Triple-drug treatment is effective for lymphatic filariasis microfilaria clearance in Samoa

Following the first triple-drug mass drug administration (MDA) for lymphatic filariasis in Samoa in 2018, unexpected persistence of microfilaria (Mf) positivity in 18 (15%) of 121 antigen-positive persons was observed in a nationwide household survey 1–2 months later. Of the 18 Mf positive persons, 14 reported taking the MDA, raising concerns about MDA efficacy. In 2019, 5–6 months after the 2018 survey, a monitored treatment study was done to evaluate directly observed weight-based treatment in these Mf positive individuals. Mf presence and density were assessed before and 7 days after treatment, using 1 mL membrane filtered venous blood, and 60 uL thick blood films on slides prepared from venous or fingerprick blood. All 14 participants were still Mf positive on filters from venous blood pre-treatment samples, but two were negative by slide made from the same samples. Mf were cleared completely by day 7 in 12 of 13 participants followed up, and by day 30 in the remaining participant. Filtered blood using EDTA samples (to reduce clumping of Mf) is preferred over slides alone for improving the likelihood of detecting Mf and estimating their density. The triple-drug MDA strategy was effective at clearing Mf when given and taken at the correct dose

A new way to rapidly create functional, fluorescent fusion proteins: random insertion of GFP with an in vitro transposition reaction

BACKGROUND: The jellyfish green fluorescent protein (GFP) can be inserted into the middle of another protein to produce a functional, fluorescent fusion protein. Finding permissive sites for insertion, however, can be difficult. Here we describe a transposon-based approach for rapidly creating libraries of GFP fusion proteins. RESULTS: We tested our approach on the glutamate receptor subunit, GluR1, and the G protein subunit, α(s). All of the in-frame GFP insertions produced a fluorescent protein, consistent with the idea that GFP will fold and form a fluorophore when inserted into virtually any domain of another protein. Some of the proteins retained their signaling function, and the random nature of the transposition process revealed permissive sites for insertion that would not have been predicted on the basis of structural or functional models of how that protein works. CONCLUSION: This technique should greatly speed the discovery of functional fusion proteins, genetically encodable sensors, and optimized fluorescence resonance energy transfer pairs

Quantifying the utility of taking pills for preventing adverse health outcomes: a cross-sectional survey

ObjectivesThe utility value attributed to taking pills for prevention can have a major effect on the cost-effectiveness of interventions, but few published studies have systematically quantified this value. We sought to quantify the utility value of taking pills used for prevention of cardiovascular disease (CVD).DesignCross-sectional survey.SettingCentral North Carolina.Participants708 healthcare employees aged 18 years and older.Primary and secondary outcomesUtility values for taking 1 pill/day, assessed using time trade-off, modified standard gamble and willingness-to-pay methods.ResultsMean age of respondents was 43 years (19–74). The majority of the respondents were female (83%) and Caucasian (80%). Most (80%) took at least 2 pills/day. Mean utility values for taking 1 pill/day using the time trade-off method were: 0.9972 (95% CI 0.9962 to 0.9980). Values derived from the standard gamble and willingness-to-pay methods were 0.9967 (0.9954 to 0.9979) and 0.9989 (95% CI 0.9986 to 0.9991), respectively. Utility values varied little across characteristics such as age, sex, race, education level or number of pills taken per day.ConclusionsThe utility value of taking pills daily in order to prevent an adverse CVD health outcome is approximately 0.997

A community survey of coverage and adverse events following country-wide triple-drug mass drug administration for lymphatic filariasis elimination, Samoa 2018

The Global Programme to Eliminate Lymphatic Filariasis has made considerable progress but is experiencing challenges in meeting targets in some countries. Recent World Health Organization guidelines have recommended two rounds of triple-drug therapy with ivermectin, diethylcarbamazine (DEC), and albendazole (IDA), in areas where mass drug administration (MDA) results with two drugs (DEC and albendazole) have been suboptimal, as is the case in Samoa. In August 2018, Samoa was the first country in the world to implement countrywide triple-drug MDA. This paper aims to describe Samoa’s experience with program coverage and adverse events (AEs) in the first round of triple-drug MDA. We conducted a large cross-sectional community survey to assess MDA awareness, reach, compliance, coverage and AEs in September/October 2018, 7–11 weeks after the first round of triple-drug MDA. In our sample of 4420 people aged ≥2 years (2.2% of the population), age-adjusted estimates indicated that 89.0% of the eligible population were offered MDA, 83.9% of the eligible population took MDA (program coverage), and 80.2% of the total population took MDA (epidemiological coverage). Overall, 83.8% (2986/3563) reported that they did not feel unwell at all after taking MDA. Mild AEs (feeling unwell but able to do normal everyday things) were reported by 13.3% (476/3563) and moderate or severe AEs (feeling unwell and being unable to do normal everyday activities such as going to work or school) by 2.9% (103/3563) of participants. This study following the 2018 triple-drug MDA in Samoa demonstrated a high reported program awareness and reach of 90.8% and 89.0%, respectively. Age-adjusted program coverage of 83.9% of the total population showed that MDA was well accepted and well tolerated by the community

