35 research outputs found

    Aboriginal Maple Syrup Values Summary

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    This report examines the values associated with maple syrup practices in Aboriginal contexts. It is based on fifteen interviews conducted with Aboriginal people who have knowledge of maple syrup practices in Ontario. The interviewees included both First Nations and Metis people

    Encouragement and distortionary effects of conditional cash transfers

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    Conditional cash transfer (CCT) programs have become increasingly popular as a development strategy. These programs aim to reduce poverty or achieve other social goals by making the transfers conditional upon the receivers\u27 actions. Conditions are designed to encourage some desirable behavior that recipients might otherwise under-invest in. An unintended consequence of the conditionality may be to distort recipients\u27 actions in ways that lower their welfare. The transfer size plays an important role in shaping such distortionary effects. In certain circumstances, a larger transfer increases distortion more than that it raises benefits from stronger encouragement, implying that (i) there is an optimal transfer size for CCTs, and (ii) unconditional cash transfers (UCTs) may be better than CCTs when the transfer amount is large. We illustrate a range of distortions arising from CCT programs around the world. We then introduce an experimental design that permits a test of this distortionary effect, and implement it in a cash transfer program conditional on seasonal labor migration in rural Indonesia. We find that when the transfer size exceeds the amount required for travel expenses, the distortion created induces additional individuals to migrate who have lower (possibly even negative) migration returns, weakening overall program impacts

    Similar Gene Estimates from Circular and Linear Standards in Quantitative PCR Analyses Using the Prokaryotic 16S rRNA Gene as a Model

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    Conceived and designed the experiments: ALO KED. Performed the experiments: ALO. Analyzed the data: ALO. Contributed reagents/materials/analysis tools: KED. Wrote the paper: ALO KED. Revised and approved final version of paper: ALO KED.Quantitative PCR (qPCR) is one of the most widely used tools for quantifying absolute numbers of microbial gene copies in test samples. A recent publication showed that circular plasmid DNA standards grossly overestimated numbers of a target gene by as much as 8-fold in a eukaryotic system using quantitative PCR (qPCR) analysis. Overestimation of microbial numbers is a serious concern in industrial settings where qPCR estimates form the basis for quality control or mitigation decisions. Unlike eukaryotes, bacteria and archaea most commonly have circular genomes and plasmids and therefore may not be subject to the same levels of overestimation. Therefore, the feasibility of using circular DNA plasmids as standards for 16S rRNA gene estimates was assayed using these two prokaryotic systems, with the practical advantage being rapid standard preparation for ongoing qPCR analyses. Full-length 16S rRNA gene sequences from Thermovirga lienii and Archaeoglobus fulgidus were cloned and used to generate standards for bacterial and archaeal qPCR reactions, respectively. Estimates of 16S rRNA gene copies were made based on circular and linearized DNA conformations using two genomes from each domain: Desulfovibrio vulgaris, Pseudomonas aeruginosa, Archaeoglobus fulgidus, and Methanocaldocococcus jannaschii. The ratio of estimated to predicted 16S rRNA gene copies ranged from 0.5 to 2.2-fold in bacterial systems and 0.5 to 1.0-fold in archaeal systems, demonstrating that circular plasmid standards did not lead to the gross over-estimates previously reported for eukaryotic systems.Yeshttp://www.plosone.org/static/editorial#pee

    Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

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    Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice

    Call for emergency action to restore dietary diversity and protect global food systems in times of COVID-19 and beyond: Results from a cross-sectional study in 38 countries

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    Background: The COVID-19 pandemic has revealed the fragility of the global food system, sending shockwaves across countries\u27 societies and economy. This has presented formidable challenges to sustaining a healthy and resilient lifestyle. The objective of this study is to examine the food consumption patterns and assess diet diversity indicators, primarily focusing on the food consumption score (FCS), among households in 38 countries both before and during the first wave of the COVID-19 pandemic. Methods: A cross-sectional study with 37 207 participants (mean age: 36.70 ± 14.79, with 77 % women) was conducted in 38 countries through an online survey administered between April and June 2020. The study utilized a pre-tested food frequency questionnaire to explore food consumption patterns both before and during the COVID-19 periods. Additionally, the study computed Food Consumption Score (FCS) as a proxy indicator for assessing the dietary diversity of households. Findings: This quantification of global, regional and national dietary diversity across 38 countries showed an increment in the consumption of all food groups but a drop in the intake of vegetables and in the dietary diversity. The household\u27s food consumption scores indicating dietary diversity varied across regions. It decreased in the Middle East and North Africa (MENA) countries, including Lebanon (p \u3c 0.001) and increased in the Gulf Cooperation Council countries including Bahrain (p = 0.003), Egypt (p \u3c 0.001) and United Arab Emirates (p = 0.013). A decline in the household\u27s dietary diversity was observed in Australia (p \u3c 0.001), in South Africa including Uganda (p \u3c 0.001), in Europe including Belgium (p \u3c 0.001), Denmark (p = 0.002), Finland (p \u3c 0.001) and Netherland (p = 0.027) and in South America including Ecuador (p \u3c 0.001), Brazil (p \u3c 0.001), Mexico (p \u3c 0.0001) and Peru (p \u3c 0.001). Middle and older ages [OR = 1.2; 95 % CI = [1.125–1.426] [OR = 2.5; 95 % CI = [1.951–3.064], being a woman [OR = 1.2; 95 % CI = [1.117–1.367], having a high education (p \u3c 0.001), and showing amelioration in food-related behaviors [OR = 1.4; 95 % CI = [1.292–1.709] were all linked to having a higher dietary diversity. Conclusion: The minor to moderate changes in food consumption patterns observed across the 38 countries within relatively short time frames could become lasting, leading to a significant and prolonged reduction in dietary diversity, as demonstrated by our findings

    External validation of prognostic models predicting pre-eclampsia : individual participant data meta-analysis

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    Abstract Background Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. Methods IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. Results Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model’s calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. Conclusions The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. Trial registration PROSPERO ID: CRD42015029349

    The Impact of Musculoskeletal Injuries Sustained in Road Traffic Crashes on Work-Related Outcomes: A Systematic Review

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    Musculoskeletal injuries occur frequently after road traffic crashes (RTCs), and the effect on work participation is not fully understood. The primary aim of this review was to determine the impact of sustaining a musculoskeletal injury during an RTC on the rate of return to work (RTW), sick leave, and other work outcomes. The secondary aim was to determine factors associated with these work-related outcomes. An electronic search of relevant databases to identify observational studies related to work and employment, RTC, and musculoskeletal injuries was conducted. Where possible, outcome data were pooled by follow-up period to answer the primary aim. Fifty-three studies were included in this review, of which 28 were included in meta-analyses. The pooled rate of RTW was 70% at 1 month, 67% at 3 months, 76% at 6 months, 83% at 12 months, and 70% at 24 months. Twenty-seven percent of participants took some sick leave by one month follow-up, 13% by 3 months, 23% by 6 months, 36% by 12 months, and 22% by 24 months. Most of the factors identified as associated with work outcomes were health-related, with some evidence also for sociodemographic factors. While 70% of people with RTC-related musculoskeletal injury RTW shortly after accident, many still have not RTW two years later

    Effect of exercise on pain processing and motor output in people with knee osteoarthritis: a systematic review and meta-analysis

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    Objective: Guidelines recommend exercise as a core treatment for knee osteoarthritis. However, it is unclear how exercise affects measures of pain processing and motor function. The aim was to evaluate the effect of exercise on measures of pain processing and motor function in people with knee osteoarthritis. Methods: We searched five electronic databases (MEDLINE, EMBASE, CINAHL, SCOPUS and Cochrane Central Register of Controlled Trials) for studies on knee osteoarthritis, of any design, evaluating pain processing and motor function before and after exercise. Data were pooled with random-effects meta-analysis. Study quality was assessed using the Downs and Black and quality of evidence was assessed using the GRADE. Results: Eighteen studies were eligible and 16 were included. Following acute exercise, pressure pain threshold increased local to the study limb (standardised mean difference [95% CI] 0.26, [0.02, 0.51], n=159 from 5 studies), but there was no statistically significant change remote from the study limb (0.09, [-0.11, 0.29], n=90 from 4 studies). Following an exercise program (range 5-12 weeks) there were no statistically significant changes in pressure pain threshold (local 0.23, [-0.01, 0.47], n=218 from 8 studies; remote 0.33 [-0.13, 0.79], n=76 from 4 studies), temporal pain summation (0.38 [-0.08, 0.85], n=122 from 3 studies) or voluntary quadriceps muscle activation (4.23% [-1.84 to 10.30], n=139 from 4 studies). Conclusion: Very-low quality evidence suggests that pressure pain threshold increases following acute exercise. Very-low quality evidence suggests that pressure pain threshold, temporal pain summation or voluntary quadriceps activation do not change statistically significantly following exercise programs
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