Knowledge exchange portals are emerging as web tools that can help facilitate knowledge management in public health. We conducted a review to better understand the nature of these portals and their contribution to knowledge management in public health, with the aim of informing future development of portals in this field.A systematic literature search was conducted of the peer-reviewed and grey literature to identify articles that described the design, development or evaluation of Knowledge Exchange Portals KEPs in the public health field. The content of the articles was analysed, interpreted and synthesised in light of the objectives of the review.The systematic search yielded 2223 articles, of which fifteen were deemed eligible for review, including eight case studies, six evaluation studies and one commentary article. Knowledge exchange portals mainly included design features to support knowledge access and creation, but formative evaluation studies examining user needs suggested collaborative features supporting knowledge exchange would also be useful. Overall web usage statistics revealed increasing use of some of these portals over time; however difficulties remain in retaining users. There is some evidence to suggest that the use of a knowledge exchange portal in combination with tailored and targeted messaging can increase the use of evidence in policy and program decision making at the organisational level.Knowledge exchange portals can be a platform for providing integrated access to relevant content and resources in one location, for sharing and distributing information and for bringing people together for knowledge exchange. However more performance evaluation studies are needed to determine how they can best support evidence-informed decision making in public health. With an increased awareness of the need for evidence-informed decision making in public health, knowledge management strategies need to be employed to ensure information is easily accessible , tailoreKnowledge management is central to evidence-informed decision making, as it involves organisations and/or individuals creating, accessing, exchanging and translating knowledge (both explicit and tacit), usually in order to apply it to a particular policy or program challenge ,5. As thWeb portals are emerging as one information technology system capable of facilitating knowledge management, as they can help people to find the information they need, when they need it. Portals have evolved from simply being an efficient web tool for the one-way retrieval and transfer of information, to a platform for two-way collaboration and exchange among people in different organisations or professions, i.e. knowledge portals or knowledge exchange portals (KEPs) -11.It appears that KEPs can facilitate knowledge management through three core activities, depending on their available design features and functions -13: (i) A growing body of literature ,15 suggeHowever, KEPs are a relatively new form of online communication technology and from a design perspective, it is still not clear which features and functions work best to support knowledge management in public health. We therefore conducted a systematic review of the literature to better understand the nature of these portals and their contribution to knowledge management in public health, with the aim of informing future development of portals in this field.The review included analysis of the peer-review and grey literature to answer the following questions: 1) What are the common knowledge management design features of KEPs in the public health field? 2) How can KEPs assist in knowledge management for public health professionals? 3) Have KEPs been effective in terms of their uptake and facilitation of knowledge management in public health practice?ProQUEST Central; (ii) Web of Science Core Collection and (iii) EBSCO Host Research Collection  Both peer-reviewed databases and Google Scholar were searched with the following keywords and Boolean operators: (1) knowledge exchange portal OR web portal OR online OR website AND; (2) knowledge translation OR knowledge exchange OR knowledge transfer AND; (3) public health OR health.As there is no standard definition of a Knowledge Exchange Portal (KEP), we defined it broadly on the basis of two published definitions ,17 as a We included all articles  that described the concept, development, implementation or evaluation of a KEP in the field of public health. We set seven exclusion criteria in order to maintain a focus on web portals that could assist policy makers or practitioners in evidence-informed decision making in public health  decision making. Hence, articles were excluded if they described: (1) a business knowledge management tool designed to help internal employees navigate, understand and comply with organisational processes; (2) portals that aid in the management of health services or patient-specific data for the use of clinical decision-making; (3) online library catalogues; (4) portals delivering online education modules only ; (5) the field of knowledge translation and/or knowledge exchange more generally and did not include information on KEPs; (6) portals designed to support consumer health decision-making for commercial products; and (7) portals designed to facilitate genomic or proteomic sequence searching and/or molecular visualisation. Issues over inclusion or exclusion of articles were resolved by discussion between three independent reviewers .As the articles were mostly descriptive, we analysed the content of the articles and synthesised the evidence according to the review questions above. Issues over discrepancies concerning analysis were resolved between three authors  before reporting.Where the articles described portal design features or functions, we classified these features into the domains of knowledge management as defined by Lee et al.  and Goh The initial database and grey literature searches identified 2223 articles, of which 15 met the inclusion criteria  content e.g. email bulletins or newsletters etc. This is the case for portals containing online registries of public health evidence ,21,26, oKEPs can also be a platform for knowledge exchange by providing collaborative features (i.e. discussion forums) that enable communities or networks of practice to be established and maintained. ‘Communities of practice’ or ‘knowledge networks’ involve the sharing of explicit or tacit knowledge for a collective purpose. Three articles ,27,32 deIn six articles classified as evaluation studies ,23-25,32The three formative evaluation studies ,25,32 inTwo evaluation articles ,24 and oIn terms of portals contributing to evidence-informed decision making (EIDM) in public health, Dobbins et al.  conducteNine authors ,28,30,31Eight authors discussed the importance of promoting the portal to all user groups in order to generate and maintain use of the portal over time -27,32,33Three authors ,27,32 spWhile the published literature in this field is still evolving, this review demonstrates a wide variety of ways that KEPs can support knowledge management processes in public health. Public health KEPs may contain evidence libraries or registries, provide access to a range of epidemiological and demographic data, enable creation of new online content  and/or maintain online communities of practice for sharing of knowledge about public health policies, programs or services. One RCT  has demoIn our review, we found that features supporting the process of knowledge access  and knowledge creation  were the most popular design features in public health KEPs. The studies conducted by Lee et al.  and Goh In terms of KEP usage or uptake, the reviewed studies revealed that while portal use may increase over time, retaining users remains a problem ,24. HoweIt is important to note that while web usage statistics provide a quantitative indication of knowledge access, monitoring usage patterns does not infer evidence-informed decision making in public health. Performance evaluation models that help to measure how portals are assisting in knowledge management activity ,38 are sThis review also suggests some potential success factors that might be taken into consideration when designing, developing and maintaining a KEP for a public health audience. These include ensuring the portal has a user-centric design, promotional and funding strategies are sustainable and that online knowledge transfer and exchange activity remains beneficial for users.Our search strategy was limited to articles published in English only. Given that the information communication technology sector is rapidly evolving in some developing countries , we may have missed inclusion of articles published in other languages. Due to the difficulties associated with key word searching and comprehensively searching the grey literature, it is impossible to say we identified every eligible article for review; however our review process was systematic and covered a long time period. The findings of our review could be used with validity by public health staff that are considering designing and developing a KEP.KEPs can have design features that enable integrated access to relevant content and resources in one location, the sharing and distribution of tailored information and for bringing people together for knowledge exchange. Formative evaluation studies suggest that users want easily accessible and succinct information and collaborative features for knowledge exchange. Web usage studies reveal that while portal usage may increase over time, retention of portal users remains a problem. Evidence suggests that KEPs in combination with other knowledge management strategies can influence evidence-informed decision making in public health. However for the design of KEPs in this field to evolve based on the best available evidence, there needs to be more performance evaluation of KEPs in order to justify the resource investment over time.KEP: Knowledge exchange portal; RCT: Randomised controlled trial; KB: Knowledge broker; TM: Tailored and targeted messages; EIDM: Evidence-informed decision making.Dr Holly Seale holds an NHMRC Australian based Public Health Training Fellowship (1012631). Payment for presentations: Dr Seale has received funding from Sanofi Pasteur, GSK and CSL Biotherapies for investigator driven research and for conference presentations.EQ lead the design and conduct of the systematic literature review, including evaluating all articles for inclusion in the review, drafted the manuscript and finalised the manuscript with all authors for submission. CHS assisted in the conduct of the systematic literature review, including the evaluation of articles for inclusion in the review and in drafting and finalising the manuscript for submission. DC assisted in the conduct of the systematic literature review, including the evaluation of articles for inclusion in the review and in drafting and finalising the manuscript for submission. HS provided guidance in the conduct of the systematic literature review and participated in drafting and finalising the manuscript for submission. AM provided guidance in the conduct of the systematic literature review and participated in drafting and finalising the manuscript for submission. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/14/443/prepubList of individual databases searched through the online meta-databases*.Click here for file


Headgear is widely used in both work and leisure. Much research attention has been spent on optimizing impact properties of helmets , 2]. Ho. Ho2]. HThe literature on thermal effects of headgear was reviewed for the purpose of providing a sound basis for improving helmet design, and for effective future studies.Four topics will be addressed: (i) the effect on thermal physiology, health and performance, (ii) heat and mass transfer, (iii) methods for studying thermal effects of headgear, (iv) design considerations . Several topics will be detailed by other contributions to this conference from COST Action TU1101, which enhances the accessibility of the subject on ergonomics of headgear for the audience of this conference.