The resource theory of quantum reference frames: manipulations and monotones

Every restriction on quantum operations defines a resource theory, determining how quantum states that cannot be prepared under the restriction may be manipulated and used to circumvent the restriction. A superselection rule is a restriction that arises through the lack of a classical reference frame and the states that circumvent it (the resource) are quantum reference frames. We consider the resource theories that arise from three types of superselection rule, associated respectively with lacking: (i) a phase reference, (ii) a frame for chirality, and (iii) a frame for spatial orientation. Focussing on pure unipartite quantum states (and in some cases restricting our attention even further to subsets of these), we explore single-copy and asymptotic manipulations. In particular, we identify the necessary and sufficient conditions for a deterministic transformation between two resource states to be possible and, when these conditions are not met, the maximum probability with which the transformation can be achieved. We also determine when a particular transformation can be achieved reversibly in the limit of arbitrarily many copies and find the maximum rate of conversion. A comparison of the three resource theories demonstrates that the extent to which resources can be interconverted decreases as the strength of the restriction increases. Along the way, we introduce several measures of frameness and prove that these are monotonically nonincreasing under various classes of operations that are permitted by the superselection rule.Comment: 37 pages, 4 figures, Published Versio

Lymphatic filariasis epidemiology in Samoa in 2018: geographic clustering and higher antigen prevalence in older age groups

Background: Samoa conducted eight nationwide rounds of mass drug administration (MDA) for lymphatic filariasis (LF) between 1999 and 2011, and two targeted rounds in 2015 and 2017 in North West Upolu (NWU), one of three evaluation units (EUs). Transmission Assessment Surveys (TAS) were conducted in 2013 (failed in NWU) and 2017 (all three EUs failed). In 2018, Samoa was the first in the world to distribute nationwide triple-drug MDA using ivermectin, diethylcarbamazine, and albendazole. Surveillance and Monitoring to Eliminate LF and Scabies from Samoa (SaMELFS Samoa) is an operational research program designed to evaluate the effectiveness of triple-drug MDA on LF transmission and scabies prevalence in Samoa, and to compare the usefulness of different indicators of LF transmission. This paper reports results from the 2018 baseline survey and aims to i) investigate antigen (Ag) prevalence and spatial epidemiology, including geographic clustering; ii) compare Ag prevalence between two different age groups (5–9 years versus ≥10 years) as indicators of areas of ongoing transmission; and iii) assess the prevalence of limb lymphedema in those aged ≥15 years. Methods: A community-based cluster survey was conducted in 30 randomly selected and five purposively selected clusters (primary sampling units, PSUs), each comprising one or two villages. Participants were recruited through household surveys (age ≥5 years) and convenience surveys (age 5–9 years). Alere Filariasis Test Strips (FTS) were used to detect Ag, and prevalence was adjusted for survey design and standardized for age and gender. Adjusted Ag prevalence was estimated for each age group (5–9, ≥10, and all ages ≥5 years) for random and purposive PSUs, and by region. Intraclass correlation (ICC) was used to quantify clustering at regions, PSUs, and households. Results: A total of 3940 persons were included (1942 children aged 5–9 years, 1998 persons aged ≥10 years). Adjusted Ag prevalence in all ages ≥5 years in randomly and purposively selected PSUs were 4.0% (95% CI 2.8–5.6%) and 10.0% (95% CI 7.4–13.4%), respectively. In random PSUs, Ag prevalence was lower in those aged 5–9 years (1.3%, 95% CI 0.8–2.1%) than ≥10 years (4.7%, 95% CI 3.1–7.0%), and poorly correlated at the PSU level (R-square = 0.1459). Adjusted Ag prevalence in PSUs ranged from 0% to 10.3% (95% CI 5.9–17.6%) in randomly selected and 3.8% (95% CI 1.3–10.8%) to 20.0% (95% CI 15.3–25.8%) in purposively selected PSUs. ICC for Ag-positive individuals was higher at households (0.46) compared to PSUs (0.18) and regions (0.01). Conclusions: Our study confirmed ongoing transmission of LF in Samoa, in accordance with the 2017 TAS results. Ag prevalence varied significantly between PSUs, and there was poor correlation between prevalence in 5–9 year-olds and older ages, who had threefold higher prevalence. Sampling older age groups would provide more accurate estimates of overall prevalence, and be more sensitive for identifying residual hotspots. Higher prevalence in purposively selected PSUs shows local knowledge can help identify at least some hotspots

Changes in inferior vena cava area represent a more sensitive metric than changes in filling pressures during experimental manipulation of intravascular volume and tone

AIMS: Remote monitoring of pulmonary artery pressure has reduced heart failure (HF) hospitalizations in chronic HF as elevation of pulmonary artery pressure provides information that can guide treatment. The venous system is characterized by high capacitance, thus substantial increases in intravascular volume can occur before filling pressures increase. The inferior vena cava (IVC) is a highly compliant venous conduit and thus a candidate for early detection of change in intravascular volume. We aimed to compare IVC cross-sectional area using a novel sensor with cardiac filling pressures during experimental manipulation of volume status, vascular tone, and cardiac function. METHODS AND RESULTS: Experiments were conducted in sheep to manipulate volume status (colloid infusion), vascular tone (nitroglycerin infusion) and cardiac function (rapid cardiac pacing). A wireless implantable IVC sensor was validated ex-vivo and in-vivo, and then used to measure the cross-sectional area of the IVC. Right- and left-sided cardiac filling pressures were obtained via right heart catheterization. The IVC sensor provided highly accurate and precise measurements of cross-sectional area in ex-vivo and in-vivo validation. IVC area changes were more sensitive than the corresponding changes in cardiac filling pressures during colloid infusion (p < 0.001), vasodilatation (p < 0.001) and cardiac dysfunction induced by rapid pacing (p ≤ 0.02). CONCLUSIONS: Inferior vena cava area can be remotely and accurately measured in real time with a wireless implantable sensor. Changes in IVC area are more sensitive than corresponding changes in filling pressures following experimental volume loading and fluid redistribution. Additional research is warranted to understand if remote monitoring of the IVC may have advantages over pressure-based monitors in HF

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed