Daily to decadal modulation of jet variability

The variance of a jet’s position in latitude is found to be related to its average speed: when a jet becomes stronger its variability in latitude decreases. This relationship is shown to hold for observed midlatitude jets around the world and also across a hierarchy of numerical models. North Atlantic jet variability is shown to be modulated on decadal timescales, with decades of a strong, steady jet being interspersed with decades of a weak, variable jet. These modulations are also related to variations in the basin-wide occurrence of high-impact blocking events. A picture emerges of complex multidecadal jet variability in which recent decades do not appear unusual. We propose an underlying barotropic mechanism to explain this behaviour, related to the change in refractive properties of a jet as it strengthens, and the subsequent effect on the distribution of Rossby wave breaking

Observation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies.

Misfolded α-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson's disease (PD). A large body of evidence shows that α-synuclein can aggregate into amyloid fibrils, but the relationship between α-synuclein self-assembly and Lewy body formation remains unclear. Here, we show, both in vitro and in a Caenorhabditis elegans model of PD, that α-synuclein undergoes liquid‒liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel with Lewy-body-like properties. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro. Taken together, these results suggest that the formation of Lewy bodies may be linked to the arrested maturation of α-synuclein condensates in the presence of lipids and other cellular components.Wellcome Trust (065807/Z/01/Z) (203249/Z/16/Z). Also, the UK Medical Research Council (MRC) (MR/K02292X/1), Alzheimer Research UK (ARUK) (ARUK-PG013-14), Michael J Fox Foundation (16238) and from Infinitus China Ltd

Stress urinary incontinence surgery trends in academic female pelvic medicine and reconstructive surgery urology practice in the setting of the food and drug administration public health notifications

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136665/1/nau23080.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136665/2/nau23080_am.pd

A Mathematical Approach Lights up The Way to End Cholera Transmission

Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies.We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1-14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies.We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions

A Randomized Phase 4 Study of Immunogenicity and Safety After Monovalent Oral Type 2 Sabin Poliovirus Vaccine Challenge in Children Vaccinated with Inactivated Poliovirus Vaccine in Lithuania.

BACKGROUND: Understanding immunogenicity and safety of monovalent type 2 oral poliovirus vaccine (mOPV2) in inactivated poliovirus vaccine (IPV)-immunized children is of major importance in informing global policy to control circulating vaccine-derived poliovirus outbreaks. METHODS: In this open-label, phase 4 study (NCT02582255) in 100 IPV-vaccinated Lithuanian 1-5-year-olds, we measured humoral and intestinal type 2 polio neutralizing antibodies before and 28 days after 1 or 2 mOPV2 doses given 28 days apart and measured stool viral shedding after each dose. Parents recorded solicited adverse events (AEs) for 7 days after each dose and unsolicited AEs for 6 weeks after vaccination. RESULTS: After 1 mOPV2 challenge, the type 2 seroprotection rate increased from 98% to 100%. Approximately 28 days after mOPV2 challenge 34 of 68 children (50%; 95% confidence interval, 38%-62%) were shedding virus; 9 of 37 (24%; 12%-41%) were shedding 28 days after a second challenge. Before challenge, type 2 intestinal immunity was undetectable in IPV-primed children, but 28 of 87 (32%) had intestinal neutralizing titers ≥32 after 1 mOPV2 dose. No vaccine-related serious or severe AEs were reported. CONCLUSIONS: High viral excretion after mOPV2 among exclusively IPV-vaccinated children was substantially lower after a subsequent dose, indicating induction of intestinal immunity against type 2 poliovirus

How should HIV resources be allocated? Lessons learnt from applying Optima HIV in 23 countries.

INTRODUCTION: With limited funds available, meeting global health targets requires countries to both mobilize and prioritize their health spending. Within this context, countries have recognized the importance of allocating funds for HIV as efficiently as possible to maximize impact. Over the past six years, the governments of 23 countries in Africa, Asia, Eastern Europe and Latin America have used the Optima HIV tool to estimate the optimal allocation of HIV resources. METHODS: Each study commenced with a request by the national government for technical assistance in conducting an HIV allocative efficiency study using Optima HIV. Each study team validated the required data, calibrated the Optima HIV epidemic model to produce HIV epidemic projections, agreed on cost functions for interventions, and used the model to calculate the optimal allocation of available funds to best address national strategic plan targets. From a review and analysis of these 23 country studies, we extract common themes around the optimal allocation of HIV funding in different epidemiological contexts. RESULTS AND DISCUSSION: The optimal distribution of HIV resources depends on the amount of funding available and the characteristics of each country's epidemic, response and targets. Universally, the modelling results indicated that scaling up treatment coverage is an efficient use of resources. There is scope for efficiency gains by targeting the HIV response towards the populations and geographical regions where HIV incidence is highest. Across a range of countries, the model results indicate that a more efficient allocation of HIV resources could reduce cumulative new HIV infections by an average of 18% over the years to 2020 and 25% over the years to 2030, along with an approximately 25% reduction in deaths for both timelines. However, in most countries this would still not be sufficient to meet the targets of the national strategic plan, with modelling results indicating that budget increases of up to 185% would be required. CONCLUSIONS: Greater epidemiological impact would be possible through better targeting of existing resources, but additional resources would still be required to meet targets. Allocative efficiency models have proven valuable in improving the HIV planning and budgeting process

Meeting human resources for health staffing goals by 2018: a quantitative analysis of policy options in Zambia

<p>Abstract</p> <p>Background</p> <p>The Ministry of Health (MOH) in Zambia is currently operating with fewer than half of the health workers required to deliver basic health services. The MOH has developed a human resources for health (HRH) strategic plan to address the crisis through improved training, hiring, and retention. However, the projected success of each strategy or combination of strategies is unclear.</p> <p>Methods</p> <p>We developed a model to forecast the size of the public sector health workforce in Zambia over the next ten years to identify a combination of interventions that would expand the workforce to meet staffing targets. The key forecasting variables are training enrolment, graduation rates, public sector entry rates for graduates, and attrition of workforce staff. We model, using Excel (Office, Microsoft; 2007), the effects of changes in these variables on the projected number of doctors, clinical officers, nurses and midwives in the public sector workforce in 2018.</p> <p>Results</p> <p>With no changes to current training, hiring, and attrition conditions, the total number of doctors, clinical officers, nurses, and midwives will increase from 44% to 59% of the minimum necessary staff by 2018. No combination of changes in staff retention, graduation rates, and public sector entry rates of graduates by 2010, without including training expansion, is sufficient to meet staffing targets by 2018 for any cadre except midwives. Training enrolment needs to increase by a factor of between three and thirteen for doctors, three and four for clinical officers, two and three for nurses, and one and two for midwives by 2010 to reach staffing targets by 2018. Necessary enrolment increases can be held to a minimum if the rates of retention, graduation, and public sector entry increase to 100% by 2010, but will need to increase if these rates remain at 2008 levels.</p> <p>Conclusions</p> <p>Meeting the minimum need for health workers in Zambia this decade will require an increase in health training school enrolment. Supplemental interventions targeting attrition, graduation and public sector entry rates can help close the gap. HRH modelling can help MOH policy makers determine the relative priority and level of investment needed to expand Zambia's workforce to target staffing levels.</p

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans : joint RENEB and EURADOS inter-laboratory comparisons

Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios

Directed Evaluation of Enterotoxigenic Escherichia coli Autotransporter Proteins as Putative Vaccine Candidates

Diarrheal diseases are responsible for more than 1.5 million deaths annually in developing countries. Enterotoxigenic E. coli (ETEC) are among the most common bacterial causes of diarrhea, accounting for an estimated 300,000–500,000 deaths each year, mostly in young children. There unfortunately is not yet a vaccine that can offer sustained, broad-based protection against ETEC. While most vaccine development effort has focused on plasmid-encoded finger-like ETEC adhesin structures known as colonization factors, additional effort is needed to identify conserved target antigens. Epidemiologic studies suggest that immune responses to uncharacterized, chromosomally encoded antigens could contribute to protection resulting from repeated infections. Earlier studies of immune responses to ETEC infection had identified a class of surface-expressed molecules known as autotransporters (AT). Therefore, available ETEC genome sequences were examined to identify conserved ETEC autotransporters not shared by the commensal E. coli HS strain, followed by studies of the immune response to these antigens, and tests of their utility as vaccine components. Two chromosomally encoded ATs, identified in ETEC, but not in HS, were found to be immunogenic and protective in an animal model, suggesting that conserved AT molecules contribute to protective immune responses that follow natural ETEC infection and offering new potential targets for vaccines