98 research outputs found
Investigating Financial Incentives for Maternal Health: An Introduction
Projection of current trends in maternal and neonatal mortality
reduction shows that many countries will fall short of the UN
Millennium Development Goal 4 and 5. Underutilization of maternal
health services contributes to this poor progress toward reducing
maternal and neonatal morbidity and mortality. Moreover, the quality of
services continues to lag in many countries, with a negative effect on
the health of women and their babies, including deterring women from
seeking care. To enhance the use and provision of quality maternal
care, countries and donors are increasingly using financial incentives.
This paper introduces the JHPN Supplement, in which each paper reviews
the evidence of the effectiveness of a specific financial incentive
instrument with the aim of improving the use and quality of maternal
healthcare and impact. The US Agency for International Development and
the US National Institutes of Health convened a US Government Evidence
Summit on Enhancing Provision and Use of Maternal Health Services
through Financial Incentives on 24-25 April 2012 in Washington, DC. The
Summit brought together leading global experts in finance, maternal
health, and health systems from governments, academia, development
organizations, and foundations to assess the evidence on whether
financial incentives significantly and substantially increase
provision, use and quality of maternal health services, and the
contextual factors that impact the effectiveness of these incentives.
Evidence review teams evaluated the multidisciplinary evidence of
various financial mechanisms, including supply-side incentives (e.g.
performance-based financing, user fees, and various insurance
mechanisms) and demand-side incentives (e.g. conditional cash
transfers, vouchers, user fee exemptions, and subsidies for
care-seeking). At the Summit, the teams presented a synthesis of
evidence and initial recommendations on practice, policy, and research
for discussion. The Summit enabled structured feedback on
recommendations which the teams included in their final papers
appearing in this Supplement. Papers in this Supplement review the
evidence for a specific financial incentive mechanism (e.g. pay for
performance, conditional cash transfer) to improve the use and quality
of maternal healthcare and makes recommendations for programmes and
future research. While data on programmes using financial incentives
for improved use and indications of the quality of maternal health
services support specific conclusions and recommendations, including
those for future research, data linking the use of financial incentives
with improved health outcomes are minimal
High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control
To improve the power of mediation in high-throughput studies, here we introduce High-throughput mediation analysis (Hitman), which accounts for direction of mediation and applies empirical Bayesian linear modeling. We apply Hitman in a retrospective, exploratory analysis of the SLIMM-T2D clinical trial in which participants with type 2 diabetes were randomized to Roux-en-Y gastric bypass (RYGB) or nonsurgical diabetes/weight management, and fasting plasma proteome and metabolome were assayed up to 3 years. RYGB caused greater improvement in HbA1c, which was mediated by growth hormone receptor (GHR). GHR’s mediation is more significant than clinical mediators, including BMI. GHR decreases at 3 months postoperatively alongside increased insulin-like growth factor binding proteins IGFBP1/BP2; plasma GH increased at 1 year. Experimental validation indicates (1) hepatic GHR expression decreases in post-bariatric rats; (2) GHR knockdown in primary hepatocytes decreases gluconeogenic gene expression and glucose production. Thus, RYGB may induce resistance to diabetogenic effects of GH signaling
Financial Incentives and Maternal Health: Where Do We Go from Here?
Health financing strategies that incorporate financial incentives are
being applied in many low- and middle-income countries, and improving
maternal and neonatal health is often a central goal. As yet, there
have been few reviews of such programmes and their impact on maternal
health. The US Government Evidence Summit on Enhancing Provision and
use of Maternal Health Services through Financial Incentives was
convened on 24-25 April 2012 to address this gap. This article, the
final in a series assessing the effects of financial
incentives\u2014performance-based incentives (PBIs), insurance, user
fee exemption programmes, conditional cash transfers, and
vouchers\u2014summarizes the evidence and discusses issues of context,
programme design and implementation, cost-effectiveness, and
sustainability. We suggest key areas to consider when designing and
implementing financial incentive programmes for enhancing maternal
health and highlight gaps in evidence that could benefit from
additional research. Although the methodological rigor of studies
varies, the evidence, overall, suggests that financial incentives can
enhance demand for and improve the supply of maternal health services.
Definitive evidence demonstrating a link between incentives and
improved health outcomes is lacking; however, the evidence suggests
that financial incentives can increase the quantity and quality of
maternal health services and address health systems and financial
barriers that prevent women from accessing and providers from
delivering quality, lifesaving maternal healthcare
The anti-SARS-CoV-2 monoclonal antibody, bamlanivimab, minimally impacts the endogenous immune response to COVID-19 vaccination
As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccine rollout progresses, the availability and demand for monoclonal antibodies for the prevention and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also accelerating. This longitudinal serological study evaluated the magnitude and potency of the endogenous antibody response to COVID-19 vaccination in participants who first received a COVID-19 monoclonal antibody in a prevention study. Over the course of six months, serum samples were collected from a population of nursing home residents and staff enrolled in a clinical trial who were randomized to either bamlanivimab treatment or placebo. In an unplanned component of this trial, a subset of these participants was subsequently fully vaccinated with two doses of either SpikeVax (Moderna) or Comirnaty (BioNTech/Pfizer) COVID-19 mRNA vaccines. This post-hoc analysis assessed the immune response to vaccination for 135 participants without prior SARS-CoV-2 infection. Antibody titers and potency were assessed using three assays against SARS-CoV-2 proteins that bamlanivimab does not efficiently bind to, thereby reflecting the endogenous antibody response. All bamlanivimab and placebo recipients mounted a robust immune response to full COVID-19 vaccination, irrespective of age, risk-category, and vaccine type with any observed differences of uncertain clinical importance. These findings are pertinent for informing public health policy with results that suggest that the benefit of receiving COVID-19 vaccination at the earliest opportunity outweighs the minimal effect on the endogenous immune response due to prior prophylactic COVID-19 monoclonal antibody infusion
Sterol Intermediates of Cholesterol Biosynthesis Inhibit Hair Growth and Trigger an Innate Immune Response in Cicatricial Alopecia
Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders
A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias
Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically-reliable diagnostic test and minimize false-negative results we developed an open-source tool (CoverMi) to accurately determine base-coverage and the ‘discoverability’ of known mutations for every sample. We validated our 33-gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS-based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family
The emergence of modern statistics in agricultural science : Analysis of variance, experimental design and the reshaping of research at Rothamsted Experimental Station, 1919–1933
During the twentieth century statistical methods have transformed research in the experimental and social sciences. Qualitative evidence has largely been replaced by quantitative results and the tools of statistical inference have helped foster a new ideal of objectivity in scientific knowledge. The paper will investigate this transformation by considering the genesis of analysis of variance and experimental design, statistical methods nowadays taught in every elementary course of statistics for the experimental and social sciences. These methods were developed by the mathematician and geneticist R. A. Fisher during the 1920s, while he was working at Rothamsted Experimental Station, where agricultural research was in turn reshaped by Fisher’s methods. Analysis of variance and experimental design required new practices and instruments in field and laboratory research, and imposed a redistribution of expertise among statisticians, experimental scientists and the farm staff. On the other hand the use of statistical methods in agricultural science called for a systematization of information management and made computing an activity integral to the experimental research done at Rothamsted, permanently integrating the statisticians’ tools and expertise into the station research programme. Fisher’s statistical methods did not remain confined within agricultural research and by the end of the 1950s they had come to stay in psychology, sociology, education, chemistry, medicine, engineering, economics, quality control, just to mention a few of the disciplines which adopted them
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