or Metal-Insulator Transition (MIT) can have long coherence times and coherent transport at the same time. The new theory tested in a realistic light harvesting system model can reproduce the scaling of critical fluctuations reported in recent experiments. Scaling of return probability in the FMO light harvesting complex shows the signs of universal return probability decay observed at critical MIT. The results may open up new possibilities to design low loss energy and information transport systems in this Poised Realm hovering reversibly between quantum coherence and classicality. Discovery of room temperature quantum coherence in the avian compass Quantum biology is dealing with open quantum systems closely coupled to their many degrees of freedom environment. The environment exerts time dependent forces on the system through the coupling. Some of these forces change very rapidly compared to the excitation frequencies of the system and look random from its point of view. This “heat bath” destroys quantum coherence and moves the system into a mixed state rapidly. The average effect of the random forces can be described as a non-unitary time evolution of the system's density matrix.The speed of environmental decoherence can be characterized by the decay rate of the off diagonal  point Merging the pieces of classical, semiclassical and quantum aspects a new picture emerges. Systems well below the critical point have non-chaotic dynamics with zero generalized Lyapunov exponents and quantum localization lengths extending only for few states. Decoherence in these systems is slow and purity follows a power law decay We demonstrate this on a simplified model of chromophores in light harvesting complexes and argue that it is very likely that biological systems use this mechanism to tune their parameters Next we show results for ion  see . The effAt criticality not only purity changes from exponential to power law decay but so does the population of the chromophores. In The findings support a new approach to quantum biological systems. They are not just under the influence of environmental decoherence due to random noise but also driven by waves of the incoming photons. The photons are absorbed by the chromophores which initiates an exciton on one of the chromophores in an initial state which is concentrated on the selected chromophore. The purity of the system becomes


Environmental Health Perspectives (EHP) established the Paper of the Year Award in 2008 to recognize high-quality papers published in the journal  determine whether these changes persist in children at 7 years of age, b) examine the role of timing of exposure, and c) explore whether epigenetic inheritance plays a role in these findings. The authors are also coordinating an effort to bring together studies with data from the same platform for a meta-analysis of the effects of maternal smoking on newborns. The findings of Joubert et al. support the possibility that epigenetic mechanisms seen by DNA methylation may be associated with effects of maternal smoking during pregnancy.It is well known that children whose mothers smoked during pregnancy are more likely to have health problems such as low birth weight and asthma. Joubert et al. addressed the hypothesis that the diverse effects of maternal smoking during pregnancy may involve epigenetic modifications such as DNA methylation. The investigators obtained cord blood samples from a pregnancy cohort in the Norwegian Mother and Child Study (MoBa), and they used the Illumina Methyl450K platform to examine whether methylation changes were associated with smoking during pregnancy. Joubert et al. found cord blood methylation of genes in a pathway important for the detoxification of chemicals in tobacco smoke. They also identified the methylation of novel genes not previously implicated in the response to tobacco smoke, one of which is involved in fundamental developmental processes. Work is now in progress to EHP congratulates all the authors of this paper for their contribution to the environmental health science literature. This research is important because it demonstrates the value of using this approach to study mechanisms of epigenetic effects of in utero exposures to chemicals and other environmental factors.


Food security requires the development and deployment of crop varieties resilient to climate variation and change. The study of variations in the genome of wild plant populations can be used to guide crop improvement. Genome variation found in wild crop relatives may be directly relevant to the breeding of environmentally adapted and climate resilient crops. Analysis of the genomes of populations growing in contrasting environments will reveal the genes subject to natural selection in adaptation to climate variations. Whole genome sequencing of these populations should define the numbers and types of genes associated with climate adaptation. This strategy is facilitated by recent advances in sequencing technologies. Wild relatives of rice and barley have been used to assess these approaches. This strategy is most easily applied to species for which a high quality reference genome sequence is available and where populations of wild relatives can be found growing in diverse environments or across environmental gradients. Agriculture needs significant increases in productivity to satisfy the expected growth in demand for food in the next few decades. The impact of climate variability and climate change on agricultural productivity is likely to be a major constraint to achieving increased food production. This makes the development of crop genotypes with resilience to climate change an important strategy for food security. Innovations in crop improvement based upon application of advanced genomics tools may be a way to address this need. The delivery of these technologies will require significant efforts in coordinated development and delivery of improved germplasm . GenomicCrop evolution has been relatively rapid under human selection over the last 10,000 years of agriculture. However, it is built on a very much longer period of evolution of wild crop relatives and the plant groups from which they are sourced. Understanding the processes and history of crop domestication and the evolution of related wild species provides critical knowledge to guide the development of crop varieties that are resilient to climate change in the future.Analysis of wild plant populations provides evidence of factors contributing to success in periods of climate change. For example, hybridization between species may be an advantage in adapting to rapid climate change by providing new genetic combinations to cope with new environmental circumstances. Closely related species that can hybridize are more likely to survive than highly divergent species that cannot hybridize . AnalysiRecent fossil evidence suggests early diversification of groups of crop wild relatives such as the grasses . The cliDomesticated crop species are few in number compared to the total number of land plant species . A smallGenomics tools provide new options for accelerated domestication of new species to allow adaptation of agriculture to climate change .Domestication may have been a single genetic event with all the domesticated plants being descendent from the same wild parents or have involved a few or many independent domestication events with many wild plants contributing to the domesticated gene pool. This understanding may provide the opportunity to repeat the domestication of important crop species from a different or more diverse gene pool. Genome analysis may be used to guide this process.The center of origin of a crop species is the region from which the species is believed to have been domesticated. These are the environments that the crop plant was originally best adapted to survive at the time of domestication. Domestication from a different population selected by genome analysis may provide an opportunity to develop genotypes adapted to a new environment.Oryza sativa) was probably domesticated in China from wild O. rufipogon. The A genome clade of wild rice relatives is now considered to be most diverse further south with a center of diversity in New Guinea, Australia, and Indonesia. These locations may prove to be good sources of novel germplasm for rice improvement. Species from more temperate regions could be used to adapt rice to production in cooler climates.Genome analysis allows rapid identification of geographic centers of genome diversity. The center of diversity of a crop species is the region displaying the greatest genetic diversity of the crop species or its wild relatives. This may be distinct from the center of origin as plant species may have been domesticated in areas that are not those including the greatest diversity. Identification of these locations may provide new and diverse germplasm and define new environments for production of the crop now or in the future. Asian rice (The gene pools of crop species may be considered at several levels. Genomic analysis may have value at all of these levels. The primary gene pool is the gene pool of the plant found in domestication and usually the species from which the crop was domesticated. The primary gene pool includes those plants that are available for direct use in genetic improvement of the species. The secondary gene pool may include more diverse material from other species that can be accessed but with a greater degree of difficulty. This often includes other species in the same or a related genus . The terde novo assembly of sequence data may be necessary to detect all differences and advances in sequencing technology to make this routinely possible with large plant genomes will be a significant advance.Advances in DNA sequencing in the last few years have resulted in genomic sequence data becoming more readily available . Major eAnalysis of the genomes of plants growing along environmental gradients may provide a greater understanding of how plants adapt to climate variation under natural selection .Analysis of the genomes of plant genetic resources will become a key tool to enable their utilization in crop improvement for climate adaptation. Targeting of genetic resources from environments that match the one being breed for is an important strategy. Large scale sequencing of accessions in plant germplasm collections will provide a platform to enable these approaches .Increased utilization of wild crop relatives will remain a major strategy for adaptation of crops to the environmental factors associated with climate change. Many crop wild relatives remain poorly collected and are not yet represent well in seed banks. Climate change and human development risk loss of this genetic diversity making accelerated collection of crop wild relatives urgent. Rice illustrates this challenge. The closest wild relatives of rice are those from the A genome clade from which rice was domesticated . Recent The analysis of populations of wild relatives of barley  and riceIn these studies, wild plants were collected from diverse environments or along a sharp environmental gradient. Sampling of the same population over time as the climate changes could be simulated by this strategy. In only a few cases we can access samples that have been sampled from the same population over a significant period of time. Key findings were that adaptation to hotter or dryer environments was associated with increased diversity of biotic stress genes. Coping with abiotic stress may be confounded by overriding associated changes in the biotic environment .Productivity gains in crop production require elimination of constraints to utilization of more diverse germplasm. In some species the requirements of end uses are a major limitation. Market requirements for specific food or processing attributes that are complex or not well understood at the genetic level can greatly hamper attempts to use diverse adapted germplasm. Genomics tools that allow these traits to be readily selected for in breeding will assist by removing these as constraints to rapid climate adaptation . Food quHuman selection for quality may result in loss of environmental adaptation. Fragrance in rice is highly attractive to humans and adds significant value to rice. The sequencing of the rice genome allowed the identification of the genetic basis of this trait  due to tThe breeding of crops to cope with new pests and diseases will be a key strategy to allow plants to cope with new climates. Genes from wild populations will continue to be a major option but this may need to be complemented by the use of novel transgenes or genetic modifications.Technology advances will continue to be critical. Ultimately we need to be able to access whole genome information on all crop species and their wild relatives to be effective in rapid crop adaptation to climate. Ongoing developments in the chemistry of DNA sequencing and in information technology hardware and software will be required to allow these very large amounts of information to be captured and managed.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.


