Sarcopenia has been recognized as a progressive and generalized skeletal muscle disorder leading to loss of strength, muscle mass, and function. It is associated with an increased likelihood of adverse outcomes like falls, fractures, physical disability, and mortality. International consensus groups continue providing new definitions and clinical cut-off points despite over a decade of work in this area. Thus, the purpose of this research was to determine the prevalence of sarcopenia using two of the most current operational definitions (Foundation of NIH Sarcopenia Project (FNIH) and the European Working Group on Sarcopenia in Older Persons 2 (EWGSOP2)). Our cohort of acutely hospitalized older adults was formed from combining data from two randomized controlled trials and one cross-sectional observational study. Testing during hospitalization included measures of: demographics, body composition (DEXA), physical function tests, psychological wellbeing and independence questionnaires, and chart review. These were used to analyze the cohort according to three main groupings of low physical performance, low muscle strength, and low lean mass. We compared multiple tests and cutoffs for each of the three groupings under the FNIH and EWGSOP2 definitions, which varied 3% for low lean mass up to 48% for tests of low physical performance. After examining the efficacy of each cutoff, we evaluated the differences between FNIH and EWGSOP2. In our cohort, the prevalence of sarcopenia was 15.79% by EWGSOP2 and 13.59% by FNIH. The groupings within FNIH and EWGSOP2 were found to be near identical across almost all measures despite the definitions’ discrepancies in cutoff points.


Cerebral venous thrombosis causes disability from venous infarct and hemorrhage and potential mortality. Anticoagulation improves survival and disability outcomes, yet direct oral anticoagulants are currently not indicated in cerebral venous thrombosis due to lack of evidence, despite being on the market for nearly a decade. This systematic review will collate evidence of reported safety and efficacy of direct oral anticoagulant therapy in cerebral venous thrombosis.A search strategy was developed with a research librarian and registered on a protocol database (PROSPERO CRD42017078398). All published studies from MEDLINE and EMBASE up to February 2019 containing patients diagnosed with cerebral venous thrombosis who were treated with a direct oral anticoagulant  will be included. A risk of bias analysis will be performed to evaluate quality of studies overall.Current guidelines in the treatment of cerebral vein thrombosis dating back to 2011 from the American Heart Association/American Stroke Association endorse the utility of anticoagulation for the treatment of cerebral vein thrombosis; however, they did not support the use of direct oral anticoagulants. Updated guidelines from the European Stroke Organization, endorsed by the European Academy of Neurology in 2017, also refute utilization of direct oral anticoagulants due to a lack of evidence. There have been nearly 10 years of experience with direct oral anticoagulants in the treatment of venous thrombosis and prevention of stroke in patients with atrial fibrillation, with purported efficacy and safety in comparison with heparins and vitamin K antagonists. Our goal is to undertake a systematic review to assess the effectiveness and safety of direct oral anticoagulants in patients with cerebral vein thrombosis to help guide clinical decision-making for patients unable to take heparins or vitamin K antagonists and to direct future studies to contribute further to an area of certain evidence-based needs.PROSPERO CRD42017078398The online version of this article (10.1186/s13643-019-1022-8) contains supplementary material, which is available to authorized users. Cerebral vein thrombosis (CVT) is a medical emergency requiring rapid treatment to prevent venous infarct, hemorrhage, and eventual neurologic disability or mortality. The incidence is estimated at 1 per 100,000 per year with mean age of 39 years, and although the mortality rate has reduced from 15 to 5% over the past 50 years due to advances in treatment and detection, morbidity rates can reach as high as 20–30% thus necessitating quick and adequate treatment [The introduction of direct oral anticoagulants (DOAC) in the early 2010s allowed for a viable alternative to VKA or heparins for treatment of venous thrombosis and to prevent stroke in patients with atrial fibrillation in both the acute and longer-term phases. The DOAC demonstrated increased utility compared with VKA by more predictable pharmacokinetics not requiring international normalized ratio (INR) testing or complicated dose adjustments, while at the same time having similar efficacy to VKA in treatment of acute venous thromboembolism (VTE), similar, if not better, rates of bleeding and mortality , 7. SubsThis systematic review will collate evidence of reported safety and efficacy of direct oral anticoagulant therapy in cerebral venous thrombosis.The eligible population includes patients of any age with a diagnosis of cerebral vein thrombosis , or computed tomographic venography (CTV)) who were treated with a direct oral anticoagulant  at any point of treatment, the acute or long-term phase. All studies with or without a comparison group are eligible for this review, including prospective trials or retrospective cohorts, case reports, or case series. No comparison group is required for studies, and reported outcomes are expected to vary in primarily retrospective or case reports, so specific outcome measures are not explicitly required for eligibility. See the “Included sources will be Cochrane Stroke Group Trials Register (last searched on February 2019), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) (1946 to February 2019), EMBASE (1947 to February 2019), and the Cochrane Central Register of Controlled Trials (1950 to February 2019). Where applicable, authors of abstracts will be contacted for further data as well as reference check for published reviews.A search strategy was developed with a research librarian. The design of this systematic review follows the PRISMA-P  and PRISTwo authors  will independently extract data capturing pertinent demographics, treatment dosage and duration, and follow-up and outcomes. For incomplete data, authors will be contacted for any possible missing data. A single reviewer (GB) will aggregate these study details into an Excel spreadsheet for analysis.Two independent reviewers will select included studies in a two-stage screening process. In stage one, two authors  screen abstracts and titles for potentially relevant articles, and in stage two, two authors  read potentially relevant articles to confirm that they met the inclusion criteria. At the end of each stage, disagreements will be resolved by a third reviewer (DD).Data items were selected based on the research objective and questions stated above. We will extract the following: general study information including date, country, language, number of patients, and type of study; participant characteristics including age, sex, medical history, medications, symptoms, and examination findings; information on CVT diagnosis including imaging modality, location of venous thrombosis, and other imaging findings such as edema or intracranial hemorrhage; and intervention details including DOAC name, dosage, and length of treatment.Outcome data will be categorized into safety and efficacy data. Safety outcome results are primary outcomes given that DOAC therapy is off-label use in CVT, so emphasis of a safety signal is the primary goal. Safety data includes occurrence of intracranial bleeding, extracranial bleeding, mortality, and any other reported adverse events. The secondary outcomes are efficacy data including recanalization time and rates, the initial and final modified Rankin Scale, and the initial and final National Institute of Health Stroke Scale score.The expected majority of articles are either case report or case series given the rarity of this disease entity and novelty of DOAC use in treating CVT, therefore two risk of bias tools will be employed for careful assessment of potential bias. The two tools include ROBINS-I  and the The purpose of this systematic review is to explore the evidence of DOAC use in CVT to assess for safety and efficacy, as well as guide protocol design for future prospective studies. The current guidelines state that DOAC use is not indicated in CVT because no high-level studies have been done as of yet; however, multiple case reports and case series have been published in the literature which have not been systematically reviewed, as well as possibly small trials. Our goal for data synthesis will be to qualitatively and descriptively present the data, and if possible, inferential statistics and meta-analysis will be performed.This systematic review will investigate the experience DOAC use in CVT, with assessment of reported safety and efficacy. The benefits of DOAC in comparison with VKA include more predictable pharmacokinetics resulting in no necessity of blood work checking of international normalized ratio (INR) and fewer interactions with other medications or foods, as well as reduced risk of intracranial hemorrhage . The popA recently reported guideline has been published by the European Stroke Organization in 2017, strongly recommended acute treatment with therapeutic heparin based on two randomized trials, however stated that there is still insufficient evidence to use DOAC in CVT based on two published case series and not by systematic review . The twoClinicalTrials.gov Identifier NCT03178864) [ClinicalTrials.gov Identifier NCT03191305) [ClinicalTrials.gov Identifier NCT03217448) [ClinicalTrials.gov Identifier NCT02913326), we aim to include the results of this study in our analysis once published [An argument to conduct prospective studies of DOAC use in CVT has been made over the past decade. Two prospective studies comparing rivaroxaban to VKA have been begun protocol development but have not yet started recruitment: “Study of Rivaroxaban for CeREbral Venous Thrombosis (SECRET)” 3178864)  and “Com3191305) . One pro8864  andublished , 19. GivPerforming a systematic review at this point is important since DOAC use in CVT is gaining attention in upcoming trials; however, due to slow recruitment, guidelines are not expected to change for some time. This review will serve to summarize available safety and efficacy evidence, as well as highlight potential bias. The review may also indicate how patient outcomes and treatment details are reported in order to assist future trial design as well as reporting of retrospective cases. If the review uncovers significant safety or efficacy concerns in the current literature, they will be flagged for prospective studies to prove or dispute such signals.Additional file 1:Search strategy. (DOCX 15 kb)Additional file 2:PRISMA-P checklist . (DOCX 2


OBJECTIVES/SPECIFIC AIMS: To provide students an opportunity to select health care-oriented course work that reflects both their interests and the increasingly diverse spectrum of health professions education and health care careers. To increase the opportunity for students to enter professional schools and health care professions with enhanced engagement and experience. METHODS/STUDY POPULATION: The 4-credit elective (Selective) curriculum is a component of the 38 credit Duke School of Medicine Master of Science in Biomedical Sciences (MBS) program which is completed over 10.5 months. Students work closely with their advisors to choose activities that reflect their interests. Selectives are offered by an array of schools, institutes, and programs within Duke University, including: the School of Medicine, School of Law, Global Health Institute, Bioethics and Science Policy Master Program, Clinical Research Training Program, Center for Documentary Studies, and Medical Informatics. Students may also pursue directed studies in areas such as health policy, or an inter-professional trip to Honduras. In addition to the course-based Selectives, three research practicum options are offered: Community Engagement, Clinical Research , and a self-selected mentored research experience. Finally, the MBS program offers 2 in-house specific Selectives: Fundamentals of Learning: Theory and Practice, and Planning for Health Professions Education. RESULTS/ANTICIPATED RESULTS: The MBS program accepted its first cohort of students in June 2015. Two cohorts have graduated and the third has begun . Our students come from diverse background with a third from populations historically underrepresented in STEM due to race/ethnicity, and another third underrepresented due to other factors such as low socioeconomic status, first generation to college, LGBQT, and those from rural and immigrant communities. Thus far, Selective distribution has been: Clinical research practicum ; Mentored research practicum ; Community engagement practicum ; Planning for health professions educations , Fundamentals of learning: Theory and Practice ; documentary film ; inter-professional trip to Honduras . Since the implementation of the curriculum, at least 53 of 70 students who have applied (76%) were admitted to health professions or other graduate schools despite having lower initial MCAT and undergraduate GPAs in aggregate than the average of students who matriculate to allopathic medical school programs: 41 to medical schools, 3 to dental school, 2 each to osteopathic and physician assistant schools and 1 each to physical therapy, business school and law school. Eighteen of the 2016 graduates, and 21 of the 2017 graduates work in research for their gap year following graduation, the majority being employed in our institution’s research programs providing a pipeline of trained research assistants and coordinators. DISCUSSION/SIGNIFICANCE OF IMPACT: Lessons learned by implementing our curriculum include the following: (1) students are eager to explore different areas of health care; (2) collaboration across schools, centers, departments, institutes, and offices increases our ability to identify common areas of interest; (3) implementing a diverse curriculum can be challenging due to the need for significant organization and planning; (4) the diversity of courses can be a source of confusion when there is a lack of standardization in learner expectations; (5) continued collaboration across, schools, centers, institutes programs, health professions and sections requires a significant amount of time and expertise. However, our programs demonstrate significant positive impacts both on students and at the institutional level. Our program shows that a diverse curriculum leads to a high number of students engaged in pursuing and successfully continuing a health profession education. Institutional benefits include a robust pipeline for a diverse research workforce.


Resilience is commonly recognized as a protective factor that increases an individual’s ability to adapt positively to adversity or change. Given the rates of change, which occur in mid and late life, understanding resilience within this population is of particular importance. Yet to date, the direct mechanisms through which resiliency functions remains underexplored in this population. As such, the current investigation seeks to examine the mechanism through which lifelong resiliency may affect the lives of older adults in order to promote successful aging. Data including assessments of lifelong resiliency , environmental mastery , instrumental activities of daily living (IADLs), mood , and subjective physical health were derived from the Survey of Midlife in the US Database (MIDUS 3). Participants were primarily White/Caucasian (88.7%) and female (54.9%); with a mean age of 63.64 years (SD=11.35). A series of hierarchical multiple linear regressions revealed that resiliency predicted better physical  and emotional health , depression ), as well as increased environmental control , and Environmental Mastery ) in models adjusted for known correlates . The present findings suggest that high levels of resilience increase not only perceptions of the world  but also direct outcomes (IADLs). Implications of the current finding include elucidation of the concept of resiliency, as well as, recommendations for increasing resiliency in late life.


In intensive cropping systems, mineral nitrogen (N) fertilizers represent the largest component of the N cycle because the indigenous N supply is not adequate. The requirement for mineral fertilizer may be reduced with the use of organic nutrient sources. A more realistic use of organic matter, particularly in sub-Saharan Africa due to limited amounts and availability, is the combined use of organic nutrient sources and mineral fertilizers. The beneficial effects of integrated use of inorganic fertilizers and organic manures on improved nutrient recoveries, soil moisture retention, cation exchange capacity, and erosion control have been reported. However, there are as many reports indicating negligible benefits or even disadvantages of combining nutrient sources on crop production. This is not surprising given the combination of organic residue sources, soils, climatic, crops, and management factors that influence nutrient dynamics. The most widely accepted function of organic materials is improving the nutrient availability to crops by supplying N. The key to both improving efficiency of N use and reducing N losses is synchronization of N supply from soil, biological N2 fixation, organic residues, and inorganic fertilizers with the crop N demand. Organic materials are not magic; N losses also result from their use. Controlling N release from organic sources depends on their nutrient content and quality, soil properties, and the environmental and management factors. This paper will synthesize the information generated from integrated nutrient management trials in sub-Saharan Africa and the Philippines. Management strategies based on an organic resources database and a dynamic soil-crop simulation model are used to identify organic sources as N fertilizers or soil amendments. The decision support tools are also used to attain optimum synchrony between release from organic sources and soils with crop N demand.


Hematological and biochemical reference intervals are an important tool for health assessment and treatment decision-making in veterinary medicine. Lack of information about reference intervals (RI) in mules force professionals to apply reference intervals developed for horses or donkeys, with the risk of misinterpretation. Thus, the aim of this study was to determine hematological and biochemical RI for healthy mules and compare them with those proposed in literature for horses, donkeys and mules. A total of 142 healthy mules (mixed breed mares × Baudet du Poitou) of both sex, all between 7 and 22 years of age and between 290 and 500 kg of live weight were sampled and 32 blood parameters analyzed in order to calculate reference intervals according to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the Clinical Laboratory Standards Institute (CLSI) standards. The values obtained for Chilean mules were within the RI in three of the 21 variables where data was available for UK donkeys and for three of 22 RI available for working horses in Pakistan; no similarities were found with those from Portuguese mules. In the case of Chilean working horses RI, mules values were within range for 11 of 25 variables. The differences found in blood biochemistry may be explained by husbandry conditions, diet, type of work and biological features. Differences between mules' reference intervals and those from donkeys and working horses highlight the importance of having specific reference values for this equid hybrid and the need to develop further research in mules under different working conditions and genetic background. Hematological and biochemical reference intervals (RIs) play a fundamental role for assessing the health condition, physiologic alterations, disease diagnosis and treatment decision-making in animals; at the same time they provide a very useful tool for animal welfare evaluations , 2. A keMules are widely used for transport of people and their supplies, especially in difficult mountainous terrains where vehicles' access is difficult or even impossible . On the n = 20 in both studies) and particular local conditions; nevertheless, they were able to observe important differences between values obtained for mules and those obtained for horses and donkeys.A considerable amount of literature has been published about horses RIs of different breeds and functions , 6, 9. ATherefore, despite the great support that mules provide as pack animals, for tourism and for equestrian sports, there is still a lack of knowledge about normal hematological and biochemical values that would allow more precise disease diagnoses and welfare assessments for these hybrids. This is why, the aim of this study was to determine hematological and biochemical reference intervals for healthy mules and compare them with those proposed in the literature for horses, donkeys, and mules.ad libitum and are kept in paddocks, only if weather conditions are adverse during winter they are housed in a loose system (barn).All measurements were taken from a reference Chilean population of mules that belongs to the army. The selection criteria proposed by Pritchard et al.  for workBlood samples were collected by jugular venipuncture during mules' resting days, using a 20 ml syringe and 21G needle. Blood was then transferred into three tubes . Samples were stored in ice in a cooler box and transported to external services for processing within the first 24 h of collection.®, Photometer 4020 (Boehringer Mannhein)], hematocrit, red blood cells (RBC) count, mean corpuscle volume (MCV), mean corpuscular hemoglobin concentration (MCHC), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, neutrophils (N), lymphocytes (L), neutrophils-lymphocytes ratio (N:L), monocytes, eosinophils, basophils, and platelets were determined (Abacus Junior Vet®). Differential leucocyte counts and erythrocyte morphology were performed on blood-stained smears using a Romanowski stain  at 1,000 × (Olympus CX31®).For hematology, hemoglobin [Cyanomethemoglobin method using Hitachi®); and glutathione peroxidase  by Ransel (Randox®). All biochemical analysis were quantified using an autoanalyzer . Plasma concentration of total protein, albumin, urea, and creatinine, were analyzed using Human kits (Human®) and lactate using Sentinel kit (Sentinel CH®). Calcium (Ca) , phosphate (P) , and Ca:P ratio was also determined.Blood biochemistry parameters included plasma activities of aspartate aminotransferase , gamma glutamyl transferase , alkaline phosphatase , lactate dehydrogenase , and creatine kinase , these were analyzed by Human kits . Blood biochemistry parameters were analyzed at the Clinical Pathology Laboratory of the Universidad Austral de Chile. Finally, cortisol was determined by radioimmunoassay at the Universidad de Concepción at the Veterinary Endocrinology Laboratory.This study was approved by the Animal Care and Use Committee of the Universidad de Chile, certificate N°19263-VET-UCH.Descriptive statistic , outlier analysis (Dixon–Reed and Tukey tests) and reference intervals (RI) were established with the software Reference Value Advisor , accordiThe individual values of each variable obtained for mules were assessed in relation to the established reference intervals published for Chilean urban working horses , workingThe ASCVP reference intervals transference method could not be applied since the laboratories did not have a data set of at least 20 healthy reference individuals for applying this validation method.n = 134), and maximum sample size was 142 (10 out of 32 variables) , anomalous results provided by the laboratory and the presence of outliers not all variables have the same sample size still all the variables remained with over 120 individuals, in accordance to the required sample size recommended by the IFCC. The variable with the minimum sample size was the N:L (riables) .Descriptive statistics, reference intervals (2.5 and 97.5 percentiles) with 90% of confidence intervals, final sample size and number of outliers for the 32 hematological and biochemical parameters are presented in n = 20)  , 11, pro0 , 11, pASVCP reference intervals guidelines recommend to validate the proposed RI with at least 20 healthy reference individuals from the laboratory's animal patient population, using the same laboratory methods for an acceptable transference comparison . HoweverThe current study found that the RI's obtained for the Chilean mule population were similar to those reported for Chilean working horses . These sThe main differences found between RI's established for Chilean mules and those for UK donkeys and Pakistani working horses were related with higher values of albumin and ALP for Chilean mules. Also, Chilean mules presented higher concentrations of urea than the UK donkeys. Serum concentration of albumin, ALP and urea could reflect the effects of diet, since working equids often have malnutrition . On the n = 20) resulting in a minor accuracy in the measure of the RI. In order to minimize this effect, the RI should be calculated by robust methods if normality cannot be established  established in this study falls within values provided for Chilean working horses, but the reference interval established for the Chilean mules was narrower and with a lower upper reference limit. This could be explained because working horses tend to have constant deprivation of their basic needs and are commonly overworked, and in consequence chronically stressed ; by contThis study provided the first comprehensive assessment of RIs for mules and identified important differences between the RIs established for mules and those established for horses and donkeys. These findings provide support of the necessity to have specific RIs for mules, highlighting the importance of using appropriate references for each population. This would allow improving clinical diagnosis and treatment decision-making for mules with different husbandry conditions and biological features.The population used in this study lives in a steppe region of Chile, has very homogeneous housing conditions, diet, genetic background and sporadic work, so caution must be taken to use this RIs with mules located in tropical and subtropical areas subjected to heavy working labors. The RIs obtained in this study will provide support to the veterinary services of the Chilean army, improving health monitoring and welfare assessment of mules. Further research is required to fully understand physiological differences between mules and other type of equids, and the influence of their biological background, husbandry conditions, environmental factors and the work performed.The datasets generated for this study are available on request to the corresponding author.The animal study was reviewed and approved by Animal care and use committee, Universidad de Chile. Certificate number 19263-VET-UCH.JL and TT conceived and designed the study. JL organized and took the blood samples, performed clinical examination, and analyzed the data. JL and TT wrote 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.


Dynamic and developmental regulation of gene expression represents an essential feature of all living cells. Kinase-mediated phosphorylation or nuclear localization of transcription factors is a well-recognized means of control of gene expression in mammals. For example, this process underlies the cellular effects of growth factors and their induction of expression of immediate/early genes as part of the “serum response” . LikewisIn cancer, dysregulation of gene expression is responsible for most of the observed cellular phenotypes, including unrestrained proliferation, resistance to cell death, metastasis, and many others . This ocHowever, translation of these insights into improved therapies for patients has been hindered by the pharmacologic challenges of targeting oncogenic transcription factors or loss of tumor suppressors. Recently, we and others have employed high-resolution functional genomic and proteomic methods to define specific molecular dependencies and biochemical activities that distinguish leukemia cells from healthy blood progenitor cells , 6. Builin vivo [Intriguingly, though the functions of MARK and SIK kinases in hematopoiesis and leukemia pathogenesis are currently undefined, these kinases share common regulatory mechanisms and signaling pathways in other tissues, such as cell metabolic and polarity signaling. It is possible that SIK and MARK signaling pathways in AML comprise a coherent mechanism of aberrant activation of MEF2C. Alternatively, they may stem from distinct modes of leukemic activation, leading to convergent and/or redundant oncogenic functions. Nonetheless, SIK and MARK knockout mice are viable, and while they have endocrine and immune defects, SIK and MARK deficiency appears to be largely compatible with normal hematopoiesis and blood development , 10. Thiin vivo . The disIn summary, these findings emphasize the importance of kinase-dependent dysregulation of transcription factor control in acute myeloid leukemia, substantiating its clinical investigation for improved diagnosis and therapy. This work also highlights the opportunities for biological discovery afforded by the use of improved functional genomic and proteomic methods. We anticipate that future integration of these technologies will yield important insights into the molecular mechanisms of cancer pathogenesis, including the definition of additional mechanisms of gene control and dysregulation in human cancer. In particular, it is possible that elucidation of additional enzymatic regulators of transcription factor functions by way of acetylation, methylation and other post-translational modifications will yield new pharmacologic strategies to target ‘undruggable’ targets such as MYC and numerous other oncogenic proteins in human cancer.


We examine the association between the quality of family planning (FP) counseling received in past 24 months, and current modern contraceptive use, initiation, and continuation, among a sample of women in rural Uttar Pradesh, India.N = 1398). We measured quality of FP counseling using four items on whether women were informed of advantages and disadvantages of different methods, were told of method(s) that are appropriate for them, whether their questions were answered, and whether they perceived the counseling to be helpful. Positive responses to every item was categorized as higher quality counseling, vs lower quality counseling for positive response to less than four items. Outcome variables included modern contraceptive use during the second round of survey, and a variable categorizing women based on their contraceptive use behavior during the two rounds: continued-users, new-users, discontinued-users, and non-users.This study included data from a longitudinal study with two rounds of representative household survey (2014 and 2016), with currently married women of age 15–49 years; the analysis excluded women who were already using a permanent method of contraceptive during the first round of survey and who reported discontinuation because they wanted to be pregnant , and those who received higher quality FP counseling at 4.14x the odds of reporting modern contraceptive use (95% CI: 1.72–9.99), as compared to women reporting no FP counseling. Women receiving higher-quality counseling also had higher likelihood of continued use , as well as new use or initiation  of modern contraceptives. Receipt of lower-quality counseling also showed statistically significant associations with continued and new use of modern contraceptives, but the effect sizes were smaller than those for higher-quality counseling.Findings suggest the value of FP counseling. With a patient-centered approach to counseling, continued use of modern contraceptives can be supported among married women of reproductive age. Unfortunately, FP counseling, particularly higher-quality FP counseling remains rare. Providing high quality family planning (FP) counseling is important to support modern contraceptive use that meet couple’s needs. Improving the use of modern contraceptives in turn has potential to reduce unintended pregnancy and short inter-pregnancy intervals which lead to adverse health consequences for mothers and infants. We examined the association between quality of FP counseling received in the past 24 months and modern contraceptive use, initiation, and continuation among married women who were not already using any permanent method of contraceptive, and who did not report discontinuation because they wanted to become pregnant, in rural Uttar Pradesh, India. We measured quality of FP counseling using four items - whether the woman was informed of advantages and disadvantages of different methods, was told of method(s) appropriate for her, whether her questions were answered, and whether she perceived the counseling to be helpful. Positive responses to every item was categorized as higher quality counseling, vs lower quality counseling for positive responses to less than four items. The minority of participants had received any FP counseling (22%); only 4% received higher-quality counseling. Those who received any FP counseling  had higher odds of reporting current use of any modern contraceptive, as compared to women reporting no FP counseling. Similar associations were observed with initiation and continuation of modern contraceptives. Findings suggest the value of quality FP counseling. With FP counseling, continued use of modern contraceptives can be promoted among married women of reproductive age.Half of the currently married women aged 15–49 years in India use modern contraceptives, with 70% of all users choosing female sterilization , 3.In response to this low prevalence of contraceptive use in India, recent efforts have tried to address barriers to access, with strategies to strengthen quality of family planning counseling provided . GloballDespite the early and ongoing global work on quality of FP counseling services, few studies in low and middle-income countries (LMICs) such as India have tried to empirically assess quality of FP counseling –26 and iWe used data from a longitudinal household survey conducted across 49 districts of UP, India. We used a multistage sampling design to obtain a representative sample of currently married women in the reproductive age (15–49 years), also described elsewhere . A censun = 31 women), women who were already sterilized at baseline (n = 329 women), women whose husbands were already sterilized at baseline (n = 13 women), and women who reported discontinuation of contraceptive use because they wanted to become pregnant (n = 30 women). We decided to exclude women who reported a desire to become pregnant, in order to examine the effects of FP counseling among women who have a potential need for contraceptives. We thus had a total sample of 1398 women for analysis. We weighted the data based on the sampling design to produce estimates representative of the selected geographies.Since the analysis focused on initiation and continuation of modern contraceptives during the two rounds of survey, we excluded four groups of women from the analysis: women who were more than 49 years of age at the second round of survey  and the Health Ministry Screening Committee Indian Council for Medical Research.mCP, which assessed use of any modern method of contraceptive reported at the second round of the survey. For the second analysis assessing the relationship between FP counseling, and initiation and continuation of modern contraceptive, our main outcome assessed method use behavior during the two rounds of survey. We categorized women as: a) Continued users- women who were using any modern contraceptive method during both the survey rounds b) New users- women who were not using any modern method during the first round but were using one during the second round of survey, c) Discontinued users- women who discontinued using any modern method from first to second round and d) Non-users- women who were not using any modern contraceptive method in either survey round. Modern contraceptive methods used by the eligible sample of women included Oral Contraceptive Pill, IUD (including PPIUD), injectable, implants, male and female condoms, lactational amenorrhea method, diaphragm and emergency contraceptive pill.The survey tools used in this study were based on formative research and expert input, and were pilot tested prior to implementation. For the first analysis examining the relationship between FP counseling and modern contraceptive use, our main outcome of interest was quality of FP counseling, which assessed any experience with FP counseling during the 2 years between the two rounds of survey. The variable was categorized as: a) No counseling, b) Receipt of lower quality counseling and c) Receipt of higher quality counseling. No counseling was defined by answering no to the question, ‘In the last 2 years, did you receive any counseling / advice on FP from any community health worker, or health provider at a health facility?’ Among those who reported to have received any counseling based on the above question, the following four yes/no questions were used to capture quality of the counseling received:Were you given information about the FP methods available, including the advantages and disadvantages of the methods?Did the health service provider exchange information with you about which FP method(s) would be most appropriate for you?Would you say the health service provider was able to address all your/your husband’s questions?Would you say the counseling helped you in choosing the right method for you?The key independent variable was higher quality counseling, vs lower quality counseling for a positive response to less than four items. Existing literature guided the development of the measure for quality of counseling, consistent with the framework of rights-based approach to counseling by Bruce  in India. This is reflective of the programmatic focus on task sharing for care in India, with the implementation of national-level interventions which have designated ASHAs to carry out doorstep FP counseling and delivery of contraceptives . FindingA strength of our study is its longitudinal design, which allows for an exploration of method switching and assessment of temporal relationships. Among those not using any permanent methods, the most prevalent method of modern contraception used were condoms, followed by oral contraceptive pills. The discontinuation rates were, however, high for both the methods. This is consistent with prior studies in India which have indicated frequent discontinuation of these short-acting methods . LARC meAlthough this current study provides important insights into the effect of quality of FP counseling on contraceptive initiation and continuation, there are a few limitations. First, the study is susceptible to the presence of recall bias and social desirability bias due to use of interviewer-administered questionnaires and self-reported measures for contraceptive use and counseling. Alternative methods to measure quality of FP care such as exit interviews, counseling session observations, or using mystery clients couple help triangulate and substantiate findings from traditional measures . Second,Findings from the study highlight the value of FP counseling to support increased modern contraceptive use and reduce discontinuation in a context such as UP, India where contraceptive use remains low. With high quality and a person-centered approach to counseling, continued use of modern contraceptives can be supported among married women of reproductive age. Unfortunately, FP counseling, particularly higher quality FP counseling, remains rare in UP. These findings highlight the importance of access to, and delivery of, quality FP counseling via highly trained CHWs and clinical providers.