The role of neuroimaging in psychiatric neurosurgery has evolved significantly throughout the field’s history. Psychiatric neurosurgery initially developed without the benefit of information provided by modern imaging modalities, and thus lesion targets were selected based on contemporary theories of frontal lobe dysfunction in psychiatric disease. However, by the end of the 20th century, the availability of structural and functional magnetic resonance imaging (fMRI) allowed for the development of mechanistic theories attempting to explain the anatamofunctional basis of these disorders, as well as the efficacy of stereotactic neuromodulatory treatments. Neuroimaging now plays a central and ever-expanding role in the neurosurgical management of psychiatric disorders, by influencing the determination of surgical candidates, allowing individualized surgical targeting and planning, and identifying network-level changes in the brain following surgery. In this review, we aim to describe the coevolution of psychiatric neurosurgery and neuroimaging, including ways in which neuroimaging has proved useful in elucidating the therapeutic mechanisms of neuromodulatory procedures. We focus on ablative over stimulation-based procedures given their historical precedence and the greater opportunity they afford for post-operative re-imaging, but also discuss important contributions from the deep brain stimulation (DBS) literature. We conclude with a discussion of how neuroimaging will transition the field of psychiatric neurosurgery into the era of precision medicine. Long before the advent of neuroimaging, psychiatric neurosurgery was born. At the time, knowledge about the human brain’s functional anatomy was limited, and surgeons relied heavily on contemporary theory and scientific instinct to select neuroablative targets. In 1888, when Dr. Gottlieb Burckhardt removed the left frontotemporal cerebral cortex in six patients with psychiatric diagnoses, his surgical plan was based on results from animal studies and evidence of hypertrophic gyri in psychiatric patients  include anhedonia or depressed mood, with the addition of at least four more symptoms such as: change in sleep pattern, psychomotor status, or concentration; fatigue; feelings of worthlessness; or recurrent thoughts of death  has recently proposed a strategy for classifying all mental health disorders based on neurobiological measures as described above, termed the Research Domain Criteria (RDoC) project  defined in terms of functional neurobiological systems. A phenomenological diagnosis such as “OCD” would thus be re-classified according to dysfunction of fundamental constituent aspects of behavior and circuitry. Some of the key aspects of dysfunction in OCD include performance monitoring, response inhibition, and goal selection, all of which are classified under the RDoC construct of Cognitive Control (which is contained within the larger domain of Cognitive Systems). OCD may also project onto domains of Negative Valence Systems (Sustained Threat construct) and Positive Valence Systems (Reward Learning construct). Similarly, the diagnosis “MDD” may involve dysfunction in domains of Positive Valence Systems (Approach Motivation), Negative Valence Systems (Loss), Cognitive Systems (Cognitive Control), Arousal, and perhaps others.Another specifically mentioned motivation for creating the RDoC classification was to align the taxonomy of mental illness with neuroscience research , has been linked to several functional domains relevant to OCD and MDD, including fear response, anxiety, reward response, and memory. In a neuroimaging meta-analysis, the dACC demonstrated increased activity in patients who underwent fear or anticipatory anxiety conditioning , dorsolateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG), and posterior parietal cortex  loops , a technique that exploits the diffusion properties of water to determine fiber tract orientation  has primarily been used to treat severe, refractory OCD , located near Brodmann area 25, as a DBS target for depression (Mayberg et al., In summary, the emerging literature surrounding neuroimaging biomarkers may forecast an era of “precision surgery,” in which patient-specific neuroanatomy, elucidated by neuroimaging analysis, is used to refine surgical targets (Rück et al., The field of psychiatric neurosurgery has co-evolved with modern neuroimaging modalities. However, the relationship between psychiatric neurosurgery and neuroimaging has shifted dramatically since the field’s advent. Whereas neuroimaging was once used to retrospectively clarify procedural mechanisms, in the future, the same modalities will directly inform clinical decision-making, and, perhaps, will usher in an era of “precision surgery” for psychiatric disease.TGD, CBM, and SAS made substantial contributions to the conception and design of the work, drafted the work and revised it critically, gave final approval of the version to be published, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.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.


New technologies like new generation sequencing (NGS) and in-depthanalyses of large tumor series (as the ones included in The Cancer Genome Atlas - TCGA)have identified driver and associated mutations in most tumors and provided significantinsights on the molecular pathways of the different stages of carcinogenesis . In the GCRA programs are characteristically carried out in academic and tertiary care healthcenters with multidisciplinary teams providing diagnosis, genetic counseling, andfrequently, long term management of patients and their relatives (http://www.cancergen.org/). In addition to these academic models providingGCRA, additional models have been proposed over the years for extending access to theclinical practice, including a community-of-practice model that leverages the experienceand multidisciplinary nature of academic programs provided by collaborations of academiccenters with community-based providers in practice networks  of the United States of America proposed, in 1996, the launching of a national,cancer genetics network as a collaborative venture involving investigators from differentinstitutions The development of Clinical Cancer Genetics in Brazil over the past twenty years providesan interesting model for implementing comprehensive strategies in other underdevelopedcountries. In the mid-90s, several centers organized specialized clinics for assessinghereditary cancer risk, as well as for diagnosing and managing patients and families withhereditary cancer syndromes. These initiatives arose from the most advanced academic andresearch centers of public health in large cities of the Southeast of Brazil, and weresupported by research programs for generating expertise in genetic testing. Standards forcounseling, surveillance, testing and care were modeled on highly-structured programs inNorth America and Western Europe, involving multidisciplinary teams of specialized medicaldoctors, nurses and psychologists .In 2011, the BHCN was consolidated by establishing reference centers for research andclinical care of hereditary cancer. Currently, ten centers are established in publichospitals in cities like Belém (in the northern region and the Amazon basin), Salvador (inthe northeastern region), Vitória, Rio de Janeiro, São Paulo, Ribeirão Preto, Barretos (inthe southeastern region) and Porto Alegre (in southern Brazil), altogether providingapproximately 7,000 outpatient consultations and risk assessments of hereditary cancer peryear to the population assisted by the Public Health Care System (SUS) of Brazil. However,this coverage is still limited because these centers are located in urban areas that do notinclude large sections of the rural population and because their efficacy is constrained byshortage of properly trained, medical and non-medical, health care professionals and alsoby the fact that SUS does not pay for the genetic test to confirm cancer predisposition.Unlike most European and North American centers, genetic counseling in Brazil is mostlyprovided by physicians (MDs) because genetic counseling per se is not yetrecognized as a profession. Moreover, as SUS does not contemplate financial support forgenetic testing for hereditary cancer syndromes, the cost of most assays has been partiallycovered by funds originally destined for research rather than clinical assistance. Asignificant advance, however, took place in 2012, when the coverage of genetic testing byprivate health care plans became mandatory in Brazil, currently covering around 20-30% ofthe population.Despite these advances, the current coverage of oncogenetic services is presentlyrestricted to less than 5% of the Brazilian population. In fact, the vast majority of thepopulation relies on the Public Health Care System  whosepolicies and strategies to identify and care for patients and families with hereditarycancer are still unsatisfactory. To address this issue, the Brazilian National CancerInstitute  convened the Brazilian Hereditary CancerNetwork (BHCN), initially supported by public funding by the National Council forScientific and Technical Development (CNPq). Several research projects were initiallyimplemented for generating expertise in genetic counseling and testing protocols for themost common cancer susceptibility syndromes. In addition, specialized training programs forMDs and other health care professionals involved in hereditary cancer were implemented byBHCN participating centers. In 2009, a standard handbook was published for establishingnationwide guidelines for the detection, diagnosis, counseling, testing and surveillance ofhereditary cancer syndromes (Major challenges lay still ahead for the Brazilian Hereditary Cancer Network forfacilitating access of individuals with suspected or confirmed hereditary cancer to thepublic health care system for genetic testing, screening, and health management. Thesechallenges require recognizing the relevance of genetic counseling, testing and inclusionof genetic tests in SUS, developing initiatives for supporting institutions currentlyproviding clinical care in cancer genetics, dissemination of information to remote areas ofthe country, and creation of training programs and career opportunities for health careprofessionals in cancer genetics. Moreover, incorporation of novel diagnostic technologies,multidisciplinary approaches to patient care and establishment of collaborative researchprojects must be stimulated, aiming at a more comprehensive understanding of hereditarycancer in Brazil.


