Health research policy: a case study of policy change in Aboriginal and Torres Strait Islander health research

The need for research to better address health disparities in Indigenous people has been widely recognised. This paper examines past policies and outlines issues for Indigenous health policy in the future. There is considerate potential for health research to contribute to better health services and programs and improved health outcomes; the policies of health research funding agencies are critical to achieving health gains from research. This paper (i) describes the policy changes by NHMRC from 1997 to 2002 to improve funding of Aboriginal health research (ii) examines the catalysts for the policy changes (iii) describes the extent to which this has resulted in new models of research and (iv) outlines issues for Indigenous health policy in the future. &nbsp

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Prevention and early detection of prostate cancer

This Review was sponsored and funded by the International Society of Cancer Prevention (ISCaP), the European Association of Urology (EAU), the National Cancer Institute, USA (NCI) (grant number 1R13CA171707-01), Prostate Cancer UK, Cancer Research UK (CRUK) (grant number C569/A16477), and the Association for International Cancer Research (AICR

Developmental programming: State-of-the-science and future directions-Summary from a Pennington Biomedical symposium.

OBJECTIVE: On December 8-9, 2014, the Pennington Biomedical Research Center convened a scientific symposium to review the state-of-the-science and future directions for the study of developmental programming of obesity and chronic disease. The objectives of the symposium were to discuss: (i) past and current scientific advances in animal models, population-based cohort studies, and human clinical trials, (ii) the state-of-the-science of epigenetic-based research, and (iii) considerations for future studies. RESULTS: This symposium provided a comprehensive assessment of the state of the scientific field and identified research gaps and opportunities for future research in order to understand the mechanisms contributing to the developmental programming of health and disease. CONCLUSIONS: Identifying the mechanisms which cause or contribute to developmental programming of future generations will be invaluable to the scientific and medical community. The ability to intervene during critical periods of prenatal and early postnatal life to promote lifelong health is the ultimate goal. Considerations for future research including the use of animal models, the study design in human cohorts with considerations about the timing of the intrauterine exposure, and the resulting tissue-specific epigenetic signature were extensively discussed and are presented in this meeting summary.The symposium was funded by NORC Center Grant P30DK072476 from the NIDDK. LAG is supported by T32DK064584 from the NIDDK. Work in MS Laboratory was supported by MOP‐42411 from the Canadian Institute of Health Research. Work in JAM Laboratory was supported by the Center for Nutrition Research at the University of Navarra in Pamplona, Spain. RAW is supported by a grant from the U.S. Department of Agriculture (USDA) [CRIS 3092‐5‐001‐059]. Work in BTH Laboratory was supported by the National Institutes of Health (R01AG042190) and the European Union's Seventh Framework Program IDEAL (FP7/2007‐2011; grant agreement No. 259679). Work in CL Laboratory was funded by The Swedish Research Council and The Novo Nordisk Foundation. SEO is a member of the University of Cambridge MRC Metabolic Diseases Unit. MFH is the recipient of an American Diabetes Association (ADA) Pathways To Stop Diabetes Award. Work in ER and LMR Laboratories was partially funded by a NORC grant titled “Nutritional Programming: Environmental and Molecular Interactions” to ER (P30DK072476)

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

The Colletotrichum acutatum species complex as a model system to study evolution and host specialization in plant pathogens

PerspectiveColletotrichum spp. infect a wide diversity of hosts, causing plant diseases on many economically important crops worldwide. The genus contains approximately 189 species organized into at least 11 major phylogenetic lineages, also known as species complexes. The Colletotrichum acutatum species complex is a diverse yet relatively closely related group of plant pathogenic fungi within this genus. Within the species complex we find a wide diversity of important traits such as host range and host preference, mode of reproduction and differences in the strategy used to infect their hosts. Research on fungal comparative genomics have attempted to find correlations in these traits and patterns of gene family evolution but such studies typically compare fungi from different genera or even different fungal Orders. The C. acutatum species complex contains most of this diversity within a group of relatively closely related species. This Perspective article presents a review of the current knowledge on C. acutatum phylogeny, biology, and pathology. It also demonstrates the suitability of C. acutatum for the study of gene family evolution on a fine scale to uncover evolutionary events in the genome that are associated with the evolution of phenotypic characters important for host interactions.info:eu-repo/semantics/publishedVersio

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development

Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice

<div><p>Objective</p><p>Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.</p><p>Methods</p><p>Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.</p><p>Results</p><p>Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10^-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10^-2). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).</p><p>Conclusions</p><p>A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the <i>in vivo</i> pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</p></div

Induction of labour versus expectant monitoring in women with pregnancy induced hypertension or mild preeclampsia at term: the HYPITAT trial

Contains fulltext : 53183.pdf ( ) (Open Access)BACKGROUND: Hypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to 15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates. METHODS/DESIGN: Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%. DISCUSSION: This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications. TRIAL REGISTRATION: The protocol is registered in the clinical trial register number ISRCTN08132825