Benthic—pelagic coupling plays a pivotal role in aquatic ecosystems but the effects of fishery driven interactions on its functioning has been largely overlooked. Disentangling the benthic—pelagic links including effects of mixed fisheries, however, needs sketching a whole description of ecosystem interactions using quantitative tools. A holistic food web model has been here developed in order to understand the interplay between the benthic-pelagic coupling and mixed fisheries in a Mediterranean system such as the Strait of Sicily. The reconstruction of the food web required review and integration of a vast set of local and regional biological information from bacteria to large pelagic species that were aggregated into 72 functional groups. Fisheries were described by 18 fleet segments resulting from combination of fishing gears and fishing vessel size. The input-output analysis on the food web of energy pathways allowed identifying effects of biological and fishery components. Results showed that the structure of the Strait of Sicily food web is complex. Similarly to other Mediterranean areas, the food web of the Strait of Sicily encompasses 4.5 trophic levels (TLs) with the highest TLs reached by bluefin tuna, swordfish and large hake and largely impacted by bottom trawling and large longline. Importantly, benthic-pelagic coupling is affected by direct and indirect impacts among groups of species, fleets and fleets-species through the whole trophic spectrum of the food web. Moreover, functional groups able to move on large spatial scales or life history of which is spent between shelf and slope domains play a key role in linking subsystems together and mediate interactions in the Mediterranean mixed fisheries. Fishing activities targeting benthic and demersal organisms are usually considered unrelated to those targeting pelagic species, and independently managed. In fact, benthic and pelagic domains have been often treated as separate subsystems. However they are not, because of physical ,2 and biThe release of fecal pellets in the pelagic domains sinking to deeper domains, the occurrence of “marine snow”, the re-suspension of organic material sunk on the bottom –9 are exFishing is among the most worrisome stressor to BPC across short temporal scales ,18 and tThe effects of fishing on the functioning of BPC in an ecosystem context, which is a crucial aspect in the Ecosystem-Based Fishery Management (EBFM) , has beeBased on a standard food web ECOPATH model, this paper presents a novel application to the Strait of Sicily (SoS) ecosystem specifically developed for studying the BPC in the Mediterranean Sea. The SoS hosts one of the largest Mediterranean bottom trawl fisheries in terms of fleets, landings and economical incomes  and, at The study area of the food web model coincides with the northern side of the Strait of Sicily, which stretches off the southern Sicily coast and is characterized in its central portion by a narrow continental shelf that separates two wider portions of shelf coinciding with the Adventure Bank in the west and the Malta Bank in the east . The stuhttp://www.ecopath.org) [2 at depths ranging between 10 and 800 m, excluding non-trawlable area represented by zones interdicted to fishing, zones deeper than 800 m and hard/rocky substrates  . In partath.org) ) and bribstrates . The modThe model development required access, review and analysis of data in the SoS for approximately 1400 taxa. Species-specific parameters and dietary data were compiled mainly from publicly available, published and unpublished information, as detailed in -2), by considering species-specific catchabilities. Since the catchability of MEDITS trawl surveys has been seldom studied and is not available for the SoS, we used specific catchability terms derived by the comparison of MEDITS data with independent stock assessments [Sardina pilchardus and anchovy Engraulis encrasicolus, experimental acoustic surveys carried out in the SoS were taken into account [Fishery-independent biomass density estimates encompassing demersal fishes, cephalopods and other invertebrates were obtained from bottom trawl surveys carried out in spring 2004 and 2005 in the model area within the MEDITS program  . MEDITS essments  and withessments  (Tyrrhenessments  (Adriatiessments ) provideessments ) wheneve account ,56. The  account  . Data were aggregated by 18 fleet segments resulting from a combination of fishing gears  and 3 vessel size classes based on the length overall (LOA): class 1, LOA <12m; class 2, LOA 12-24m; class 3, LOA >24m, bottom otter trawl were also distinguished into categories according to main target species (Parapenaeus longirostris and giant red shrimp Aristaeomorpha foliacea) span over a space larger than the model area [Fishery landings by species and gear in the SoS during 2005 were drawn from the national monitoring of commercial fleets within the European Data Collection Regulation  were based on a first assessment of diet similarities and life history parameters of involved species using multivariate analysis techniques in order to cluster species with similar diets, growth and mortality rate. FGs definitions were then refined on the basis of expert opinion in order to better describe ecological and fishing features of the SoS. Commercially important species were considered as single FGs, with the red mullet and the European hake represented in 4 and 5 size classes, respectively. Moreover, several FGs were split into shelf and slope components and each group labeled as benthic, demersal or pelagic  in orderBiomass and catches (landings plus discards) by FG were obtained by summing over the species belonging to each group. Other input parameters  and diet data for each FG were obtained as a weighted average of the values for the species in that group , with thThe basic features of the food web were defined by ecological indices such as Trophic Level (TL), Primary production on Respiration (PP/R) and Primary Production on Biomass (PP/B). The Omnivory Index (OI) and the System Omnivory Index (SOI) were calculated to quantify the width of the trophic spectrum for each FG and as a measure of food web complexity and interconnection, respectively .In order to evaluate the role of all food web components on the BPC we calculated fluxes and impacts among FGs, among fleets and between FGs and fleets. The fluxes are a direct output of the model and were used to determine the strength of direct interactions  among FGs and across the three domains considered . Direct fishing effects were quantified by i) the exploitation rate E  for each FG belonging to a certain domain, and ii) the cumulative exploitation rate (CumE) for any fleet segment. CumE was calculated (1) in order to compare exploitation across fleets and consequently to visualize which domain was more impacted.i) produced by a component  i on the whole food web [i.The application of the input-output analysis on the web of flows i.e., the Mixed Trophic Impact analysis (MTI)  allowed food web , while tdemersal on FGs_benthic and pelagic). Finally, we explored the overall effects of fisheries across FGs and fleet segments respectively and the main cascades relevant for BPC.Therefore, in order to assess the impact of each FG on BPC, we calculated the portion of cumulative overall impact both positive and negative of a FG on the FGs belonging to the other domains  to those from stock assessment and other sources (Aristaeomorpha foliacea (i) and Engraulis encrasicolus (g) the differences in the areas to which stock assessments and Ecopath refer might explain the discrepancies in the biomasses. Higher catches of red mullet in Ecopath than in assessment models could be instead attributed to higher discards represented in the former. Ecopath mortality rates . Nevertheless, the comparison highlighted that the integration of data provided by Ecopath results in a general underestimation of fishing mortalities and overestimation of natural mortalities with respect to stock assessments. Globally, variables and parameters used in our model resulted reconciled.Biomass and catches used in the Ecopath model resulted highly correlated  and consumption (1599 t km-2 year-1) to the total flows in the system . Total respiratory and detritus flows corresponded to 962 and 967 t km-2 year-1, respectively.According to the model, the food web of the Strait of Sicily encompasses 4.5 trophic levels TLs, . The higGlobally, FGs resulted well interconnected as shown by SOI = 0.30 and by the fact that more than 50% of total consumer FGs showed a relatively high variability of feeding across trophic levels (OI>0.3).-2 years-1) was exchanged by lower “taxonomic” groups  across the benthic and pelagic domains , contributed to a less extent to the consumption fluxes linked to BPC , large red mullet (MUL3) and large pelagic fishes (LPL) also suffered high exploitation rates , macrobenthos carnivore (C), omnivore (O), scavenger (SCA) and detritus feeder (DF); in the demersal domain, high ɛi values were shown by demersal fish from slope (DFS), TRA, MSC, rays from shelf (RSH), sharks from slope (SSS) and decapods natant from the slope (DNS). Finally in the pelagic domain, large pelagic fish (LPL), euphausiids (EUP), European anchovy (ENG), zooplankton medium (ZM) and small (ZS) were the groups with highest ɛi  had negative direct impact on main target demersal species such as large European hake (HAK3 and 4), red mullet (MUL3), rays and sharks (RSH and RSS), but had positive effects on hake and red mullet juvenile . Moreover, these fisheries had negative indirect impact on benthic organisms such as benthic decapods  mediated by the depletion of their predators . SimilarThe MTI disentangled by fleet  shows thBoops boops) and MSG (mainly Schedophilus medusophagus) and a decrease in jellyfish (ZG). At the same time, biomass of predators such as benthic cephalopods from slope (CEBS), mesopelagic piscivorous fish (MSP) and DFS is released. However, forage fish and horse mackerel populations can increase so that predators such as European hake could benefit from this food resource  and, general issues encountered when working in a context of multiple targets and mixed fisheries, such as the difficulties in defining a model area that overlap completely resources, exploitations and data available.The food web of the Strait of Sicily described by our model resulted quite complex as suggested by the System Omnivory Index (SOI = 0.30), which is way above the average of 105 food web models  and otheThe results have evidenced that most of the food web energetic fluxes were exchanged between bacteria and the various type of detritus  and then, transferred from the detritus to the upper trophic levels. Bacteria and invertebrates of benthic and pelagic domains are characterized by high rate of production and consumption so that they handled the bulk of fluxes directly and indirectly linked to detritus. Thus, through a variety of feeding strategies, they were able to efficiently use detritus allowing an important coupling between planktonic and benthic invertebrates. Accordingly, other authors have suggested a prominent role of particulate organic matter, especially for marine snow (here SPOM)  across tTrachurus spp. (TRA), rays, sharks, cephalopods and demersal fish (DFH) had high ranks of overall effects. Medium pelagic (MPL), demersal piscivores (DSP) and reptant decapods from shelf (DRH) have high MTI values and fish that undergo through size/age related diet shifts (here red mullet and European hake) interact with a large number of prey and predators from all domains deeply contributing to BPC in space [Moreveor, we have shown that high and medium trophic level items such as large pelagic fish (LPL), mesopelagic fish , in space . Most ofin space ,79 makinin space ,80. Morein space  because in space .The SoS has been an important fishing ground since ancient times and, at the same time it represents an ecosystem that largely contributes to Mediterranean biodiversity in terms of habitats and species . CriticaOur results show that fishery driven interactions are involved in BPC through their pervasive action on the whole food web and through indirect effects among fleets. Acting on resources linked by weak interactions, the fleets possibly promote cascade effects such as those shown here for the Strait of Sicily but possibly observable in other Mediterranean ecosystems.Isidella elongata and Funiculina quadrangularis are critically endangered by trawlers in the SoS [The model proposed in this study does not include processes and effects linked to the habitat modification caused by bottom trawling as well as the effects of physical factors  and the mass balance can facilitate the identification of main contributors, but their consistency may be strengthened in a next step by implementing the temporal dynamic approach i.e., the Ecosim module ,85. Howe the SoS .Benthic-pelagic coupling therefore appears to be shaped by multiple interactions among group of species (sp.-sp.), among fleets (fleet-fleet) as well as between fleet and group of species (fleet-sp.). Although the analysis of direct interactions suggests that main elements of BPC are mediated by wasp-waist groups , which show great contribution to energy transfer as consumers and sources in the food web, the quantification of direct and indirect impacts highlighted the important role of other components in the BPC.Interestingly, it has been recently suggested that the increasing depletion of top predators over the past decades, has led to a shift of fisheries towards forage fish and benthic invertebrates  that couMoreover, the result of this study shows that BPC mediates the Mediterranean mixed fishery through an intricate combination of biological and fisheries interactions and therefore the idea of unrelated demersal and pelagic fisheries is to be set aside.Overall, this study provides a novel and comprehensive quantitative integration of a large amount of information on biomass density, population dynamics and trophic interactions in the Strait of Sicily, contributing to a deeper understanding of the functioning of the whole food web, and offers a novel assessment of the overall effects of fishing in an ecological Mediterranean framework.S1 Appendix(DOCX)Click here for additional data file.S1 TableB); diet information used to build the diet matrix; production per unit of biomass (P/B); consumption per unit of biomass (Q/B). F = fishing mortality, M = natural mortality, Z = total mortality.Biomass ((DOCX)Click here for additional data file.S2 Table−2), production/biomass ratio , consumption/biomass ratio ; Landing and Discards are expressed in t km−2 year−1. Outputs: trophic level (TL), ecotrophic efficiency , production/consumption (P/Q), respiration/assimilation (R/A), omnivory index (OI). Dom = Domain: p = pelagic, d = demersal, b = benthic.For each functional group (FG) are detailed inputs: biomass Click here for additional data file.S3 TableRaw data across functional groups of predators in columns and preys in rows.(DOCX)Click here for additional data file.S4 TableB total biomass (exluding detritus), Q total consumption, Ex sum of all exports, R sum of all respiratory flow, FD sum of all flows into detritus, P sum of all productions, TST total system throughput, PP net primary production, TE mean transfer efficiency, C capacity, O overhead, A ascendency, FCI model stress, Y catches, TLm mean trophic level of catches, Y/PP gross efficiency.(DOCX)Click here for additional data file.S1 FigProportion of preys (rows) in the diet of the predators (columns) in ranks. Fraction of import in the diet (fraction of energy assumed to be taken out of the system) are also indicated.(TIF)Click here for additional data file.S2 FigRows are impacting FGs and columns impacted FGs.(TIF)Click here for additional data file.


Pharmacogenomics suggests that diseases with similar symptomatic presentations often have varying genetic causes, affecting an individual patient’s response to a specific therapeutic strategy. Gene therapies and somatic cell therapies offer unique therapeutic pathways for ocular diseases and often depend on increased understanding of the genotype-phenotype relationship in disease presentation and progression. While demand for personalized medicine is increasing and the required molecular tools are available, its adoption within pediatric ophthalmology remains to be maximized in the postgenomic era.The objective of our study was to address the individual hurdles encountered in the field of genomic-related clinical trials and facilitate the uptake of personalized medicine, we propose to conduct a review that will examine and identify the digital technologies used to facilitate data analysis in somatic and gene therapy trials in pediatric patients with ocular diseases.This paper aims to present an outline for Healthcare Information Technology and Information and Communication Technology resources used in somatic and gene therapy clinical trials in children with ocular diseases. This review will enable authors to identify challenges and provide recommendations, facilitating the uptake of genetic and somatic therapies as therapeutic tools in pediatric ophthalmology. The review will also determine whether conducting a systematic review will be beneficial.Database searches will be initiated in September 2018. We expect to complete the review in December 2019.Based on review findings, the authors will summarize methods used for facilitating IT integration in personalized medicine. Additionally, it will identify further research gaps and determine whether conducting further reviews will be beneficial.PRR1-10.2196/10705 By matcHIT and ICT have tremendous potential to contribute to and enhance patient-centered approaches . Electroin vitro, have clear translational value [ex vivo before delivering them to the patients [Recent advances in scientific technology, including facile genome sequencing, advanced genome editing techniques, and controlled isolation and differentiation of cells al value . In addial value , enablinal value . Therapial value ; here weal value . Gene thal value . “Correcal value , for exapatients . As inhepatients .New technologies in health care are allowing physicians to tailor and customize treatments to individual patients, translating genomic research into medical practice. Acting as a driving force, novel technologies are central to the advancement of gene and somatic therapy trials. As there is no existing synthesis of the electronic processes used in somatic and gene therapy trials in pediatric patients with ocular diseases, this gap will be addressed by the proposed review.We will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol PRISMA-P 2015 Checklist  and the Systematic scoping reviews intend to promptly gather and provide evidence on essential concepts pertaining to broad research subjects . As oppoAlthough scoping reviews do not require a strict methodological approach, methodological frameworks have been developed by Arksey and O’Malley in 2005 and by Levac, Colquhoun, and O’Brien in 2010 ,27.Following preliminary and exploratory reading on somatic and gene therapy trials involving pediatric patients with ophthalmic conditions, no synthesis of evidence around the technological advances used in these trials was found, demonstrating a research gap. In light of this evidence paucity, we formulated the following research question: What are the range of health care information and communication technologies applied to achieve patient-centered care in children undergoing somatic and gene therapies for ocular diseases?We will systematically searche MEDLINE/PubMed, Embase, and Scopus through the Imperial College London library. Subsequent to the identification of MeSH, subject headings, and keywords, the medical librarian at Imperial College London will be asked to review the search strategy. Search terms will consist of MeSH and keywords linked to (1) pediatric population; (2) digital technologies; (3) traditional care; and (4) outcomes. No restrictions will be applied on publication date, publication status, or study location. Subsequent to the MEDLINE/PubMed search, the search strategy will be converted to Embase and Scopus searches. The search strategy may be requested from the first author once finalized. Following database searches, results will be imported to EndNote, a reference software. Once the included studies are determined, we will thoroughly search their bibliographic citations to identify supplemental relevant studies.The following Population, Intervention, Comparator, and Outcome framework was developed for the purpose of the review’s research question.Eligible studies will consist of pediatric patients with ocular diseases undergoing somatic and gene therapy trials.Interventions will consist of advances in health care technologies, including, eHealth, mobile health, big data, and real-world data utilized in genomic and somatic therapies in children with ocular diseases.No comparisons will be made.Treatment and process outcomes will be assessed. Treatment outcomes will consist of clinical effectiveness, clinical efficacy, and patient-relevant outcomes. Process outcomes will evaluate the quality and accessibility of technological advances.The following studies will be included (1) No restrictions will be placed on study type; (2) English publications; (3) publications obtained from MEDLINE/PubMed, Embase, and Scopus; and (4) publications focusing on digital technologies used in pediatric somatic and gene therapy clinical trials.We excluded non-English publications.EndNote X8.2  will be used for the collection of bibliographic references. Following the assemblage of references following database searches, duplicates will be removed using a deduplication tool on the bibliographic software. Where duplicates are not removed automatically by means of the EndNote software, reviewers will examine and compare findings thoroughly. Upon agreement, duplicates will be removed. Authors of included studies will be contacted if required.In the first phase of the selection process, 2 reviewers will independently perform screening of titles and abstracts. Following elimination of papers with discernible ineligibility, eligibility of the remaining papers will be assessed in the second phase of the study selection process through full-text reading. Disagreements on study eligibility will be resolved through discussion between reviewers. If no consensus is reached, a third reviewer will assist in the selection process. In the final phase of the selection process, bibliographic references of included studies will be reviewed, thereby identifying additional potentially relevant papers. A PRISMA flow diagram will be used to illustrate the selection process, as well as exclusion reasons, demonstrating the review’s transparency and replicability.We will extract data from included studies and compile onto data extraction forms designed by the research team. Prior to comparison of completed data extraction forms, data will be extracted independently by 2 reviewers. Differences in opinions will be resolved through discussion and, if required, assistance of a third reviewer. A single form consisting of the required data will be generated.Data extracted from included studies will consist of the following information: (1) paper specifications; (2) study characteristics; (3) participant characteristics; (4) intervention details; (5) comparator details; and (6) outcome measures. Details pertaining to extracted data may be found in The methodological quality of included studies will be assessed by 2 independent reviewers. If, following discussion, reviewers cannot reach consensus on the risk of bias pertaining to included studies, a third reviewer will be asked to aid in decision making.To assess the methodological quality of included studies, the Cochrane Collaboration Risk of Bias Tool will be applied. The following 6 criteria will be evaluated in each included study: (1) random sequence generation (selection bias); (2) allocation concealment (selection bias); (3) blinding (performance bias and detection bias); (4) incomplete outcome data (attrition bias); (5) selective reporting (reporting bias); and (6) other bias.Following criteria assessment, risk of bias of included studies will be determined, and studies will be judged as “high risk,” “low risk,” or “unclear risk.” To illustrate the methodological quality of the review’s included studies, a Risk of Bias Graph and a Risk of Bias Summary will be presented.Subsequent to data extraction, results will first be synthesized numerically or by means of a descriptive statistic. Providing an overview of the quantity and type of included papers, the descriptive analysis will consist of the following information: (1) intervention type, control group, sample size; (2) characteristics of the population involved including, age, gender, ocular disease targeted, location; and (3) intervention outcomes including, health treatment and process outcomesResults will also be synthesized narratively. Using the PRISMA-P 2015 Checklist, data will be presented in a tabular format to supplement the narrative synthesis. This will consist of a synthesis of all included papers that will enable guidance and allow assessment of potential heterogeneity between included studies. To ensure the reliability of our findings, narrative synthesis reporting will be conducted in a transparent manner.Providing a holistic analysis of the intervention, the quality of the studied intervention will be determined by evaluating through outcome measures, as well as satisfaction of health care professionals and patients and the complexity of the intervention. Recommendations regarding future research, policy, and practice will be developed by the authors. Details of this stage are currently being developed by the research team and may be subjected to iterations or further updates following review commencement. We intend to finalize this stage in December 2017.Database searches will be initiated in September 2018. We expect to complete the review in December 2019.The review intends to provide evidence on technology applied to genetic and somatic cell therapy trials in children with ocular diseases. In addition to developing recommendations that will enable collaboration between key stakeholders, we aim to provide a comprehensive overview that will facilitate decision making and improve pediatric health care. Thus, we aspire to move evidence into practice, or translate research into medical practice, through the circulation of our review findings. We predict that the review will also provide insight to other researchers as additional research gaps that may need to be addressed will be identified by means of evidence gathered in the proposed review.Responding to a research gap, the review will provide evidence on technological advances related to somatic and gene therapy trials in children. We will perform rigorous and systematic search of multiple health and medicine databases. No restrictions applied on publication date, status, or location. The review will identify unmet needs of pediatric patients with ophthalmologic disorders, thereby informing policy makers and donors. On completion of the review, additional research gaps will be identified, thereby guiding the conduct of future systematic reviews. Review findings will enhance the management of pediatric patients undergoing somatic and gene therapies by identifying digital technologies that improve patient safety, engagement, and satisfaction. The effectiveness of digital technologies on treatment outcomes will be assessed.Language restrictions will be imposed (non-English papers will be excluded). As the review will outline the existing electronic processes applied in somatic and gene therapy trials for children, quality appraisal will not be conducted on identified papers.We believe consulting experts will provide valuable insight regarding the development of recommendations, challenges that need to be addressed, and potential solutions. In addition to consulting pediatric somatic and gene therapy experts and researchers, regulatory authorities and eHealth experts at Imperial College London, the University of Oxford, and Stanford University will be consulted throughout the conduction of the review. This will allow the reviewers to obtain guidance that has not been provided in the searched literature. Their feedback on the protocol and review findings will be requested prior to completion of the final report. Through multiple consultations, we intend to engage subject experts in the development and design of the systematic review in addition to the subsequent action plan. It is intended that by means of various consultations, we will develop strategies facilitating the uptake of novel technological advancements by researchers, health care practitioners, and patients in the field of personalized medicine.The review intends to provide evidence on the digital technologies used in data analysis and interpretation in pediatric somatic and gene therapy trials. The review intends to develop and circulate strategies to promote their uptake, enhance patient safety and enhance development of personalized medicine within health care systems. In order to enable informed decision-making skills of consumers and improve health care quality and access, results will be actively communicated to health care providers, patients, and other relevant stakeholders. To ensure transparency, replicability, and applicability of the proposed systematic review, we intend to distribute our work from the initial stage (protocol) to the final product.Genomics is reshaping health systems. While advancements in technologies are enabling the personalization and customization of care, there is paucity around the evidence of their utilization and impact in somatic and gene therapy trials in children. As eHealth and mobile health resources have the potential to empower patients through enhancement of decision-making skills and patient engagement, the review intends to exhibit how their utilizations may be maximized in pediatric somatic and gene therapy trials to improve the quality of pediatric ophthalmology.


Social Convoy Theory is well established in the gerontology literature and provides a framework for understanding the relationships of individuals in a group of people with whom they give and receive social support over the life-cycle. Previous research substantiates a link between the importance of social convoys and health outcomes among older adults with advanced illness. However, the concept of social convoy has not been applied to mobile health  for palliative care. Often mHealth systems are designed for individual users, lacking innovative solutions for multiple, age-diverse, simultaneous users to maximize benefit. Therefore, the Social Convoy Palliative Care  mobile application (K76AG059934) was developed using a rigorous iterative process with older patients, their social convoy, and health providers, to foster effective integration of the social convoy in palliative care-specific mHealth. Based on these findings, this presentation discusses strategies to design mHealth for a convoy of users in geriatric palliative care.


The ever growing environmental pollution has stimulated the rapid development of environmental catalysis in recent years. Environmental catalysis is a multidisciplinary research field for which more and more chemists, materials scientists, as well as environmentalists have devoted their efforts working in this field because of the bright potentials in improving human health and life quality. With the progresses in controllable materials synthesis, advanced characterizations , high-level analytical chemistry, together with the computational studies, catalysis continues to be the driving force for generation of clean energy, abatement of major pollutants in air and water, and meantime the theories behind the catalytic reactions are illustrated. In the current Research Topic, an elegant collection of original research and review articles reporting the synthesis of high-performance catalysts, their applications in various catalytic technologies for environment remediation, and relevant theoretical calculations for understanding the catalytic mechanisms is presented.2, several routes including creating defects and element doping are developed Qin and Lin et al., introduced carbon and nitrogen elementals into TiO2 simultaneously and demonstrated the improved catalytic property of such C, N-TiO2 catalyst compared to anatase TiO2 under simulated sunlight irradiation for degradation of 4-nitrophenol. Moreover, they also evaluated the embryonic toxicity of intermediate degradation compounds . Silva et al., synthesized Pd-Cu loaded over hybrid materials of carbon nanotubes and TiO2 for nitrate reduction. It reported that the Pd-Cu loaded on the hybrid materials have high photocatalytic performance for Silva et al.). Other than TiO2, the bismuth compounds as a new class of photocatalytic materials have been paid much attention in recently. Among them, bismuth oxychloxide (BiOCl) exhibits excellent photocatalysis behaviors driven by UV light. To expand its light absorption to visible light spectrum, efforts to fabricate graphene oxide/BiOCl nanocomposite film and BiOI/BiOCl film are reported by Zhu and Zhang et al., respectively . BiVO4 is found to be a visible light-activated photocatalyst due to the narrower band gap than TiO2, the involvement of graphene oxide or BiOI can further improve the photocatalytic performance for RhB degradation. However, the poor specific surface area limits its catalytic performance. To this end, Channei et al. utilized a co-precipitation method to coat SiO2 onto BiVO4 and obtained SiO2/BiVO4 composites with larger surface area and higher photocatalytic activity and degradation efficiency towards methylene blue dye with respect to monoclinic BiVO4 . Furthermore, a comprehensive overview on semiconductors loaded with carbon cocatalysts as photocatalysts for water splitting and pollutant degradation was provided by Peng et al., aiming to give a clue to the rational design of low-cost photocatalysts with more efficient solar light utilization. The synthesis methods of various types of carbon-semiconductor composite photocatalysts were summarized, the contribution of different carbon allotropes like C60, carbon nanotubes, graphene to the enhanced photocatalytic activity were compared and the cocatalytic effect mechanisms were discussed .Photocatalysis remains to be a research focus for the environmental catalysis community due to the wide applications in carbon dioxide reduction, oxidation of volatile organic compounds (VOCs), elimination of aqueous organic pollutants and disinfection, water splitting .Catalytic conversion of biomass to biofuels is another emerging topic in the environmental catalysis field out of the urge to transform the agricultural wastes into resources and to reduce the carbon dioxide emission from fossil fuels combustion . Owing to the rise of supercomputers, computational studies become important complementary tools for elucidation of the inherent mechanisms of catalytic reactions. Currently Ab initio techniques like Density Functional Theory (DFT) are popularly adopted for theoretical calculations. Here in this Research Topic, two examples of DFT studies on the mechanisms of CO oxidation catalyzed by Mn-embedded divacancy graphene and boosted oxygen reduction reaction performance catalyzed by two-dimensional metal–organic frameworks TM3(hexaiminotriphenylene)2 monolayer  were shown .Pharmaceutical and personal care products (PPCPs) are emerging contaminants, which are widely present in pharmaceutical and hospital wastewater, even natural water. In this Research Topic, Fe-MCM-41s were fabricated at different conditions to adsorb widely used antibiotics ciprofloxacin hydrochloride (CPX) for its removal from waste water (We believe that this collection, Environmental Catalysis and the Corresponding Catalytic Mechanism, illustrates the advancements of catalysis for environment remediation and innovations in clean energy with diminished production of undesired by-products. At the same time, challenges and perspectives for this field are also addressed with the hope that future interests will be focused to help establish a world with clean air and water, as well as sustainable and green energy for human to live in.ZA drafted the manuscript. HS and AF made substantial improvements, and all authors approved for publication.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.


In January 2018, Congress passed the Recognize, Assist, Include, Support, and Engage (RAISE) Family Caregivers Act to establish a national strategy to acknowledge and assist family caregivers. The success of such an effort will be contingent on knowledge and dissemination of best practices. We conducted a policy project funded by the Milbank Memorial Fund that profiles five geographically and politically diverse states that have pursued novel approaches to supporting family and unpaid caregivers of older adults. We discuss findings from national and state reports, state aging plans, and interviews with 26 key informants. We find that each state  sought to strengthen supports for family caregivers as an element of broader community-based long-term services and supports strategies. Supports for family caregivers included financial support for working caregivers, caregiver assessment and care planning, and expanded access to respite care: several states included these services within programs targeted to persons at high risk of institutionalization or Medicaid-entry. Key informants noted the importance of tailoring programs to suit each state’s unique demographic, geographic, and service delivery context, and reported that individual stories, advocacy, and data were critical to placing family caregiving on legislative policy agendas. State leaders highlighted the pivotal role of state aging networks in efforts to supporting caregivers, given these entities’ deep knowledge of local community needs and challenges and established relationships with local service providers. Meaningful change often required a long-term commitment and sustained incrementalism, typically by innovating on a smaller scale before expanding statewide.


Responding to Zika virus infections in Houston, Texas, USA, presented numerous challenges across the health system. As the nation’s fourth-largest city, in a subtropical region with high travel volume to Latin America and the Caribbean, Houston was an ideal location for studying experiences encountered by clinicians and public health officials as they responded to the Zika virus crisis. To identify the challenges encountered in the response and to explore strategies to improve future responses to emerging infectious diseases, we interviewed 38 key stakeholders who were clinical, scientific, operational, and public health leaders. From the responses, we identified 4 key challenges: testing, travel screening, patient demographics and immigration status, and insufficient collaboration . We also identified 5 strategic areas as potential solutions: improved electronic health record support, specialty centers and referral systems, standardized forms, centralized testing databases, and joint academic/public health task forces. Since 2015, this virus has infected >1 million persons in 70 countries  mobilized rapidly. Nevertheless, considerable work was needed by those on the ground to translate CDC guidelines and other emerging research into actionable policies at the institutional level.Aedes aegypti and Ae. albopictus mosquitoes  and used qualitative coding to identify key themes related to challenges and strategies in the Zika virus response.We conducted semistructured interviews of 38 clinical, scientific, and public health experts in Houston and current or former Texas public health officials . Almost From stakeholders’ discussions of the challenges encountered in responding to Zika virus infection, 4 primary themes emerged. These themes were testing, travel screening, patient demographics and immigration status, and collaboration  .The most commonly described challenges were associated with Zika virus testing. Every clinician interviewed described such challenges. Five testing issues emerged.First, clinicians described logistics burdens associated with collecting and submitting samples to public health departments, characterizing the paperwork and approval processes as “redundant,” “very time-consuming,” and “a significant barrier to care.” One case described by an obstetrician exemplifies these challenges. To order serologic testing, the obstetrician had to complete hospital send-out laboratory forms and 3 forms from the Houston Health Department (HHD) and telephone HHD for approval. When the test results returned positive, the clinical team sent a plaque-reduction neutralization test (PRNT) sample to CDC to rule out cross-reactivity with other flaviviruses  integration for ordering and reporting test results. Clinicians reported resorting to “clunky” workarounds, such as receiving a facsimile from the health department that then had to be scanned into the medical record. Providers expressed concern that such systems could lead to insufficient follow-up, particularly for care of neonates. For example, a pediatrician cited the challenges of exchanging and recording testing data as the reason why one infant in her practice was not evaluated for congenital Zika syndrome until 4 months of age—months beyond the CDC recommendations for evaluation and management of possible congenital infection   should primarily be responsible for long-term evaluation of Zika virus–exposed infants.Respondents identified numerous ways in which technology could streamline testing processes, starting from the initial stage of screening patients, progressing to collecting and submitting samples, and then documenting and sharing results among providers and public health systems. Five specific respondent suggestions for improved EHR support were 1) standardizing screening questions within the patient’s EHR to ensure accurate assessment of risk exposure; 2) implementing EHR-based decision support systems to help providers select and order the appropriate test(s); 3) enabling electronic ordering of Zika virus testing through the EHR; 4) prepopulating demographic information within the test form to reduce provider time burden and improve the efficiency of public health case investigations; and 5) integrating the testing laboratory and patient EHR to enable test results to be automatically entered into the patient EHR.,Admittedly, revising an EHR system can be an unwieldy process , involving key stakeholders, and using electronic tools for low-cost dissemination , leadership should designate an emerging infectious disease point person or committee with the authority and support to rapidly create an ad hoc task force comprising interdisciplinary members needed to effectively address a public health emergency. Diverse representation will be vital to the success of such committees, including clinical leadership to translate national, state, or local algorithms to clinical management plans for the respective institutional contexts; health information management leaders to modify and implement EHR changes to support the clinical response; laboratory personnel to guide testing processes; and communications experts to disseminate guidance on policy and process throughout the institution.For this project, we purposefully selected clinical, operational, and public health leaders with experience responding to Zika virus infections. Consequently, obstetricians, pediatricians, and infectious disease specialists working in academic medical centers were overrepresented. Their experiences shed insight into features of health system capacity and preparedness to respond to an emerging infectious disease. However, involvement of other stakeholders, particularly patients and primary care providers in nonacademic, rural, and resource-poor settings, probably would have provided additional insights..The suggestions for improvement reflect issues raised by our respondents and are not exhaustive. Other critical issues merit further attention, including how healthcare providers can ensure that patients feel safe to access needed health services in the face of contemporary government approaches to immigration enforcement (The emergence of Zika virus brought numerous challenges to the health system in Houston. Although the virus itself was relatively new, many of the issues confronted by providers and public health officials in the face of the disease were far from novel. Instead, the issues were often the result of known, predictable, and recurring shortcomings in our healthcare system. The insights of expert stakeholders led us to suggest several strategies for improving the response to Zika virus and other future emerging infectious diseases.