Lack of a significant legacy effect of baseline blood pressure 'treatment naivety' on all-cause and cardiovascular mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

Objectives: To investigate legacy effects at 14-year follow-up of all-cause and cardiovascular disease (CVD) mortality in 'treatment-naive' or 'previous treatment' groups based on blood pressure (BP)-lowering treatment status at baseline. Methods: A post-hoc observational study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We excluded participants with a previous history of CVD events. Cox proportional hazard model and 95% confidence interval were used to estimate the effects of treatment naive on mortality outcomes. Moreover, a subgroup analysis by estimated 10-year Framingham risk score was performed. Results: In multivariable models adjusting for baseline and in-trial characteristics (BP values and number of BP medications as time-dependent variables), there was no statistically significant difference in 5 and 14-year all-cause mortality with a hazard ratio of 0.93 (95% confidence interval 0.80-1.09) and hazard ratio 0.95 (0.88-1.03) and in 5 and 14-year CVD mortality hazard ratio 0.94 (0.72-1.23) and hazard ratio 0.93 (0.80-1.08). In subgroup by absolute CVD risk, no heterogeneity of the association between treatment naive and short-term or long-term all-cause or CVD mortality were found. All comparisons are between the treatment-naive and previous treatment groups. Conclusion: Physicians are concerned about 'legacy effects' of not treating individuals with a BP of 140 mmHg or over and low absolute risk. When treatment intensification was taken into consideration in the primary prevention population in this study, no adverse legacy effect as a result of baseline BP 'treatment naivety' was evident in 14 years of follow-up. The nonsignificant associations were consistent across the CVD risk subgroups. However, the results may be biased due to unobserved residual confounding and therefore should be interpreted with caution

DNA Methylation Analysis Reveals Distinct Methylation Signatures in Pediatric Germ Cell Tumors

Background: Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. Methods: We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Results: Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q \u3c 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Conclusion: Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy

Insecticide-treated net effectiveness at preventing Plasmodium falciparum infection varies by age and season

Abstract Background After increasing coverage of malaria interventions, malaria prevalence remains high in Malawi. Previous studies focus on the impact of malaria interventions among children under 5 years old. However, in Malawi, the prevalence of infection is highest in school-aged children (SAC), ages 5 to 15 years. This study examined the interaction between age group and insecticide-treated net (ITN) use for preventing individual and community-level infection in Malawi. Methods Six cross-sectional surveys were conducted in the rainy and dry seasons in southern Malawi from 2012 to 2014. Data were collected on household ITN usage and demographics. Blood samples for detection of Plasmodium falciparum infection were obtained from all household members present and over 6 months of age. Generalized linear mixed models were used to account for clustering at the household and community level. Results There were 17,538 observations from six surveys. The association between ITN use and infection varied by season in SAC, but not in other age groups. The adjusted odds ratio (OR) for infection comparing ITN users to non-users among SAC in the rainy season and dry season was 0.78 (95% CI 0.56, 1.10) and 0.51 (0.35, 0.74), respectively. The effect of ITN use did not differ between children under five and adults. Among all non-SACs the OR for infection was 0.78 (0.64, 0.95) in those who used ITNs compared to those that did not. Community net use did not protect against infection. Conclusions Protection against infection with ITN use varies by age group and season. Individual estimates of protection are moderate and a community-level effect was not detected. Additional interventions to decrease malaria prevalence are needed in Malawi.http://deepblue.lib.umich.edu/bitstream/2027.42/135726/1/12936_2017_Article_1686.pd

Bed net use among school-aged children after a universal bed net campaign in Malawi

Abstract Background Recent data from Malawi suggest that school-aged children (SAC), aged 5–15 years, have the highest prevalence of Plasmodium falciparum infection among all age groups. They are the least likely group to utilize insecticide-treated nets (ITNs), the most commonly available intervention to prevent malaria in Africa. This study examined the effects of a universal ITN distribution campaign, and their durability over time in SAC in Malawi. This study identified factors that influence net usage among SAC and how these factors changed over time. Methods Cross-sectional surveys using cluster random sampling were conducted at the end of each rainy and dry season in southern Malawi from 2012 to 2014; six surveys were done in total. Mass net distribution occurred between the first and second surveys. Data were collected on household and individual net usage as well as demographic information. Statistical analyses used generalized linear mixed models to account for clustering at the household and neighbourhood level. Results There were 7347 observations from SAC and 14,785 from young children and adults. SAC used nets significantly less frequently than the rest of the population (odds ratio (OR) from 0.14 to 0.38). The most important predictors of net usage among SAC were a lower ratio of people to nets in a household and higher proportion of nets that were hanging at the time of survey. Older SAC (11–15 years) were significantly less likely to use nets than younger SAC (5–10 years) [OR = 0.24 (95 % CI: 0.21, 0.28)]. The universal bed net campaign led to a statistically significant population-wide increase in net use, however net use returned to near baseline within 3 years. Conclusions This study suggests that a single universal net distribution campaign, in combination with routine distribution through health clinics is not sufficient to cause a sustained increase in net usage among SAC. Novel approaches to ITN distribution, such as school-based distribution, may be needed to address the high prevalence of infection in SAC.http://deepblue.lib.umich.edu/bitstream/2027.42/134523/1/12936_2016_Article_1178.pd

Generalised Framework for Controlling and Understanding Ion Dynamics with Passivated Lead Halide Perovskites

Metal halide perovskite solar cells have gained widespread attention due to their high efficiency and high defect tolerance. The absorbing perovskite layer is as a mixed electron-ion conductor that supports high rates of ion and charge transport at room temperature, but the migration of mobile defects can lead to degradation pathways. We combine experimental observations and drift-diffusion modelling to demonstrate a new framework to interpret surface photovoltage (SPV) measurements in perovskite systems and mixed electronic ionic conductors more generally. We conclude that the SPV in mixed electronic ionic conductors can be understood in terms of the change in electric potential at the surface associated with changes in the net charge within the semiconductor system. We show that by modifying the interfaces of perovskite bilayers, we may control defect migration behaviour throughout the perovskite bulk. Our new framework for SPV has broad implications for developing strategies to improve the stability of perovskite devices by controlling defect accumulation at interfaces. More generally, in mixed electronic conductors our framework provides new insights into the behaviour of mobile defects and their interaction with photoinduced charges, which are foundational to physical mechanisms in memristivity, logic, impedance, sensors and energy storage

Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo

Background and purpose Late infections after total hip arthroplasty are still a problem. Treatment procedures include resection arthroplasty with implantation of antibiotic-loaded beads or implantation of an antibiotic-impreganted spacer. However, little is known about antibiotic elution from bone cement beyond the first 2–3 postoperative days in humans

The value and opportunities of community-and citizen-based approaches to tropical forest biodiversity monitoring

The biodiversity sourcebook is accessible in pdf format for free from:•GOFC-GOLD Land Cover Office website: http://www.gofcgold.wur.nl/sites/gofcgold-geobon_biodiversitysourcebook.php•GEO BON website:http://geobon.org

Precise Black Hole Masses From Megamaser Disks: Black Hole-Bulge Relations at Low Mass

The black hole (BH)-bulge correlations have greatly influenced the last decade of effort to understand galaxy evolution. Current knowledge of these correlations is limited predominantly to high BH masses (M_BH> 10^8 M_sun) that can be measured using direct stellar, gas, and maser kinematics. These objects, however, do not represent the demographics of more typical L< L* galaxies. This study transcends prior limitations to probe BHs that are an order of magnitude lower in mass, using BH mass measurements derived from the dynamics of H_2O megamasers in circumnuclear disks. The masers trace the Keplerian rotation of circumnuclear molecular disks starting at radii of a few tenths of a pc from the central BH. Modeling of the rotation curves, presented by Kuo et al. (2010), yields BH masses with exquisite precision. We present stellar velocity dispersion measurements for a sample of nine megamaser disk galaxies based on long-slit observations using the B&C spectrograph on the Dupont telescope and the DIS spectrograph on the 3.5m telescope at Apache Point. We also perform bulge-to-disk decomposition of a subset of five of these galaxies with SDSS imaging. The maser galaxies as a group fall below the M_BH-sigma* relation defined by elliptical galaxies. We show, now with very precise BH mass measurements, that the low-scatter power-law relation between M_BH and sigma* seen in elliptical galaxies is not universal. The elliptical galaxy M_BH-sigma* relation cannot be used to derive the BH mass function at low mass or the zeropoint for active BH masses. The processes (perhaps BH self-regulation or minor merging) that operate at higher mass have not effectively established an M_BH-sigma* relation in this low-mass regime.Comment: 21 pages, 14 figures, accepted for publication in the Astrophysical Journa

The effect of glycol side chains on the assembly and microstructure of conjugated polymers

Conjugated polymers with glycol-based chains, are emerging as a material class with promising applications as organic mixed ionic-electronic conductors, particularly in bioelectronics and thermoelectrics. However, little is still known about their microstructure and the role of the side chains in determining intermolecular interactions and polymer packing. Here, we use the combination of electrospray deposition and scanning tunneling microscopy to determine the microstructure of prototypical glycolated conjugated polymers (pgBTTT and p(g2T-TT)) with submonomer resolution. Molecular dynamics simulations of the same surface-adsorbed polymers exhibit an excellent agreement with the experimental images, allowing us to extend the characterization of the polymers to the atomic scale. Our results prove that, similarly to their alkylated counterparts, glycolated polymers assemble through interdigitation of their side chains, although significant differences are found in their conformation and interaction patterns. A model is proposed that identifies the driving force for the polymer assembly in the tendency of the side chains to adopt the conformation of their free analogues, i.e., polyethylene and polyethylene glycol, for alkyl or ethylene glycol side chains, respectively. For both classes of polymers, it is also demonstrated that the backbone conformation is determined to a higher degree by the interaction between the side chains rather than by the backbone torsional potential energy. The generalization of these findings from two-dimensional (2D) monolayers to three-dimensional thin films is discussed, together with the opportunity to use this type of 2D study to gain so far inaccessible, subnm-scale information on the microstructure of conjugated polymers

A dexamethasone prodrug reduces the renal macrophage response and provides enhanced resolution of established murine lupus nephritis

We evaluated the ability of a macromolecular prodrug of dexamethasone (P-Dex) to treat lupus nephritis in (NZB × NZW)F1 mice. We also explored the mechanism underlying the anti-inflammatory effects of this prodrug. P-Dex eliminated albuminuria in most (NZB × NZW)F1 mice. Furthermore, P-Dex reduced the incidence of severe nephritis and extended lifespan in these mice. P-Dex treatment also prevented the development of lupus-associated hypertension and vasculitis. Although P-Dex did not reduce serum levels of anti-dsDNA antibodies or glomerular immune complexes, P-Dex reduced macrophage recruitment to the kidney and attenuated tubulointerstitial injury. In contrast to what was observed with free dexamethasone, P-Dex did not induce any deterioration of bone quality. However, P-Dex did lead to reduced peripheral white blood cell counts and adrenal gland atrophy. These results suggest that P-Dex is more effective and less toxic than free dexamethasone for the treatment of lupus nephritis in (NZB × NZW)F1 mice. Furthermore, the data suggest that P-Dex may treat nephritis by attenuating the renal inflammatory response to immune complexes, leading to decreased immune cell infiltration and diminished renal inflammation and injury