Bone fragility is recognized as one of the major comorbidities in Turner syndrome (TS). The mechanisms underlying bone impairment in affected patients are not clearly elucidated, but estrogen deficiency and X-chromosomal abnormalities represent important factors. Moreover, although many girls with TS undergo recombinant growth hormone therapy to treat short stature, the efficacy of this treatment on bone mineral density is controversial. The present review will focus on bone fragility in subjects with TS, providing an overview on the pathogenic mechanisms and some prevention strategies. Turner syndrome (TS) is a congenital disease caused by partial or complete loss of one sex chromosome, which occurs in 1:2500 female live births. Monosomy 45,X0 is present in about 45% of cases  has some limits, as the influence of body size on areal BMD (aBMD) interpretation . Smallerividuals . In factividuals , 11.The development of new bone imaging diagnostics, as peripheral quantitative computed tomography (pQCT), has allowed the evaluation of bone geometry and bone compartmental characteristics of TS subjects. In fact, pQCT provides precise measurements of three-dimensional bone density without the influence of bone size, and leads to assess trabecular and cortical bone density independently .In this respect, using pQCT, a low cortical BMD, with marked thinning of the bone cortex, and normal trabecular BMD of radial bone have been observed in TS adolescents , and simNevertheless, other studies have documented a reduction of both cortical and trabecular bone in TS subjects during and after puberty by using pQCT , whereasThese conflicting findings are due to different diagnostic imaging and characteristics of TS subjects . In partTherefore, different factors rather than reduced cortical BMD might predispose TS subjects to higher risk of fractures, such as altered bone geometry  and decrease of trabecular BMD or motor dysfunction .The bone microarchitecture is influenced by the continuous remodeling, a coordinated process between formation and degradation of bone, respectively, managed by osteoblasts (OBs) and osteoclasts (OCs). The by-products of these processes can be quantified in serum and urine, and used as markers of the balance in bone activity , 31. MarFurthermore, as skeletal muscle contraction represents a mechanical stimulus for bone development –37, it wThe mechanisms responsible of bone fragility in TS have not been completely elucidated. While some authors ascribed bone fragility to estrogen deficiency occurring during development and in adulthood , 20, 38,Figure Ovarian dysfunction is a common complication in TS subjects, and estrogen replacement therapy (ERT) is needed for the induction of puberty and for the maintenance of bone and cardiac health .The effects of estrogens on bone seem to be dose-dependent: low levels of exposure may increase the mechanical sensitivity of the periosteum, whereas higher concentrations may inhibit periosteal apposition, reducing cortical thickness . AlthougAn increased BMD due to augmented trabecular bone volume, and an unchanged cortical bone, has been demonstrated after 3 years of treatment with subcutaneous estradiol implants in TS young women . These fIn adult TS patients, the assumption of exogenous estrogen is important for prevention of osteoporosis  and in rFollicle-stimulating hormone (FSH) has a well-established role in reproduction, stimulating ovarian folliculogenesis, and estrogen synthesis, but recently has emerged also a role in bone metabolism. Some studies in mouse or human cells showed a positive direct or indirect FSH effect on OC differentiation and function .In particular, FSH enhances osteoclastogenesis and bone resorption directly by binding to FSH receptor expressed on OCs and their precursors , and indHigh FSH circulating levels have been associated with bone loss  and withGirls with TS have a biphasic pattern of gonadotrophin levels with high FSH and LH serum levels during childhood and at the time of expected puberty, in subjects with monosomy 45,X0 respect to those with mosaicism . A recenSHOX gene, located in the pseudoautosomal region of sexual chromosomes, seems to play a key role in growth failure typical of these subjects , associated with bone mineralization; insulin-like growth factor 2 (IGF2), placental growth factor (PGF), and prostaglandin endoperoxide synthase 1 (PTGS1) involved in bone repair, formation, and development (SFRP1) associated with Wnt signaling and affecting OB proliferation and differentiation  .The efficacy of rhGH therapy on BMD in TS is controversial , 73 alsoA recent study evaluated the effects of GH treatment on bone in 28 young adults with TS using HR-pQCT. The bone strength was evaluated through measurements of finite element (FE) analysis and polar moment of inertia (pMOI) . The autDifferent comorbidities of TS may affect bone health, such as obesity, diabetes, and some autoimmune disorders .Body composition is altered in TS with increased total and visceral fat mass, reduced lean mass, and augmented BMI , 75. MorCeliac disease and IBD represent other clinical conditions affecting TS patients, which may predispose them to bone fragility , due to Hypothyroidism affects up to 70% of TS patients, often with autoimmune cause , and it Strategies to prevent osteoporosis and fractures should been considered in TS subjects, just during pediatric age . In the Moreover, the use of non-invasive and radiation-free tools, such as phalangeal quantitative ultrasound (QUS), can be particularly useful for routinely assessing of BMD in children and adolescents with TS .Bone mineral density evaluation should be repeated frequently in TS patients who were most exposed to bone fragility, such as subjects undergone to glucocorticoid treatment, with experience of low-impact fracture or in absence of adherence to ERT  Figure B.The main measures to optimize bone health in TS are represented by the timely introduction of ERT and continuation of estrogen therapy through young adult life according to consensus guidelines , 27, 89 Many studies have found low serum vitamin D levels in TS subjects, which may contribute to the reduction of BMD , 33. MorAlthough data on impairment of bone density and geometry and fracture risk are often controversial, bone fragility is recognized as one of the major lifelong comorbidities in TS subjects. The pathogenetic mechanisms responsible of bone impairment remain to be well clarified, although estrogen deficiency and X chromosomal abnormalities represent important factors. An enhanced spontaneous osteoclastogenesis has been demonstrated to occur in girls and young women with TS before and after pubertal induction with ERT. This process seems to be more active in girls before puberty induction and supported by the high FSH serum levels observed at prepubertal stage, while in young women on continuous ERT, the effects on OCs seem to be mediated mostly by high RANKL levels. We recommended to consider the average age of 9 years as a crucial time point for the introduction of ERT. In the future, a neutralizing FSH antibody could be useful. In the meantime, a regimen combining the earlier introduction of ERT with rGH treatment in girls with TS could have the effect to reduce FSH levels and to preserve bone health in these subjects.All the authors wrote a section of the review and critically revised the manuscript.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.


Carotid artery stenting (CAS) is an important therapeutic strategy for patients with carotid artery stenosis. However, the potential influence of CAS on cognitive function in patients with carotid artery stenosis and cerebral lacunar infarction has not been determined. This study investigated changes in cognitive function associated with CAS and the factors related to these changes.This prospective cohort study comprised 579 Chinese patients with cerebral lacunar infarction and carotid artery stenosis for whom CAS was indicated, and a matched control group of 552 healthy individuals. Cognitive function before CAS and at scheduled intervals from 6 months to 3 years was assessed with instruments that included the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scale. Potential factors that might affect cognitive function were analyzed via logistic regression.The MMSE and MoCA scores of the patients before CAS were significantly lower than that of the control subjects. These scores were significantly higher 6 months after CAS and sustained or increased throughout the 3-year follow-up. Also significantly improved after CAS from baseline were scores for an alternating trail test, cube copying, clock-drawing, attention, and delayed recall in an auditory-verbal learning test. Logistic regression analyses showed that age greater than 65 y, little education, diabetes, and hypertension were independent risk factors for deteriorated MoCA scores 3 years after CAS.CAS was associated with significantly improved cognitive function in cerebral lacunar infarction patients with severe stenosis. The morbidity and mortality of stroke remains high in both developed  and deveCarotid artery stenosis caused by atherosclerosis is an independent risk factor for ischemic cerebrovascular disease , 8, and As a minimally invasive procedure, carotid artery stenting (CAS) is an important therapeutic strategy in carotid artery stenosis , 11. RecThe present multicenter prospective cohort study investigated changes in cognition in patients suffering both CLI and severe internal carotid artery (ICA) stenosis after CAS and the factors related to these changes. The cognitive function of Chinese CLI patients was monitored after CAS by utilizing the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scale, and factors that may affect changes of cognitive function in these patients were analyzed.The study was designed as a prospective cohort study to evaluate the influence of CAS on cognition function in CLI patients. The ethics committees of Shandong Provincial Hospital Affiliated to Shandong University approved the study protocol before performance of the study. All of the included patients provided written consent.Recruited were patients suffering both CLI and severe ICA stenosis, with CAS indicated. The patients were enrolled at sub-centers of the China Interventional Stroke Registry  from MarOnly patients who conformed to the following criteria were included: first onset of stroke within 1 week before enrollment; CLI confirmed by cerebral computed tomography (CT) or magnetic resonance (MR) imaging; unilateral or bilateral severe stenosis of the ICA, detected through digital subtraction angiography; and symptoms of cerebral ischemia related to ICA stenosis. Cerebral lacunar infarction was diagnosed in accordance with the National Fourth Revised Diagnostic Criteria for Cerebrovascular Disease of China in 1995 . CAS wasExcluded from the study were patients with cognitive disorders caused by nonvascular factors, such as congenital mental retardation; inability to complete the scale check; comorbidities such as severe heart, liver, or kidney diseases or complicated with malignancy; mental disorders including anxiety and depression; severe blood diseases or severe hemorrhagic tendency and not able to receive antithrombotic therapy; contraindications to antiplatelet medications or statins; vasculopathy or fibromuscular dysplasia caused by acute aortic dissection inflammation or acute arteritis, moyamoya disease, or radiotherapy; intracranial hemorrhage, hemorrhagic stroke, intracranial tumors, or diagnosed as intracranial arteriovenous malformation within 1 month before the enrollment; long-term substance abuse; symptomatic coronary artery disease requiring percutaneous coronary intervention; surgery within 1 month before enrollment, or planned to receive surgery within the upcoming 3 months; contraindicated to heparin or anesthetics.The control group consisted of healthy individuals recruited from the neurologic departments of the above centers, who visited for health screenings during the study period. Individuals in the control group were without any neurologic diseases, psychological disorders, or physical dysfunction as confirmed by CT or MR examination. The control group served as a baseline reference for cognitive function, to which patients in the test group were compared.The collected demographic and clinical data of patients included age, gender, fasting blood glucose, triglyceride, total cholesterol, systolic blood pressure, diastolic blood pressure, diabetes mellitus, coronary artery disease, smoking and drinking habits, education level, and handedness. In addition, patients with potential ICA stenosis and CLI who were scheduled to receive CAS underwent the following cerebral and vascular imaging examinations: color ultrasonography of the carotid artery, cerebral CT angiography, cerebral MR, and cerebral arterial angiography. The purposes of the imaging examinations was to assess brain structure, exclude other intracranial diseases, and obtain information regarding the location, morphology, and composition of plaques and the formation of collateral arteries compensatory to the artery stenosis. According to the general physical condition of the patient, some received CT perfusion imaging or MR perfusion weighted imaging, to assess regional cerebral blood flow.The analyzed potential risk factors for deteriorated MoCA scores 3 years after CAS were: age greater than 65 years, comorbidities of hypertension, DM, dyslipidemia, current smoking, alcohol drinking, and level of education. Little education was defined as ≤12 years of education. The diagnostic criteria for DM were 2 consecutive fasting plasma glucose ≥7.0 mmol/L or an oral glucose tolerance test 2-hour plasma glucose ≥11.1 mmol/L. Hypertension was defined as systolic blood pressure ≥140 mmHg and (or) diastolic blood pressure ≥ 90 mmHg.All patients underwent carotid artery color Doppler, brain CTA, brain MRI and cerebral angiography to characterize the vascular stenosis’ position, length, plaque, and collateral compensation and to determine the structure of brain tissue and exclude other intracranial disorders. Some patients underwent CT perfusion imaging, MR perfusion weighted imaging, or positron emission tomography to evaluate the regional cerebral blood flow and brain metabolism, depending on the condition of the individual.All of the patients received CAS treatment within 14 days of the onset of CLI. The CAS procedure was performed as previously described . BrieflyThe cognitive function of the patients was assessed according to scores on the MMSE and MoCA at enrollment in the study, and at 1, 6, 12, 24, and 36 months after CAS. The baseline MMSE and MoCA scores in healthy controls were also determined. Applications of the MMSE and MoCA were performed in accordance with the guidelines of the Chinese Interventional Stroke Registry System, as previously described . MMSE inThe Chinese version of the MoCA was adopted for cognitive appraisal . MoCA int-test was applied for the comparisons of continuous variables, and the chi-squared or Fisher’s exact tests for categorical variables. Multiple logistic regression tests were performed to detect potential independent risk factors for deterioration of MoCA scores 3 years after CAS, including age > 65 y, hypertension, DM, dyslipidemia, current smoking, alcohol drinking, and educational levels.Continuous variables are presented as mean ± standard deviation, and categorical variables as numbers and frequencies. The independent P-value < 0.05 was considered statistically significant.All of the statistical analyses were performed using SPSS16.0 statistical software. A Initially recruited into the study were 628 patients who fulfilled the inclusion criteria. Among them, 4 patients died after CAS , and 45 patients were lost during follow-up or failed to finish the cognitive assessment.P all > 0.05).Finally, 579 CLI patients with unilateral or bilateral severe stenosis of the ICA were included in the analyses . The parP < 0.05, all; P < 0.05, all).For CLI patients scheduled for CAS, at baseline the mean scores of the MMSE, MoCA, alternating trail test, cube copying, clock drawing, and attention and AVLT-delayed recall were all significantly lower than the scores of the control group (Of the analyzed potential risk factors for deteriorated MoCA scores 3 years after CAS, the multiple logistic regression analyses indicated that the potential independent risk factors were age > 65 y; little education; and hypertension .The primary objective of this multicenter prospective cohort study was to determine the effect of CAS on cognition in Chinese CLI patients with ICA stenosis. Cognitive function in this study was evaluated using two validated scoring systems, the MMSE and MoCA. The MoCA scale has been widely applied in clinics as a standard for evaluation of cognitive function; it is accepted that the sensitivity of MoCA is higher than that of the MMSE scale , 25. ThuOur finding that the baseline MMSE and MoCA scores for patients with severe ICA stenosis and CLI were significantly lower than those of the matched controls is not consistent with the results of previous studies , 27. TheThe potential mechanisms underlying the beneficial effects of CAS toward cognitive function in CLI patients with severe stenosis of the ICA may include the following. Firstly, CAS may improve cognitive function by improving or restoring cerebral perfusion. Indeed, it has been confirmed in both experimental  and clinSecondly, the optimized CAS procedure has been associated with reduced risk of recurrent stroke by preventing the progression of local atherosclerotic lesions . This suOur secondary objective in the present study was to determine the factors that may affect changes in cognitive function after CAS in these patients. It has been reported previously that gender, older age, and little education are risk factors for cognitive deterioration, whereas whether hyperlipidemia, diabetes mellitus, smoking, or drinking are risk factors is controversial . Most prThere have been reports that the CAS procedure itself may be associated with deterioration of cognition , or thatThe results of our logistic analyses indicated that older age, comorbidities such as hypertension and diabetes, and little education may be responsible for the deterioration of the cognitive function in these patients. These results indicated that risk factors that were related to the progression of atherosclerosis may also accelerate the deterioration of cognitive function in CLI patients with ICA stenosis. Therefore, optimal pharmacologic treatment for the control of blood pressure and blood glucose may also be important for the delay of cognitive dysfunction in these patients.The limitations of the study should be considered when interpreting the results. First, this was an observational cohort study, and the results should be confirmed in a randomized controlled trial. Secondly, although the MMSE and MoCA have been validated in previous studies to assess cognitive function, they may not reflect the overall cognitive function of patients. In addition, in this study regional blood was not evaluated to confirm an effective improvement in cerebral perfusion. Finally, the potential influence of the distribution and location of the infarct on the effect of CAS on cognitive function was not evaluated, because of the limited sample size. Future studies are needed to determine the patient subgroups who may benefit most from the CAS procedure with regard to cognitive function.In conclusion, our results indicated that, 6 months after the procedure, CAS was associated with significantly improved cognitive function in CLI patients with severe stenosis of the ICA, and these benefits lasted for at least 3 years after the procedure. These results show that randomized controlled trials to evaluate the potential influence of CAS on cognitive function are warranted.


From mid-January to mid-February 2015, all confirmed Ebola virus disease (Ebola) cases that occurred in Liberia were epidemiologically linked to a single index patient from the St. Paul Bridge area of Montserrado County  between the first visit to an HCF and their admission to an Ebola treatment unit. For three patients with available data, a fever (defined as a temperature >100.4°F [>38°C] taken with an infrared thermometer) was not recorded on arrival at the HCF. Of the eight patients, seven subsequently died from Ebola.Overall, 166 non-Ebola treatment unit health care workers in 10 HCFs possibly were exposed to the eight Ebola patients . The natObservations of the 10 HCFs found that health care worker exposures could have occurred for multiple reasons. Triage systems were inadequate with limited or no triage or isolation structures, no use or inappropriate use of infrared thermometers, limited ability to elicit accurate contact exposure history, and an incomplete understanding of the case definition (suspected or probable) by some staff members. Additional challenges included no use or inappropriate use of personal protective equipment, insufficient staff to support IPC activities, and inconsistent oversight by IPC partners.Ring IPC was a collaboration of the Liberian Ministry of Health National and Montserrado Incident Management Systems, Montserrado and Margibi county health teams, CDC, WHO, the African Union, and nongovernmental organization partners under the Liberia IPC Task Force. On January 30, members of the IPC Task Force met to formalize components of the Ring IPC approach, including identification of target HCFs, a focus on triage, involvement of external staff members to support triage, and coordination and definition of roles among partners. The purpose of Ring IPC was to provide intensive IPC support  to HCFs What is already known on this topic?The adoption of essential infection prevention and control (IPC) practices among health care workers, such as hand washing and proper use of personal protective equipment, is crucial to interrupting the transmission of Ebola.What is added by this report?From mid-January to mid-February 2015, all confirmed Ebola cases in Liberia were epidemiologically linked to a single index patient. Of the 22 confirmed patients in this cluster, eight (36%) sought and received care from at least one of 10 non-Ebola health care facilities. During this time, a focused IPC response effort, termed Ring IPC, was developed collaboratively to target health care facilities at increased risk for exposure to a person with Ebola. Rapid, intensive, and short-term IPC support was provided at these health care facilities following rapid needs assessments focused on triage procedures and personal protective equipment use.What are the implications for public health practice?The implementation of Ring IPC in Liberia might offer a useful model for rapid response to Ebola virus transmission and health care worker exposure in other settings. A comprehensive strategy remains critical to raising the level of IPC capacity nationwide; however, an appropriately targeted Ring IPC approach might be an effective supplemental strategy to focus IPC support in response to clusters of disease.Identified challenges were addressed by the national IPC Task Force developing training that targeted key personnel. Triage training, based on existing MOHSW-approved IPC training materials, was developed and provided to 47 African Union clinicians. These clinicians were deployed to 36 target HCFs in Monteserrado County to provide onsite daily triage mentoring and support for the duration of the high-risk exposure monitoring period, or for at least 2 weeks. Three nurses, previously employed by an Ebola treatment unit, provided similar triage support for one hospital. In addition, three 1-day triage training sessions were provided for more than 125 staff members working in three target HCFs. In Margibi County, a 1-day triage training session was conducted for 11 staff members working in five target HCFs, and African Union staff and nurses or other county health staff members provided ongoing triage mentoring and IPC support to seven target HCFs. This intensive IPC approach served to alert health care workers to recent Ebola virus transmission in their communities, identify additional contacts at HCFs where Ebola virus exposure had occurred, and provide a secondary source (in addition to contact tracing) of information on the health status of exposed health care workers.In response to heightened awareness of clinic needs, partners provided personal protective equipment and other essential IPC supplies to target facilities. Ring IPC partners in Montserrado County and the national IPC Task Force initiated an emergency release of a 1-month supply of personal protective equipment to priority clinics. Nongovernmental organization partners assessed and constructed triage structures when needed.During January 23–February 9, in response to the ongoing St. Paul Bridge cluster, four IPC rings were initiated in Liberia, three in Montserrado County and one in Margibi County . The firOverall, Ring IPC efforts appeared to be associated with an increase in the identification and isolation of suspected or probable Ebola patients. For example, three probable Ebola patients were identified through triage during training conducted at one target HCF in Montserrado County. Only one of the 166 exposed health care workers in the St. Paul Bridge cluster became infected with Ebola. This low prevalence of secondary infection among health care workers suggests that basic infection prevention principles were being observed by health care workers during this period. Nevertheless, triage was not always completely successful; the one health care worker who became infected with Ebola after Ring IPC activities were initiated actually sought care at his place of employment, an identified target HCF, and was permitted to enter without first being properly triaged as a probable or suspect Ebola patient.Included among the Ebola response efforts in Liberia was the creation in early September 2014 of a national IPC Task Force to support the MOHSW. The IPC Task Force served as a coordinating body to facilitate IPC planning and implementation of activities in both health care and non–health care facilities, as well as providing IPC guidance and technical assistance through policy development and standardization of IPC training and implementation tools consistent with MOHSW priorities. The national IPC strategy had focused on providing a comprehensive package of IPC training and support, through trained IPC specialists, at major health facilities throughout the country because of widespread Ebola transmission occurring at the time. This strategy includes promoting essential IPC practices among health care workers, such as hand washing and proper use of personal protective equipment. Although a comprehensive strategy remains critical to raising the level of IPC capacity nationwide, an appropriately targeted Ring IPC approach might be an effective supplemental strategy to focus IPC support in response to clusters of disease.The public health intervention described in this report was rapidly implemented and integrated into Liberia’s national Ebola response as a result of coordinated, collaborative efforts by multiple partners. Coordination and collaboration among the national Incident Management System, county health teams, CDC, WHO, African Union and nongovernmental organization partners was key to identifying gaps in IPC needs and preventing duplication of efforts. The initial ring was coordinated by the IPC Task Force under MOHSW leadership. In subsequent rings, the national Incident Management System and county health departments joined efforts with CDC, WHO, African Union, and multiple nongovernmental organization partners participating in initial discussions, planning, and rapid IPC assessments. In general, HCFs welcomed additional training, personal protective equipment provision, and triage mentoring and support. The placement of IPC staff members trained in triage at target HCFs following training was readily adopted by clinic staff.The implementation of Ring IPC in Liberia might offer a useful model for rapid response to Ebola virus transmission and health care worker exposure in other settings. This approach, however, might be most appropriate at the beginning or near the end of an outbreak, when specific chains of transmission can be identified and when HCFs can be identified and targeted based on their risk for encountering an Ebola patient when there is known active transmission in their geographical area. Urban settings present challenges to this approach, because persons might seek care at HCFs outside of their immediate community. Although limitations in both supplies  and human resources (appropriately trained personnel) might inhibit a timely response to initiating IPC activities, the Ring IPC approach might be used to prioritize these limited resources.The Ring IPC approach was developed rapidly and collaboratively in response to an urgent public health need; as such, data were not collected and aggregated systematically across all facilities, potentially limiting the generalizability of these results. Nonetheless, as a result of Ring IPC efforts, health care workers at HCFs in areas with recent active transmission are now better equipped and trained to rapidly triage, isolate, and refer suspected and probable Ebola patients to appropriate Ebola treatment unit facilities. As Liberia looks ahead, a new culture of IPC can be incorporated into the health system; a Ring IPC approach might be useful in minimizing the transmission in non-Ebola HCFs should new cases of Ebola occur.


The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. Current estimates project that global chemical production—currently growing 3% per year—will double every 25 years  and fission (Schizosaccharomyces pombe) yeasts are ideal models in which to conduct functional toxicological studies. Numerous metabolic and signaling pathways, along with basic cellular processes, are conserved with more complex organisms such as humans. Human homologs have been identified for a large number of yeast genes, with several hundred of the conserved genes linked to disease in humans  could metabolize arsenic in human urothelial cells. Harari et al. , and grow in suspension  screens have become an important tool in drug discovery  are not available due to the lack of barcode sequences in the mutants. These mutants may prove useful in follow-up analyses of conserved genes and pathways identified by chemical genetic screens in yeasts or bacteria.The nematode in vivo genetic and chemical studies (Pardo-Martin et al., in vivo approach in embryonic zebrafish, where a wide variety of developmental morphology and neurotoxicity endpoints are rapidly screened to understand chemical toxicity (Truong et al., Functional toxicology in more complex whole organisms is not straightforward, but new technologies offer encouragement for the future. The zebrafish model is useful in large-scale Traditional approaches for generation of knockout animals in mice remains a time-consuming and costly process that limits its utility in functional toxicology to confirmatory analysis.However, new systems facilitating deletions in animals can be used to selectively target genes for editing or mutagenesis (Miller et al., Inherent in high-throughput functional toxicology methods is the use of computational analyses to decipher toxicant mechanisms of action. Various studies have utilized overenrichment or Cytoscape software (Shannon et al., C. elegans, one is unable to examine a toxicant's target organs or systemic effects. The discovery of human disease models through orthologous phenotypes may address these concerns. For example, McGary et al. (C. elegans model for breast cancer, based upon analyses of genes shared between the model system and an organism displaying the disease under study. Similar analyses of functional data from unicellular organisms, cell lines, and C. elegans may reveal toxicant mechanisms associated with more complex biological processes.For a variety of reasons, functional toxicology has its limitations in the range of organisms discussed within this review. Less complex organisms such as yeasts, other fungi, and bacteria possess P450 enzymes Käppeli, , but they et al.  proposedIn whole organisms, throughput is the major barrier to progress in functional toxicology. In yeasts and bacteria, barcoded systems allow for the high-throughput examination of thousands of deletion mutants in parallel (Giaever et al., Functional toxicological screening methods, i.e., those that identify genetic requirements for chemical tolerance, are powerful, unbiased tools which provide unique mechanistic insights in the field of toxicology. High-throughput screens of chemicals of concern or unknown toxicity will allow toxicologists to formulate hypotheses related to their corresponding mechanisms and pathways of toxicity. Automation and deep parallel sequencing technologies will unquestionably increase the throughput of functional techniques, but extensive computational resources and knowledge will be required to implement screening systems and analyze the resulting data. Integration of functional assays across a variety of organisms can identify conserved modes of toxicity and direct studies most relevant to human health Figure . The fieThe 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.


Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gland from oxidative stress. The association of selenium, as well as intake of other micronutrients, with thyroid cancer is unclear.We evaluated associations of dietary selenium, beta-carotene, calcium, vitamin D, vitamin C, vitamin E, folate, magnesium, and zinc intake with thyroid cancer risk in the National Institutes of Health – American Association of Retired Persons Diet and Health Study, a large prospective cohort of 566,398 men and women aged 50–71 years in 1995–1996. Multivariable-adjusted Cox proportional hazards regression was used to examine associations between dietary intake of micronutrients, assessed using a food frequency questionnaire, and thyroid cancer cases, ascertained by linkage to state cancer registries and the National Death Index.Q5 vs Q1, 1.34; 95% CI, 1.02–1.76; Ptrend, <0.01), we observed no evidence of an association between quintile of selenium  or other micronutrient intake and thyroid cancer.With the exception of vitamin C, which was associated with an increased risk of thyroid cancer (HROur study does not suggest strong evidence for an association between dietary intake of selenium or other micronutrients and thyroid cancer risk. More studies are needed to clarify the role of selenium and other micronutrients in thyroid carcinogenesis. The past three decades have seen a rapid increase in thyroid cancer incidence in the United States (U.S.) and other countries 2O2 and reactive oxygen species While there has been research into dietary patterns as a whole, less work has been done to assess specific dietary constituents such as micronutrients and their impact on thyroid cancer risk. Additional research into the association between micronutrients and thyroid cancer may help further the understanding of the biological mechanisms involved in thyroid carcinogenesis. Selenium is an essential trace element that is found at higher concentrations in the thyroid gland than in other organs We therefore examined the association between dietary intake of micronutrients and thyroid cancer risk in the U.S. National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, a large prospective cohort of 566,398 men and women ages 50–71 years at baseline. The primary micronutrient of interest was selenium because of its established importance for proper function of the thyroid gland, its potential antioxidant properties, and the possible inverse association between selenium and other cancers The NIH-AARP Diet and Health study began in 1995–1996 with the mailing of an extensive baseline questionnaire to 3.5 million AARP members aged 50–71 years old and residing in six U.S. states  or two U.S. metropolitan areas . Information ascertained by the questionnaire included usual dietary intake over the past twelve months, use of individual and multivitamin supplements, alcohol intake, smoking history, height and weight at baseline, and other factors. Of the 566,398 individuals who were deemed to have satisfactorily completed the baseline questionnaire we excluded, in the following order, participants with proxy respondents , those who reported poor health or end stage renal disease , participants with a previous diagnosis of cancer other than non-melanoma skin cancer , those with extreme or missing values for total energy intake  and individuals with extreme values for daily selenium intake . The remaining analytic cohort included 482,807 participants . The NIH-AARP Diet and Health Study was approved by the Special Studies Institutional Review Board of the U.S. National Cancer Institute and the Institutional Review Boards from all participating institutions approved the use of these data.Participants accrued time in the study from the date of baseline questionnaire completion to the date of any cancer other than non-melanoma skin cancer, the date when a person moved out of the registry ascertainment area, death, or December 31, 2006, whichever occurred first. Incident thyroid cancers , topography code C73) The baseline questionnaire had a dietary component, which included questions about the frequency of dietary consumption during the past twelve months of 124 food items and the corresponding portion sizes of 100 of those food items. Intake frequency was recorded as one of ten categories ranging from “never” to “2+ times per day” for foods and “never” to “6+ times per day” for beverages. Additionally, each item included three possible portion size responses. The methods of Subar et al Cox proportional hazards regression Micronutrient intake was adjusted for total energy intake using the nutrient residual method Our minimal model was adjusted for age (continuous) and sex in the overall analysis and age in the sex specific analysis. Potential confounding variables were identified based on a review of the literature and previous studies on thyroid cancer using the NIH-AARP Diet and Health Study. Potential confounders were assessed using a backward elimination method in which we removed the least significant covariate in the model and assessed whether this changed the main exposure HR by more than 10%. We assessed for confounding by age (continuous), sex, body mass index , total calories (continuous), education , physical activity , race , smoking status , marital status , alcohol intake , and micronutrient intake . Effect modification was assessed using the likelihood ratio test comparing a model with the cross-product terms to one without.Finally, we tested the assumption that the risk of thyroid cancer was log-linearly associated with selenium and other micronutrient intake by comparing the linear model with a non-parametric regression curve obtained with restricted cubic splines Over a total of 4,406,634 person-years of follow-up we identified 592 incident thyroid cancer cases (257 in men and 335 in women) of which 406 were of the papillary histologic subtype (164 in men and 242 in women) and 113 (57 in men and 56 in women) were of the follicular histologic subtype. Select characteristics of the study population are presented by quintile of dietary selenium intake . ParticiQ5 vs Q1, 1.23; 95% CI, 0.92–1.65; Ptrend, 0.26). There was a statistically significant increase in risk of thyroid cancer for the highest versus lowest quintile of vitamin C intake in our multivariable model prior to adjusting for antioxidant intake , but not after . Although we observed evidence of a statistically significant positive linear trend for vitamin C, the HRs were highest for the fourth versus first quintile and were slightly attenuated for the highest quintile. For the remaining micronutrients in our study there was no clear evidence of a positive or negative association, or of a linear trend, between intake of any micronutrient and thyroid cancer risk.We also evaluated the associations between micronutrient intake and thyroid cancer separately by sex because of the higher incidence of thyroid cancer in women and suspected differences in the etiology of thyroid cancer by sex When we restricted the analysis to only participants with complete covariate information the results did not vary substantially from the presented data with an indicator variable for unknown values. There was also no indication that additionally adjusting for intake of the antioxidants vitamin C, vitamin E, beta-carotene, and folate in our multivariable model had an impact on the association with selenium or any other micronutrient (multivariable model 2 vs. 3). Finally there was no evidence that using sex-specific quintiles of micronutrient intake in men and women had a substantial impact on the results presented.Using a large prospective cohort study, we observed no evidence of an association between quintile of selenium intake and incidence of total thyroid cancer or the papillary and follicular subtypes. This was the first prospective study on this topic. We observed a suggestion of a positive linear relationship between increasing quintile of vitamin C and the risk of total thyroid cancer and the papillary and follicular subtypes, but no evidence of an association between thyroid cancer risk and calcium, folate, vitamin E, vitamin D, magnesium, or zinc intakes.Selenium is a biologically important micronutrient shown to have a preventive effect for cancers other than thyroid Another limiting factor of using an FFQ in our study population was that the participants were not asked about every possible contributor to dietary selenium. For example, dietary consumption of Brazilian nuts, the food with the highest selenium content In our analysis of other micronutrients and their association with thyroid cancer we saw evidence for an association with intake of vitamin C only. Higher intake of vitamin C appeared to be positively associated with thyroid cancer risk. Biologically, vitamin C has been shown to improve and mediate abnormalities seen in the levels of thyroid hormones and thyroid stimulating hormone in the serum of humans It is also possible that residual confounding may have contributed to our observed association between increasing quintile of vitamin C intake and thyroid cancer risk. Participants in the highest quintile of vitamin C intake had higher education, which has been associated with healthcare utilization and increased rates of thyroid cancer diagnosis Our study has several strengths. While previous studies have utilized case-control designs this study is the first to examine the association between selenium, and other micronutrient, intake and thyroid cancer using a large prospective cohort design, greatly reducing the possibility of recall and selection biases It is possible that exposure to essential micronutrients earlier in life, or over the course of an individual’s lifetime, may be more important in determining thyroid cancer risk. Although the NIH-AARP study utilized follow-up questionnaires that asked about diet at different points in the participant’s life, the follow-up questions were not designed to assess selenium and therefore were not used in this analysis. Future studies with information on dietary intake over the span of a person’s life could add valuable information to dietary studies on thyroid cancer risk. Finally, because the FFQ in this study was not designed to measure iodine consumption, we did not have information on daily iodine intake, which is important for thyroid function and may be a potential important confounding variable. However, iodine deficiency and the subsequent impact of not controlling for iodine intake on our study results is likely minimal, as iodine fortification of salt and other foods has occurred in the United States since the 1920’s In conclusion we observed no evidence of an association between thyroid cancer and quintile of selenium intake. Given the unexpected positive association observed for vitamin C, further evaluation of the association between vitamin C and thyroid cancer in other prospective cohorts is warranted. Valuable follow-up studies of selenium and thyroid cancer risk could evaluate selenium intake and intake of other micronutrients more objectively, such as by use of biomarkers.Table S1Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) for total thyroid cancer by quintile of micronutrient intake among men in The NIH-AARP Diet and Health Study.(DOCX)Click here for additional data file.Table S2Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) for total thyroid cancer by quintile of micronutrient intake among women in The NIH-AARP Diet and Health Study.(DOCX)Click here for additional data file.Table S3Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) for papillary thyroid cancer by quintile of micronutrient intake among men and women combined in The NIH-AARP Diet and Health Study.(DOCX)Click here for additional data file.Table S4Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) for papillary thyroid cancer by quintile of micronutrient intake among men in The NIH-AARP Diet and Health Study.(DOCX)Click here for additional data file.Table S5Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) for papillary thyroid cancer by quintile of micronutrient intake among women in The NIH-AARP Diet and Health Study.(DOCX)Click here for additional data file.Table S6Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) for total thyroid cancer by quintile of micronutrient intake among men in The NIH-AARP Diet and Health Study.(DOCX)Click here for additional data file.Table S7Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) for follicular thyroid cancer by quintile of micronutrient intake among men in The NIH-AARP Diet and Health Study.(DOCX)Click here for additional data file.Table S8Hazard Ratios (HRs) and corresponding 95% confidence intervals (CIs) for follicular thyroid cancer by quintile of micronutrient intake among women in The NIH-AARP Diet and Health Study.(DOCX)Click here for additional data file.


