313 research outputs found

    Background risk of breast cancer and the association between physical activity and mammographic density

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    This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0

    Teeth

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    Lessons Learned from Initial Piloting of Farmer-Orientated Value Chain Training in the Pacific

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    There have been numerous initiatives in the Pacific region over the past decade to mainstream the concept of value chains into the agricultural development arena. Since 2012, the ACP/EU Technical Centre for Agricultural and Rural Cooperation (CTA) has been at the forefront of value chain development in the Pacific region, supporting a number of value chain studies and the publication of the ‘Agricultural Value Chain Guide for the Pacific Islands’. This CTA guide was intended to provide a simplified approach to value chain analysis and therefore make that approach useful to ‘farmers, traders and policy makers’. From 2014-2017, the Pacific Island Farmers Organisation Network (PIFON) implemented a programme to pilot farmer-orientated value chain training through its farmer organisation members. The CTA guide was used and the training sessions were supported through several externally funded projects, including the IFAD/SDC1 funded MTCP II project and the EU/SPC PAPP project. PIFON believes that farmer organisations have an important role to play in disseminating key information to their members and in helping to ‘extend the reach of government and aid agencies’. These VC training sessions targeted chain actors involved in the: 1. Value chain for spices in Vanuatu (through the Farm Support Association and Venui Vanilla) 2. Value chain for ginger in Fiji (through Fiji Crop and Livestock Council) 3. Value chain for papaya in Tonga (through Growers Federation of Tonga) 4. Value chain for Taro in Fiji (through Tei Tei Taveuni and the Tutu Rural Training Centre) 5. Value chain for papaya in Fiji (through Nature’s Way Cooperative) CTA is currently implementing a project entitled ‘Promoting Nutritious Food Systems in the Pacific Islands’ (2016-2020), in partnership with the International Fund for Agricultural Development (IFAD) and the Pacific Islands Private Sector Organisation (PIPSO). Under this project, CTA has commissioned PIFON to document the lessons learned about the value chain training, through production of a video and this publication. This report explores a range of impacts of the initial piloting of value chain training in the Pacific. These included: • The beginnings of a change in the mind-set of the actors in the value chain –particularly farmers • The incorporation of the value chain ‘way of thinking’ into normal extension activities of farmer organisations • Improvements in relationships and better collaboration • Increased supply of produce • Value chain training materials being translated/adapted/adopted into training programme

    Physical rehabilitation interventions for adult patients with critical illness across the continuum of recovery: an overview of systematic reviews protocol

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    Background: Patients admitted to the intensive care unit with critical illness often experience significant physical\ud impairments, which typically persist for many years following resolution of the original illness. Physical rehabilitation\ud interventions that enhance restoration of physical function have been evaluated across the continuum of recovery\ud following critical illness including within the intensive care unit, following discharge to the ward and beyond hospital\ud discharge. Multiple systematic reviews have been published appraising the expanding evidence investigating these\ud physical rehabilitation interventions, although there appears to be variability in review methodology and quality. We\ud aim to conduct an overview of existing systematic reviews of physical rehabilitation interventions for adult intensive\ud care patients across the continuum of recovery.\ud Methods/design: This protocol has been developed according to the Preferred Reporting Items for Systematic\ud Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. We will search the Cochrane Systematic Review Database,\ud Database of Abstracts of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials, MEDLINE, Excerpta\ud Medica Database and Cumulative Index to Nursing and Allied Health Literature databases. We will include systematic\ud reviews of randomised controlled trials of adult patients, admitted to the intensive care unit and who have received\ud physical rehabilitation interventions at any time point during their recovery. Data extraction will include systematic\ud review aims and rationale, study types, populations, interventions, comparators, outcomes and quality appraisal\ud method. Primary outcomes of interest will focus on findings reflecting recovery of physical function. Quality of\ud reporting and methodological quality will be appraised using the PRISMA checklist and the Assessment of Multiple\ud Systematic Reviews tool.\ud Discussion: We anticipate the findings from this novel overview of systematic reviews will contribute to the synthesis\ud and interpretation of existing evidence regarding physical rehabilitation interventions and physical recovery in post-critical\ud illness patients across the continuum of recovery

    Competing risks of death in women treated with adjuvant aromatase inhibitors for early breast cancer on NCIC CTG MA.27

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    Baseline patient and tumor characteristics differentially affected type of death in the MA.17 placebo-controlled letrozole trial where cardiovascular death was not separately identified. The MA.27 trial allowed competing risks analysis of breast cancer (BC), cardiovascular, and other type (OT) of death. MA.27 was a phase III adjuvant breast cancer trial of exemestane versus anastrozole. Effects of baseline patient and tumor characteristics were tested for whether factors were associated with (1) all cause mortality and (2) cause-specific mortality. We also fit step-wise forward cause-specific-adjusted models. 7576 women (median age 64 years; 5417 (72 %) < 70 years and 2159 (28 %) ≥ 70 years) were enrolled and followed for median 4.1 years. The 432 deaths comprised 187 (43 %) BC, 66 (15 %) cardiovascular, and 179 (41 %) OT. Five baseline factors were differentially associated with type of death. Older patients had greater BC (p = 0.03), cardiovascular (p < 0.001), and other types (p < 0.001) of mortality. Patients with pre-existing cardiovascular history had worse cardiovascular mortality (p < 0.001); those with worse ECOG performance status had worse OT mortality (p < 0.001). Patients with T1 tumors (p < 0.001) and progesterone receptor positive had less BC mortality (p < 0.001). Fewer BC deaths occurred with node-negative disease (p < 0.001), estrogen receptor-positive tumors (p = 0.001), and without adjuvant chemotherapy (p = 0.005); worse cardiovascular mortality (p = 0.01), with trastuzumab; worse OT mortality, for non-whites (p = 0.03) and without adjuvant radiotherapy (p = 0.003). Overall, 57 % of deaths in MA.27 AI-treated patients were non-breast cancer related. Baseline patient and tumor characteristics differentially affected type of death with women 70 or older experiencing more non-breast cancer death

    Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

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    Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

    Discovery of an Allosteric Binding Site in Kinetoplastid Methionyl-tRNA Synthetase

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    Methionyl-tRNA synthetase (MetRS) is a chemically validated drug target in kinetoplastid parasites Trypanosoma brucei and Leishmania donovani. To date, all kinetoplastid MetRS inhibitors described bind in a similar way to an expanded methionine pocket and an adjacent, auxiliary pocket. In the current study, we have identified a structurally novel class of inhibitors containing a 4,6-diamino-substituted pyrazolopyrimidine core (the MetRS02 series). Crystallographic studies revealed that MetRS02 compounds bind to an allosteric pocket in L. major MetRS not previously described, and enzymatic studies demonstrated a noncompetitive mode of inhibition. Homology modeling of the Trypanosoma cruzi MetRS enzyme revealed key differences in the allosteric pocket between the T. cruzi and Leishmania enzymes. These provide a likely explanation for the lower MetRS02 potencies that we observed for the T. cruzi enzyme compared to the Leishmania enzyme. The identification of a new series of MetRS inhibitors and the discovery of a new binding site in kinetoplastid MetRS enzymes provide a novel strategy in the search for new therapeutics for kinetoplastid diseases.</p
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