A Small Target Neutrino Deep-Inelastic Scattering Experiment at the First Muon Collider

Several different scenarios for neutrino scattering experiments using a neutrino beam from the muon collider complex are discussed. The physics reach of a neutrino experiment at the front end of a muon collider is shown to extend far beyond that of current neutrino experiments, since the high intensity neutrino beams one would see at the muon collider allow for a large flexibility in choosing neutrino targets. Measurements of quark spin, A-dependence of the structure function $xF_3$ and neutral current chiral couplings to quarks are outlined.Comment: 7 pages, 2 figures, to appear in the proceedings of the Workshop on Physics at the First Muon Collider and at the Front End of a Muon Collider, November 1997, Fermila

Exploring the Impact of Targeted Distribution of Free Bed Nets on Households Bed Net Ownership, Socio-Economic Disparities and Childhood Malaria Infection Rates: Analysis of National Malaria Survey Data from three Sub-Saharan Africa countries.

The last decade has witnessed increased funding for malaria control. Malaria experts have used the opportunity to advocate for rollout of such interventions as free bed nets. A free bed net distribution strategy is seen as the quickest way to improve coverage of effective malaria control tools especially among poorest communities. Evidence to support this claim is however, sparse. This study explored the effectiveness of targeted free bed net distribution strategy in achieving equity in terms of ownership and use of bed nets and also reduction of malaria prevalence among children under-five years of age. National malaria indicator survey (MIS) data from Angola, Tanzania and Uganda was used in the analysis. Hierarchical multilevel logistic regression models were used to analyse the relationship between variables of interest. Outcome variables were defined as: childhood test-confirmed malaria infections, household ownership of any mosquito net and children's use of any mosquito nets. Marginal effects of having free bed net distribution on households with different wealth status were calculated. Angolan children from wealthier households were 6.4 percentage points less likely to be parasitaemic than those in poorest households, whereas those from Tanzania and Uganda were less likely to test malaria positive by 7 and 11.6 percentage points respectively (p < 0.001). The study estimates and present results on the marginal effects based on the impact of free bed net distribution on children's malaria status given their socio-economic background. Poorest households were less likely to own a net by 21.4% in Tanzania, and 2.8% in Uganda, whereas both poorer and wealthier Angolan households almost achieved parity in bed net ownership (p < 0.001). Wealthier households had a higher margin of using nets than poorest people in both Tanzania and Uganda by 11.4% and 3.9% respectively. However, the poorest household in Angola had a 6.1% net use advantage over children in wealthier households (p < 0.001). This is the first study to use nationally representative data to explore inequalities in bed net ownership and related consequences on childhood malaria infection rates across different countries. While targeted distribution of free bed nets improved overall bed net ownership, it did not overcome ownership inequalities as measured by household socioeconomic status. Use of bed nets was disproportionately lower among poorest children, except for Angola where bed net use was higher among poorest households when compared to children in wealthier households. The study highlights the need for malaria control world governing bodies and policy makers to continue working on finding appropriate strategies to improve access to effective malaria control tools especially by the poorest who often times bears the brunt of malaria burden than their wealthier counterparts

A Self-Lysis Pathway that Enhances the Virulence of a Pathogenic Bacterium

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of the alpA gene, which encodes a positive regulator that activates expression of the alpBCDE lysis cassette. Although this is lethal to the individual cell in which it occurs, we find it benefits the population as a whole during infection of a mammalian host. Thus, host and pathogen each may use PCD as a survival-promoting strategy. We suggest that activation of the Alp cell lysis pathway is a disease-enhancing response to bacterial DNA damage inflicted by the host immune system

The cost of mapping trachoma: Data from the Global Trachoma Mapping Project.

BACKGROUND: The Global Trachoma Mapping Project (GTMP) was implemented with the aim of completing the baseline map of trachoma globally. Over 2.6 million people were examined in 1,546 districts across 29 countries between December 2012 and January 2016. The aim of the analysis was to estimate the unit cost and to identify the key cost drivers of trachoma prevalence surveys conducted as part of GTMP. METHODOLOGY AND PRINCIPAL FINDINGS: In-country and global support costs were obtained using GTMP financial records. In-country expenditure was analysed for 1,164 districts across 17 countries. The mean survey cost was $13,113 per district [median:$11,675; IQR = $8,365-$14,618], $17,566 per evaluation unit [median:$15,839; IQR = $10,773-$19,915], $692 per cluster [median:$625; IQR = $452-$847] and $6.0 per person screened [median:$4.9; IQR = $3.7-$7.9]. Survey unit costs varied substantially across settings, and were driven by parameters such as geographic location, demographic characteristics, seasonal effects, and local operational constraints. Analysis by activities showed that fieldwork constituted the largest share of in-country survey costs (74%), followed by training of survey teams (11%). The main drivers of in-country survey costs were personnel (49%) and transportation (44%). Global support expenditure for all surveyed districts amounted to $5.1m, which included grant management, epidemiological support, and data stewardship. CONCLUSION: This study provides the most extensive analysis of the cost of conducting trachoma prevalence surveys to date. The findings can aid planning and budgeting for future trachoma surveys required to measure the impact of trachoma elimination activities. Furthermore, the results of this study can also be used as a cost basis for other disease mapping programmes, where disease or context-specific survey cost data are not available