Despite advances in public health, medicine, and technology, infectious diseases remain a major source of illness and death worldwide. In the United States alone, unexplained deaths resulting from infectious disease agents have an estimated annual incidence of 0.5 per 100,000 persons aged 1–49 years . Other iSurveillance and rapid response for emerging infectious diseases remain cornerstones of CDC’s public health mission. There is a need for a holistic “One HealthPathologists are among the first to encounter infectious disease outbreaks through their collaborative work with diverse specialists including epidemiologists, clinicians, veterinarians, and microbiologists, and are thus in an excellent position to discover emerging infectious diseases . PatholoFor example, in 1993, an unexplained respiratory illness appeared in the Four Corners area  with reports of a influenza-like illness with high mortality rates in previously healthy young adults. The diligence of forensic pathologists in New Mexico in pursuing and performing autopsies was invaluable to the investigation . These aThe first breakthrough came via serologic testing at CDC with the detection of hantaviral antibodies in serum of patients who had succumbed to the illness . This waAt the outset of this investigation in 1993, only one nonpathogenic hantavirus had been identified in the United States; today, 24 hantaviruses with differing levels of pathogenicity have been identified in the Americas. This recognition of New World hantaviruses, coupled with a better understanding of hantavirus pulmonary syndrome, has resulted in critical improvements in the rapid recognition and clinical management of the disease and better understanding of the natural reservoir (rodents) and mode of transmission, all of which have greatly improved the ability to implement control and prevention measures, with emphasis on the critical role of individual communities.In 1995, another pulmonary outbreak was reported, this time in Nicaragua, with several hundred cases and many deaths. An important difference with this outbreak was that instead of the clear fluid usually observed accumulating in the lungs, frank hemorrhage was detected . InitialBalamuthia, and microsporidiosis (Transmission of infections from a single donor to multiple recipients through organ transplantation has been detected increasingly in recent years. Some infections identified at CDC as novel associations with solid organ transplants include West Nile virus (WNV), lymphocytic choriomeningitis virus, rabies, ridiosis –11. A yoridiosis . Followiridiosis , and theCause of death evaluation is an important component of the investigative process for emerging infectious diseases. When evaluating potentially infectious diseases as the causes of unexplained deaths, the use of autopsies has a number of advantages over death certificates: 1) availability of human tissues allows for enhanced diagnostic capacity and results in accurate determination of cause of death; 2) insights into pathogenesis and route of infection are gained; 3) rapid public health notification of findings is possible; and 4) recognition of additional infections not on death certificates is possible. The systematic collection and evaluation of this additional information affords an important opportunity for enhancing infectious disease surveillance. Monitoring of unexplained deaths and critical illnesses via autopsies at the state and local levels yields vital information about the actual numbers of cases of infectious diseases and provides insight into strategies for prevention.The New Mexico Office of the Medical Investigator created a Medical Examiner Syndromic Surveillance System (Med-X) for all fatal infectious diseases, which can be used in medical examiner jurisdictions ,14. A baBOXInfluenza-like symptomsFever and respiratory symptomsAcute encephalopathy or new onset seizuresDescending paralysis, polyneuropathyNew fatal rashNew jaundiceAcute bloody diarrheaUnexpected deathStreptococcus pneumoniae (37 cases), Streptococcus pyogenes (eight cases), and Haemophilus influenzae (five cases), as well as one case each of Mycobacterium tuberculosis and botulism and two cases of human immunodeficiency virus (HIV) infection. These findings indicate the value of pathologists conducting routine microbiologic testing in cases that come under their jurisdiction and have symptoms predictive of infection.In New Mexico during 2000–2002, a total of 6,104 medical examiner cases were examined. Of these, 250 met entry criteria , of which 141 (56%) decedents had a target pathologic syndrome and 127 (51%) were found to have an infectious disease. Three symptom sets were found to be highly predictive of infection in an otherwise unexplained death: 1) fever and respiratory symptoms (72%), 2) influenza-like symptoms (65%), and 3) encephalopathy or new-onset seizures (50%); sudden unexpected death (19%) was found to be less likely to represent an infection. Furthermore, in 81% of infectious disease cases, an organism-specific diagnosis was determined, with 58% representing notifiable conditions in New Mexico, including Another surveillance system using cause of death as a tool, Surveillance of Probable Infectious Etiology for Unexplained Death (UNEX), was initiated in 1995 as part of the CDC Emerging Infections Program in California, Connecticut, Minnesota, and Oregon. The goals of UNEX are to identify novel or newly emerging pathogens; to identify sudden, unexplained deaths attributed to known pathogens; to monitor the epidemiologic features of fatal infections; and to improve diagnostic postmortem testing . SourcesA Med-X surveillance system based on the New Mexico model also was initiated in Minnesota in 2006, enabling further description of infectious etiologies of death during 2006–2011. During this period, an average rate of 12 infectious deaths per 100,000 population was identified, encompassing 1,099 cases captured by UNEX and Med-X combined . In all three groups, males predominated, and UNEX identified 70 critical illnesses and 228 deaths in persons aged <50 years who were previously healthy and had specimens available for testing . Overall, during 2006–2011, the etiology for 29% of cases that had a specimen available for testing was determined. Cases with a respiratory syndrome were most commonly explained and sepsis/shock was the next most commonly explained syndrome. Examining the method of diagnosis in the explained UNEX subgroup cases revealed that, whereas most pathogens were detected by PCR (including both pathogen-specific PCR and 16S-PCR), other techniques such as culture and IHC also were very useful.Correlating laboratory findings, clinical features, and pathologic evidence to establish a causal relationship allows for the detection of organisms that otherwise would likely be missed. However, death investigation as a surveillance tool is not without its challenges. One hurdle commonly encountered was the identification of potential pathogens that are not the primary cause of a syndrome or death. Another obstacle was the resource-intensive nature of the surveillance and additional testing and materials required of medical examiners, pathologists, and public health staffs and laboratories.Effective use of basic and advanced diagnostic tools with ongoing development of new tools, a multidisciplinary approach, and vigilance by all critical partners are important in maintaining the partnership between pathology and public health. Tapping into the individual skills of clinicians, epidemiologists, microbiologists, veterinarians, pathologists, research scientists, and public health officials, especially in cases of unexplained deaths, contributes to the overarching goal of protecting the public from emerging infectious diseases and threats.


Prognosis is the main limitation of interceptive treatment of Class IIImalocclusions. The interceptive procedures of rapid maxillary expansion (RME) andface mask therapy performed in early mixed dentition are capable of achievingimmediate overcorrection and maintenance of facial and occlusal morphology for afew years. Individuals presenting minimal acceptable faces at growth completionare potential candidates for compensatory orthodontic treatment, while those withfacial involvement should be submitted to orthodontic decompensation fororthognathic surgery. To investigate cephalometric variables that might predict the outcomes oforthopedic treatment with RME and face mask therapy (FM).  Cephalometric analysis of 26 Class III patients (mean age of 8 years and 4months) was performed at treatment onset and after a mean period of 6 years and 10months at pubertal growth completion, including a subjective facial analysis.Patients was divided into two groups: success group  and failuregroup . Discriminant analysis was applied to the cephalometricvalues at treatment onset. Two predictor variables were found by stepwiseprocedure.  Orthopedic treatment of Class III malocclusion may have unfavorable prognosis atgrowth completion whenever initial cephalometric analysis reveals increased loweranterior facial height (LAFH) combined with reduced angle between the condylaraxis and the mandibular plane (CondAx.MP).  The results of treatment with RME and face mask therapy at growth completion inClass III patients could be predicted with a probability of 88.5%. Orthodontic success or identification ofwhich patients would benefit from early orthopedic treatment performed to disguiseskeletal discrepancy requires growth prediction.,-Fudalej et alFrom this perspective, the aim of this retrospective and longitudinal study was toselect a model of cephalometric variables capable of identifying differences in thefacial growth of young Class III patients subject to classic orthopedic treatmentprotocol (RME + FM).The research project that resulted in the development of the present study was approvedby the Institutional Review Board of Sacred Heart University under protocol number117/11. The sample comprised 26 patients, 11 boys and 15 girls, whose initial mean agewas of 8 years and 4 months. All patients had maxillary deficiency and/or mandibularprognathism with Class I or Class III malocclusion in mixed dentition. Patients weresubmitted to RME/FM therapy performed by the same group of clinicians, understandardized procedures. Patients' records were filed at the Center of Surgery andOrthodontics, Bauru, São Paulo/Brazil. In selecting the sample, the following exclusioncriteria were considered: previous orthodontic treatment, presence of craniofacialanomalies and significant facial asymmetries.,,The diagnosis of Pattern III facial growth was determined on the basis of subjectivefrontal and profile facial analysis,The average duration of active orthopedic treatment (RME + FM) was of 6 months. Thechildren began using face mask after expansion was considered clinically evident, for atleast 10 hours a day . Treatment finished when positive overjet orovercorrection were obtained .Patients were monitored after interceptive treatment had been carried out and reassessedafter an average period of 6 years and 10 months, without any type of retainer, at theend of pubertal growth (mean age of 15 years) which can be detected by biologicalindicators such as full pubescence for the boys and two years after menarche for thegirls. Whenever necessary, hand-wrist analysis was conducted on the search for IJ stageof the radius, in accordance with maturation indicators and pubertal growth spurt,,In this phase, all parts comprising the sample were assessed by the same evaluator inorder to determine whether interceptive treatment was successful or not, in accordancewith the criteria for subjective facial analysis.,The successful group comprised 21 patients who, at growth completion, fulfilled theesthetic and functional requirements necessary to be classified as estheticallyacceptable, based on a minimum criteria for facial balance, absence of or smallasymmetry, and the possibility of having passive labial seal in accordance withparameters previously established.,,Five patients were classified as unsuccessful, being considered as unsatisfactory interms of facial balanceLateral radiographs taken at treatment onset were analyzed and adjusted under amagnification factor of 9%. Identification of cephalometric landmarks was based onclassic definitions available in the literature.Cephalometric analysis was based on a basicranial reference systemThe 18 cephalometric measurements generated ten linear and eight angular measurements,as shown ino for angularmeasurements and from 0.35 to 1.34 mm for linear measurements.The error of the method of all cephalometric measurements was assessed by means of tenradiographs randomly selected. There was a two-week interval between the first andsecond assessment. T-test was used for intraexaminer systematic error calculation,whereas the random error was calculated by Dahlberg's formula.Discriminant analysis was applied to the cephalometric values of the 26 patients attreatment onset, and the stepwise method was used to identify, among the 18 variablesstudied, the smallest group that could point out any differences between the two groupsdetermined at growth completion: successful and unsuccessful. In order to attain thebest discrimination model, the first phase of analysis consisted in selecting the mostimportant variables in order to divide the groups into successful and unsuccessful.To verify the normality of groups, Shapiro-Wilk test was employed, with significancelevel set at 5% (P < 0.05).1), for the total sample and for both groups  is shown inDescriptive statistics for all cephalometric variables in the first observation phase. In order to attain a betterdiscrimination model that could anticipate the prognosis of an early malocclusion ClassIII treatment, the stepwise procedure was used to select the variables, using F = 3 inorder to keep or remove the variable from the model. When the smallest group ofvariables was selected, the predictive power (classification power) of the model wastested by means of discriminant analysis. An equation was then developed and applied toall 26 cases, and the total prediction model was calculated. This last procedureprovides a prediction model that allows a new patient to be included in each one of thegroups. The stepwise procedure identified satisfactory predictors and generated atwo-variable model that produced the most efficient division between the two groups. Thevariables selected were anterior lower facial height (ALFH) and inclination of thecondylar axis with the mandibular plane (CondAx.MP), a plane that represents themandibular body, passing through Goi and Me points , i.e., the mean values of the centroid group for both groups, is calculated on thebasis of data presented in,,,,Interceptive treatment of Class III malocclusion complies with a protocol most likely tobe the most uniform in Orthodontics, and which although upheld by undeniableefficiency,That was the objective of this research. A group of 26 patients submitted to RME/FMtherapy had their lateral radiographs of the face assessed before treatment and after a6-year follow-up, without any type of retainer, by the end of facial growth (mean age of15 years old). The maturation status was determined by biological indicators andconfirmed by hand-wrist radiograph assessmentThe criteria provided by subjective facial analysis were used to divide the groups atactive growth completion, a critical moment for the definition of the therapeuticprocedure and, hence, for the success or failure of interceptive therapy. Such criteriawere then associated with the identification of predictive measures with significantprognostic power at treatment onset of Class III patients. Facial analysis was used toidentify positive and negative facial features and, therefore, suggest a method to treatthe occlusion. Success or failure of orthopedic treatment requires growth prediction. Noaccurate methods employed to predict the future of mandibular growth are yetavailable.,,All 21 patients in the successful group were considered acceptable according to thesubjective facial analysis criteria.All five patients in the unsuccessful group presented sagittal imbalance, severe enoughso that it could be identified even by frontal assessment. Straight or concave profileconfirms studies that brought out a direct relationship between profile convexity andunpleasant esthetic appearance,,,,,The results obtained, with 80.7% of the sample considered as successful, confirm thepresupposed efficiency of the orthopedic correction protocol (RME/FM) employed as anintervention to treat Class III malocclusion. These data corroborate those found in theliteratureTaking the aforementioned information into account as well as the main purpose of thisresearch, the following question arises: Could patients destined for different resultsby the end of growth, whether successful or unsuccessful, have a prognosis defined apriori, i.e., before interceptive treatment is performed?,,,,,,Comparison between the successful and unsuccessful groups, carried out by means ofdiscriminant analysis applied to cephalometric data obtained at treatment onset,revealed two variables with predictive power: ALFH and condyle inclination in relationto the mandibular plane. In practical terms, the smaller number of variables included inthe discriminant analysis, the more relevant it will be.By means of discriminant analysis, Baccetti et alMoon et al,Therefore, it seems reasonable to admit that, in both studies,In a retrospective study, based on the results of orthopedic treatment (RME/FM)performed in 64 Class III patients, Ghiz, Ngan and Gunel,Moreover, changes in facial height can also be considered, since posterior facial heightor the length of the ramus (Co-Goi), obtained by Baccetti et al,Franchi et al,Thus, in general, it seems that mandibular shape and growth are more important than theinitial maxilomandibular sagittal relationship for a long-term prognosis of early ClassIII malocclusion treatment.,,From this broad perspective, comparison between our results and those yielded by otherresearchesThe limitations of this process of identifying variables capable of expressingprediction and allowing a prognosis are as evident as the possibilities that wereraised. The greatest limitation is expressed in the large number of predictors found andin the rare repetition of variables in the predictors models found in the literature. Asusual, the search for knowledge should be ongoing. It seems reasonable to consider thatincluding the predictors that occur with higher frequency in the researches carried out,for instance, the gonial angle, the changes in mandibular shape and size as well as theinformation regarding heredity, in the analysis model, can enhance the prognosticability.Based on the results of this retrospective and longitudinal study conducted with youngClass III patients who underwent an interceptive orthopedic treatment protocol (RME/FM)and were assessed by the end of facial growth, it is reasonable to conclude that anunfavorable prognosis can be predicted when cephalometric analysis carried out attreatment onset reveals that patients present, at the same time, increased ALFH anddecreased value of the angle between the condylar axis and the mandibular plane(CondAx.MP). The outcomes at active growth completion of an interceptive orthopedictreatment performed in Class III patients can be predicted with a hit probability of88.5%.