Whole genome and whole exome sequencing projects yield thousands of missense mutations with unknown functionality. Direct estimation of the sensitivity and specificity of bioinformatic algorithms predicting the impact of missense mutations on protein function requires a 'gold standard' or set of mutations with known functionality. In the absence of a gold standard, additional statistical methods are needed to estimate the accuracy of these algorithms. It has been shown informative predictions depend on the algorithm and sequence alignment employed and often algorithms disagree as to which mutations are predicted deleterious or neutral .n algorithms, there are 2" disjoint categories employed by the ABM model, which includes 2n + 3 parameters, and the BM model is a special case of the ABM model that includes 2n + 1 parameters. We use the expectation-maximization algorithm for parameter estimation.To investigate the level of agreement, disjoint categories of sets of mutations are defined depending on which algorithms predict which mutations to be deleterious or neutral. We have developed two statistical models called Bernoulli mixture (BM) and augmented Bernoulli mixture (ABM) based on the capture-recapture technique that employs these disjoint categories. Application of these models allows us to jointly estimate the sensitivities and specificities of each algorithm considered without the use of a gold standard and to estimate the proportion of deleterious mutations in a given set. These estimates may then be used to calculate the posterior probability of a given variant being deleterious. When considering We apply the models to two types of predictions of functionality: simulated and real predictions. Using simulated predictions, we accurately recover the true sensitivity and specificity values and report confidence regions. We show example posterior probabilities of a given variant being deleterious. When a gold standard is available, we show the sensitivity and specificity estimates reported the BM and ABM models closely match the sensitivity and specificity estimated directly using the true functionality status. To test our models on mutations without known functionality, we apply the models to mutations obtained from the exomes of four individuals which were sequenced at the Human Genome Sequencing Center at Baylor College of Medicine to identify cancer susceptibility genes for acute lymphocytic leukemia and lymphoma in children. Within each individual, we estimate posterior probabilities for each variant being deleterious and apply an intersection filter to look for deleterious mutations shared by the three affected individuals, but not in the unaffected individual.The BM and ABM models may be used to estimate the sensitivity and specificity of algorithms predicting the functionality of mutations without the use of a gold standard and to calculate posterior probabilities of a given variant being deleterious which may be used downstream in application of finding causal variants in next-generation sequencing.


Data models are used to capture and organise the elements of the data in a meaningful way so that they can be stored and utilised by computer systems and support clinical decision making. This paper presents the data modeling considerations within the ‘Clinical Trial Methods in Neurodegenerative Diseases’ (CTMND) project funded by the NIHR [The project adopts a holistic approach for the investigation of the suitability and efficiency of clinical observations in neurodegenerative diseases clinical studies. This ongoing research in novel clinical and surrogate outcome measures will be incorporated in an online data collection and analysis system to facilitate clinical trials and relevant research, taking into account, wherever possible, routinely collected NHS data.This paper presents ongoing research in the project’s data modeling aspects with the following objectives:1. To review the current state of the art data models for capturing clinical information from the available literature.2. To compare and contrast their features against the data management requirements of the project and outline the key factors that affected the adoption of a specific model for the CTMND project’s information system.A set of key papers and past reviews were collected from the currently available literature detailing the characteristics of standard data models used in healthcare such as CDISC’s ODM, Health Level 7 and others. The data models and associated approaches were compared and contrasted with each other by taking into account best practices and guidelines emerging from organizations such as the Object Management Group (OMG). Finally, having concluded in a specific modeling approach we were also able to look forward at the possibilities that a particular solution enables and propose a flexible way to model clinical trial data.This review highlights a number of key data management and organization considerations that affect the adoption of a specific data model given the project specifications and resource constraints. The key factors were Current Resources, Interoperability (with current and future systems), Documentation and Reference Implementation availability.Given the dynamic environment of clinical trials as well as the project’s objectives to propose novel outcome measures, we comment on the suitability of the Dual Model approach for the efficient organization of clinical study data but more importantly for its flexibility in modeling novel outcomes with minimal software maintenance. According to this approach, a handful of elementary data structures  are made available to a higher level model that is responsible for their ordering and semantics. Additionally we provide specific details regarding system implementation.


Developing new therapeutic strategies to achieve a functional cure for HIV infection is a central objective for contemporary AIDS research. A key obstacle towards a functional cure for HIV/AIDS is the paucity of information regarding the establishment and maintenance of the persistent reservoirs of latently HIV-infected cells which support the rapid reactivation of virus replication when antiretroviral therapy (ART) is stopped. Given the many and important similarities between HIV-infection of humans and SIV infection of macaques, it is very likely that crucial information on the nature of HIV reservoirs may come from studies conducted in SIV or SHIV-infected macaques that are treated with ART. While this area of AIDS research is still in its early stages, it is important to note that these studies have now become possible due to the availability of antiretroviral regimens that successfully reduce SIV or SHIV replication below detectable limits. Specific advantages of the non-human primate models for HIV latency, reservoirs and functional cure include the following: (i) possibility to conduct extensive characterization of the virus reservoirs and pathogenic processes in tissues (including elective necropsy); (ii) performance of in vivo pilot trials of new therapeutic approaches can be conducted in a timely and controlled fashion; (iii) developing and testing of “risky” interventions  that may pose significant ethical challenges in humans; and (iv) possibility to control for various clinical parameters that are very hard to control in humans . On the other hand, current limitations to this type of studies are their cost and the lack of standardized research resources . In this presentation, the potential and limitations of animal models of functional HIV cure will be discussed together with selected examples of therapeutic approaches that could be developed and tested in non-human primates.


The cell has an intricate quality control system to protect its mitochondria from oxidative stress. This surveillance system is multi-tiered and comprises molecules that are present inside the mitochondria, in the cytosol, and in other organelles like the nucleus and endoplasmic reticulum. These molecules cross talk with each other and protect the mitochondria from oxidative stress. Oxidative stress is a fundamental part of early disease pathogenesis of neurodegenerative diseases. These disorders also damage the cellular quality control machinery that protects the cell against oxidative stress. This exacerbates the oxidative damage and causes extensive neuronal cell death that is characteristic of neurodegeneration. Mitochondria are key molecular players in all cells performing many vital functions. They are the powerhouse of the cell, providing the cell with adenosine triphosphate (ATP) generated by oxidative phosphorylation (OXPHOS). Mitochondria have an important role in buffering calcium flux from the endoplasmic reticulum and the plasma membrane thus helping to maintain the spatiotemporal distribution of calcium in the cell. Mitochondria have enzymes essential for steroid synthesis and are the chief source of endogenous reactive oxygen species (ROS) which are produced by several mitochondrial enzymes including components of the OXPHOS system .Proper mitochondrial functioning is very important to neurons. Neurons have high energy requirements. They are terminally differentiated cells which consume a lot of ATP to maintain ion gradients across membranes for proper neurotransmission. Efficient mitochondrial transport and positioning are also critical because different regions of the neuron have different energy requirements. Active growth cones and presynaptic terminals need more ATP than other parts of the cell . Calciumα-ketoglutarate dehydrogenase; pyruvate dehydrogenase; glycerol-3-phosphate dehydrogenase; dihydroorotate dehydrogenase; the monoamine oxidases; and cytochrome b5 reductase ..69].Mitochondrial quality control is a relatively new field of research which has a lot of unanswered questions. A simple analysis of the events that follow when cells are treated with the commonly used mitochondrial uncoupler like CCCP clearly exposes the many caveats in our understanding of the functioning this organelle. On CCCP treatment, it is seen that the mitochondrial distribution changes from a spread out pattern to a cluster around the nucleus. Why do they cluster around the nucleus? Does this involve ROS mediated signalling between the mitochondria and the nucleus or between the clustered mitochondria themselves? On using a high resolution microscope it is seen that what appears to be a cluster of fused mitochondria is actually made up of many punctuate individual mitochondria. It is known that fission can segregate out damaged or depolarised mitochondria so that it can be removed but what determines the sites of this fission? How does the cell know how much of the mitochondria have to be removed from the electrically continuous mitochondrial network? Are there internal sensors which can sense the local membrane potential within the mitochondria which decide the sites for mitochondrial fission? Once the depolarised mitochondria are separated from the rest by fission, it can undergo mitophagy. How does the cell specifically direct the autophagy machinery to the damaged mitochondria without activating bulk autophagy? And finally, how does the cell decide when to switch from mitochondrial quality control to activation of apoptosis? in vivo magnetic resonance spectroscopy (MRS) based techniques to analyse mitochondrial function, mitochondrial research is progressing rapidly towards a clearer understanding of the mitochondria and their interaction with the rest of the cell.Our knowledge of oxidative stress and mitochondrial biology is still very rudimentary with a lot of unexplored questions. With the advent of sophisticated techniques like super resolution imaging, mass spectrometry based mitochondrial proteome analysis, and new


Antibiotic drug discovery is an indispensable process to combat aggressive ability of pathogenic microorganisms and emerging infectious diseases against health and well-being of people throughout the world. According to the updated and expanded data on natural products presented by Newman and Cragg , the utiStreptomyces griseus there has been a rapid escalation in antibiotic discovery from the genus Streptomyces (largest genus of Actinobacteria). Subsequently, members of this genus have become renowned as a prime source of natural antibiotics  are currently isolated from diverse environments and intensively studied for potential leads for antibiotic discovery programs. The rare actinomycetes are usually regarded as strains of actinomycetes whose isolation frequency by conventional methods is much lesser than that of streptomycete strains  apparently opine that these organisms nourish the current antibiotic drug discovery programs.


The application of Personalized Medicine strategies of matching specific disease genotypes and phenotypes with specific pharmaceutical drug treatment has shown tremendous efficacy in several important diseases. The most successful example is the targeting mutations of the epithelial growth factor receptor by small molecule antagonists of the tyrosine kinase in non small cell lung cancer. The expansion of this treatment paradigm into other diseases has led to new thinking considering the diagnosis and treatment of disease, including “Precision Medicine”, which seeks to provide a molecular taxonomy of disease that can be used for guiding targeted therapy in individual patients. Today we have only a cursory understanding of the patterns of actual uptake of drugs or their active metabolites at such targeted sites in the body. In the past such studies required extrinsic labeling of the parent drug (ie radioactivity in PET) that potentially changed the chemical and biological properties of the drug. New technologies such as MALDI-MSI mass spectrometry have revolutionized the label-less tracking of drugs within targeted disease tissue sites . A spect


Effective malaria control programmes prevent malaria transmission by promoting personal protection measures and effective vector control strategies, and providing appropriate case management with early diagnosis and effective treatment. The objective of the study was to understanding of malaria entomologist in relation to current malaria control in their area of activities and technical disciplines.A qualitative approach was adopted based on a semi structured interview with 30 individuals working at community-level in malaria endemic areas. Thematic content analysis was used to analysis the data.Although most of participants have been concern with the distribution and causation of problems of malaria control, few of them have addressed the issue of solutions. Participants had positive perceptions on their basic activities and opinions in relation to biologic and epidemiologic factors in their field work. In contrary, their perceptions in relation to malaria control policy and integrated management of vector control were rather negative.There was not feedback mechanism on malaria control activity among practitioners. Therefore, any problems due to the mismatch between the institutional tasks and individual role performance should be fed back into the health system and adjustment should be made. Greater emphasizes should be given to the choice of solutions.