The Public Health Leadership and Implementation Academy for Noncommunicable Diseases.

PURPOSE AND OBJECTIVES: Low- and middle-income countries (LMICs) have a large burden of noncommunicable diseases and confront leadership capacity challenges and gaps in implementation of proven interventions. To address these issues, we designed the Public Health Leadership and Implementation Academy (PH-LEADER) for noncommunicable diseases. The objective of this program evaluation was to assess the quality and effectiveness of PH-LEADER. INTERVENTION APPROACH: PH-LEADER was directed at midcareer public health professionals, researchers, and government public health workers from LMICs who were involved in prevention and control of noncommunicable diseases. The 1-year program focused on building implementation research and leadership capacity to address noncommunicable diseases and included 3 complementary components: a 2-month online preparation period, a 2-week summer course in the United States, and a 9-month, in-country, mentored project. EVALUATION METHODS: Four trainee groups participated from 2013 through 2016. We collected demographic information on all trainees and monitored project and program outputs. Among the 2015 and 2016 trainees, we assessed program satisfaction and pre-post program changes in leadership practices and the perceived competence of trainees for performing implementation research. RESULTS: Ninety professionals (mean age 38.8 years; 57% male) from 12 countries were trained over 4 years. Of these trainees, 50% were from India and 29% from Mexico. Trainees developed 53 projects and 9 publications. Among 2015 and 2016 trainees who completed evaluation surveys (n = 46 of 55), we saw pre-post training improvements in the frequency with which they acted as role models (Cohen's d = 0.62, P <.001), inspired a shared vision (d = 0.43, P =.005), challenged current processes (d = 0.60, P <.001), enabled others to act (d = 0.51, P =.001), and encouraged others by recognizing or celebrating their contributions and accomplishments (d = 0.49, P =.002). Through short on-site evaluation forms (scale of 1-10), trainees rated summer course sessions as useful (mean, 7.5; SD = 0.2), with very good content (mean, 8.5; SD = 0.6) and delivered by very good professors (mean, 8.6; SD = 0.6), though they highlighted areas for improvement. IMPLICATIONS FOR PUBLIC HEALTH: The PH-LEADER program is a promising strategy to build implementation research and leadership capacity to address noncommunicable diseases in LMICs

The Economic Benefits Resulting from the First 8 Years of the Global Programme to Eliminate Lymphatic Filariasis (2000–2007)

Lymphatic filariasis (LF), commonly known as ‘elephantiasis’, is one of the world's most debilitating infectious diseases. In 83 countries worldwide, more than 1.3 billion people are at risk of infection with an estimated 120 million individuals already infected. A recent publication reviewing the health impact of the first 8 years of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) demonstrated the enormous health benefits achieved in populations receiving annual mass drug administration (MDA), as a result of infection prevented, disease progression halted, and ancillary treatment of co-infections. To date, however, no studies have estimated the economic value of these health benefits, either to the individuals or the societies afflicted with LF. Our study estimates that US$21.8 billion will be gained among individuals benefitting from just the first 8 years of the Global Programme, and an additional US$2.2 billion will be saved by the health systems of endemic countries. Treating endemic populations is possible at very low cost – particularly because of the generous drug donations from two pharmaceutical companies – but results in enormous economic benefits. Findings from this study yield a much clearer understanding the GPELF's full economic impact and strengthen the conviction that it is a ‘best buy’ in global health

Justify your alpha

Benjamin et al. proposed changing the conventional “statistical significance” threshold (i.e.,the alpha level) from p ≤ .05 to p ≤ .005 for all novel claims with relatively low prior odds. They provided two arguments for why lowering the significance threshold would “immediately improve the reproducibility of scientific research.” First, a p-value near .05provides weak evidence for the alternative hypothesis. Second, under certain assumptions, an alpha of .05 leads to high false positive report probabilities (FPRP2 ; the probability that a significant finding is a false positive

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection