Monitoring trends in HIV prevalence among young people, aged 15 to 24 years, in Manicaland, Zimbabwe

BACKGROUND: In June 2001, the United Nations General Assembly Special Session (UNGASS) set a target of reducing HIV prevalence among young women and men, aged 15 to 24 years, by 25% in the worst-affected countries by 2005, and by 25% globally by 2010. We assessed progress toward this target in Manicaland, Zimbabwe, using repeated household-based population serosurvey data. We also validated the representativeness of surveillance data from young pregnant women, aged 15 to 24 years, attending antenatal care (ANC) clinics, which UNAIDS recommends for monitoring population HIV prevalence trends in this age group. Changes in socio-demographic characteristics and reported sexual behaviour are investigated. METHODS: Progress towards the UNGASS target was measured by calculating the proportional change in HIV prevalence among youth and young ANC attendees over three survey periods (round 1: 1998-2000; round 2: 2001-2003; and round 3: 2003-2005). The Z-score test was used to compare differences in trends between the two data sources. Characteristics of participants and trends in sexual risk behaviour were analyzed using Student's and two-tailed Z-score tests. RESULTS: HIV prevalence among youth in the general population declined by 50.7% (from 12.2% to 6.0%) from round 1 to 3. Intermediary trends showed a large decline from round 1 to 2 of 60.9% (from 12.2% to 4.8%), offset by an increase from round 2 to 3 of 26.0% (from 4.8% to 6.0%). Among young ANC attendees, the proportional decline in prevalence of 43.5% (from 17.9% to 10.1%) was similar to that in the population (test for differences in trend: p value = 0.488) although ANC data significantly underestimated the population prevalence decline from round 1 to 2 (test for difference in trend: p value = 0.003) and underestimated the increase from round 2 to 3 (test for difference in trend: p value = 0.012). Reductions in risk behaviour between rounds 1 and 2 may have been responsible for general population prevalence declines. CONCLUSIONS: In Manicaland, Zimbabwe, the 2005 UNGASS target to reduce HIV prevalence by 25% was achieved. However, most prevention gains occurred before 2003. ANC surveillance trends overall were an adequate indicator of trends in the population, although lags were observed. Behaviour data and socio-demographic characteristics of participants are needed to interpret ANC trends

Determination of the atmospheric lifetime and global warming potential of sulfur hexafluoride using a three-dimensional model

We have used the Whole Atmosphere Community Climate Model (WACCM), with an updated treatment of loss processes, to determine the atmospheric lifetime of sulfur hexafluoride (SF6). The model includes the following SF6 removal processes: photolysis, electron attachment and reaction with mesospheric metal atoms. The Sodankylä Ion Chemistry (SIC) model is incorporated into the standard version of WACCM to produce a new version with a detailed D region ion chemistry with cluster ions and negative ions. This is used to determine a latitude- and altitude-dependent scaling factor for the electron density in the standard WACCM in order to carry out multi-year SF6 simulations. The model gives a mean SF6 lifetime over an 11-year solar cycle (τ) of 1278 years (with a range from 1120 to 1475 years), which is much shorter than the currently widely used value of 3200 years, due to the larger contribution (97.4 %) of the modelled electron density to the total atmospheric loss. The loss of SF6 by reaction with mesospheric metal atoms (Na and K) is far too slow to affect the lifetime. We investigate how this shorter atmospheric lifetime impacts the use of SF6 to derive stratospheric age of air. The age of air derived from this shorter lifetime SF6 tracer is longer by 9 % in polar latitudes at 20 km compared to a passive SF6 tracer. We also present laboratory measurements of the infrared spectrum of SF6 and find good agreement with previous studies. We calculate the resulting radiative forcings and efficiencies to be, on average, very similar to those reported previously. Our values for the 20-, 100- and 500-year global warming potentials are 18 000, 23 800 and 31 300, respectively

Measurement of the antineutrino neutral-current elastic differential cross section

arXiv:1309.7257v1 [hep-ex

Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial

OBJECTIVE To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training. RESEARCH DESIGN AND METHODS This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (∼810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison. RESULTS Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s−1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, LV mass/volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (β = 0.132, P = 0.002) but did not improve with the MRP (β = 0.016, P = 0.731). CONCLUSIONS In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function

KIR-HLA interactions extend human CD8+ T cell lifespan in vivo

BACKGROUND. There is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell–mediated control of chronic viral infection and that these results are consistent with an increase in the CD8+ T cell lifespan due to iKIR-ligand interactions. Here, we tested this prediction and investigated whether iKIRs affect T cell lifespan in humans in vivo. METHODS. We used stable isotope labeling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections. RESULTS. We showed that an individual’s iKIR-ligand genotype was a significant determinant of CD8+ T cell lifespan: in individuals with 2 iKIR-ligand gene pairs, memory CD8+ T cells survived, on average, for 125 days; in individuals with 4 iKIR-ligand gene pairs, the memory CD8+ T cell lifespan doubled to 250 days. Additionally, we showed that this survival advantage was independent of iKIR expression by the T cell of interest and, further, that the iKIR-ligand genotype altered the CD8+ and CD4+ T cell immune aging phenotype. CONCLUSIONS. Together, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival

Impact of Previously Unrecognized HLA Mismatches Using Ultrahigh Resolution Typing in Unrelated Donor Hematopoietic Cell Transplantation

PURPOSE: Ultrahigh resolution (UHR) HLA matching is reported to result in better outcomes following unrelated donor hematopoietic cell transplantation, improving survival and reducing post-transplant complications. However, most studies included relatively small numbers of patients. Here we report the findings from a large, multicenter validation study. METHODS: UHR HLA typing was available on 5,140 conventionally 10 out of 10 HLA-matched patients with malignant disease transplanted between 2008 and 2017. RESULTS: After UHR HLA typing, 82% of pairs remained 10 out of 10 UHR-matched; 12.3% of patients were 12 out of 12 UHR HLA-matched. Compared with 12 out of 12 UHR-matched patients, probabilities of grade 2-4 acute graft-versus-host disease (aGVHD) were significantly increased with UHR mismatches (overall P = .0019) and in those patients who were HLA-DPB1 T-cell epitope permissively mismatched or nonpermissively mismatched (overall P = .0011). In the T-cell-depleted subset, the degree of UHR HLA mismatch was only associated with increased transplant-related mortality (TRM) (overall P = .0068). In the T-cell-replete subset, UHR HLA matching was associated with a lower probability of aGVHD (overall P = .0020); 12 out of 12 UHR matching was associated with reduced TRM risk when compared with HLA-DPB1 T-cell epitope permissively mismatched patients, whereas nonpermissive mismatching resulted in a greater risk (overall P = .0003). CONCLUSION: This study did not confirm that UHR 12 out of 12 HLA matching increases the probability of overall survival but does demonstrate that aGVHD risk, and in certain settings TRM, is lowest in UHR HLA-matched pairs and thus warrants consideration when multiple 10 out of 10 HLA-matched donors of equivalent age are available

KIR-HLA interactions extend human CD8+ T cell lifespan in vivo.

BACKGROUND: There is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell-mediated control of chronic virus infection and that these results are consistent with an increase in CD8+ T cell lifespan due to iKIR-ligand interactions. Here we test this prediction and investigate whether iKIRs affect T cell lifespan in humans in vivo. METHODS: We used stable isotope labelling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections. RESULTS: We showed that an individual's iKIR-ligand genotype is a significant determinant of CD8+ T cell lifespan: in individuals with two iKIR-ligand gene pairs, memory CD8+ T cells survived on average for 125 days, in individuals with four iKIR-ligand gene pairs then memory CD8+ T cell lifespan was doubled to 250 days. Additionally, we showed that this survival advantage is independent of iKIR expression by the T cell of interest and further that iKIR-ligand genotype altered CD8+ and CD4+ T cell immune aging phenotype. CONCLUSIONS: Together these data reveal an unexpectedly large impact of iKIR genotype on T cell survival. FUNDING: Wellcome Trust, Medical Research Council, EU Horizon 2020, EU FP7, Leukemia and Lymphoma Research, National Institute of Health Research Imperial Biomedical Research Centre, Imperial College Research Fellowship, National Institute of Health, Jefferiss Trust

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

Estimating Distribution of Hidden Objects with Drones: From Tennis Balls to Manatees

Unmanned aerial vehicles (UAV), or drones, have been used widely in military applications, but more recently civilian applications have emerged (e.g., wildlife population monitoring, traffic monitoring, law enforcement, oil and gas pipeline threat detection). UAV can have several advantages over manned aircraft for wildlife surveys, including reduced ecological footprint, increased safety, and the ability to collect high-resolution geo-referenced imagery that can document the presence of species without the use of a human observer. We illustrate how geo-referenced data collected with UAV technology in combination with recently developed statistical models can improve our ability to estimate the distribution of organisms. To demonstrate the efficacy of this methodology, we conducted an experiment in which tennis balls were used as surrogates of organisms to be surveyed. We used a UAV to collect images of an experimental field with a known number of tennis balls, each of which had a certain probability of being hidden. We then applied spatially explicit occupancy models to estimate the number of balls and created precise distribution maps. We conducted three consecutive surveys over the experimental field and estimated the total number of balls to be 328 (95%CI: 312, 348). The true number was 329 balls, but simple counts based on the UAV pictures would have led to a total maximum count of 284. The distribution of the balls in the field followed a simulated environmental gradient. We also were able to accurately estimate the relationship between the gradient and the distribution of balls. Our experiment demonstrates how this technology can be used to create precise distribution maps in which discrete regions of the study area are assigned a probability of presence of an object. Finally, we discuss the applicability and relevance of this experimental study to the case study of Florida manatee distribution at power plants

Variational Methods for Biomolecular Modeling

Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the identification of essential energetic components, the optimal parametrization of energies, and the efficient computational implementation of energy variation or minimization. Given the fact that complex biomolecular systems are structurally non-uniform and their interactions occur through contact interfaces, their free energies are associated with various interfaces as well, such as solute-solvent interface, molecular binding interface, lipid domain interface, and membrane surfaces. This fact motivates the inclusion of interface geometry, particular its curvatures, to the parametrization of free energies. Applications of such interface geometry based energetic variational principles are illustrated through three concrete topics: the multiscale modeling of biomolecular electrostatics and solvation that includes the curvature energy of the molecular surface, the formation of microdomains on lipid membrane due to the geometric and molecular mechanics at the lipid interface, and the mean curvature driven protein localization on membrane surfaces. By further implicitly representing the interface using a phase field function over the entire domain, one can simulate the dynamics of the interface and the corresponding energy variation by evolving the phase field function, achieving significant reduction of the number of degrees of freedom and computational complexity. Strategies for improving the efficiency of computational implementations and for extending applications to coarse-graining or multiscale molecular simulations are outlined.Comment: 36 page