If I Ever Cry, You\u27ll Never Know

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Reduced acquisition and reactivation of human papillomavirus infections among older women treated with cryotherapy: results from a randomized trial in South Africa

<p>Abstract</p> <p>Background</p> <p>Treatment of women for high-grade cervical cancer precursors frequently results in clearance of the associated high-risk human papillomavirus (hrHPV) infection but the role of treatment among women without hrHPV is unknown. We investigated whether cervical cryotherapy reduces newly detected hrHPV infections among HIV-positive and HIV-negative women who were hrHPV negative when treated.</p> <p>Methods</p> <p>The impact of cryotherapy on newly detected hrHPV infections was examined among 612 women of known HIV serostatus, aged 35 to 65 years, who were negative for hrHPV DNA, and randomized to either undergo cryotherapy (n = 309) or not (n = 303). All women underwent repeat hrHPV DNA testing 6, 12, 24, and 36 months later.</p> <p>Results</p> <p>Among 540 HIV-negative women, cryotherapy was associated with a significant reduction in newly detected hrHPV infections. Women in the cryotherapy group were 55% less likely to have newly detected hrHPV than women in the control group (95% CI 0.28 to 0.71). This association was independent of the influence of changes in sexual behaviors following therapy (adjusted hazards ratio (HR) = 0.49, 95% CI 0.29 to 0.81). Among 72 HIV-positive women, similar reductions were not observed (HR = 1.10, 95% CI 0.53 to 2.29).</p> <p>Conclusions</p> <p>Cervical cryotherapy significantly reduced newly detected hrHPV infections among HIV-negative, but not HIV-positive women. These results raise intriguing questions about immunological responses and biological mechanisms underlying the apparent prophylactic benefits of cryotherapy.</p

Drd4 gene polymorphisms are associated with personality variation in a passerine bird

Polymorphisms in several neurotransmitter-associated genes have been associated with variation in human personality traits. Among the more promising of such associations is that between the human dopamine receptor D4 gene (Drd4) variants and novelty-seeking behaviour. However, genetic epistasis, genotype–environment interactions and confounding environmental factors all act to obscure genotype–personality relationships. Such problems can be addressed by measuring personality under standardized conditions and by selection experiments, with both approaches only feasible with non-human animals. Looking for similar Drd4 genotype–personality associations in a free-living bird, the great tit (Parus major), we detected 73 polymorphisms (66 SNPs, 7 indels) in the P. major Drd4 orthologue. Two of the P. major Drd4 gene polymorphisms were investigated for evidence of association with novelty-seeking behaviour: a coding region synonymous single nucleotide polymorphism (SNP830) and a 15 bp indel (ID15) located 5′ to the putative transcription initiation site. Frequencies of the three Drd4 SNP830 genotypes, but not the ID15 genotypes, differed significantly between two P. major lines selected over four generations for divergent levels of ‘early exploratory behaviour’ (EEB). Strong corroborating evidence for the significance of this finding comes from the analysis of free-living, unselected birds where we found a significant association between SNP830 genotypes and differing mean EEB levels. These findings suggest that an association between Drd4 gene polymorphisms and animal personality variation predates the divergence of the avian and mammalian lineages. Furthermore, this work heralds the possibility of following microevolutionary changes in frequencies of behaviourally relevant Drd4 polymorphisms within populations where natural selection acts differentially on different personality types

Morph-dependent fitness and directional change of morph frequencies over time in a Dutch population of Common buzzards <i>Buteo buteo</i>

How genetic polymorphisms are maintained in a population is a key question in evolutionary ecology. Previous work on a plumage colour polymorphism in the common buzzard Buteo buteo suggested heterozygote advantage as the mechanism maintaining the co-existence of three morphs (light, intermediate and dark). We took advantage of 20 years of life history data collected in a Dutch population to replicate earlier studies on the relationship between colour morph and fitness in this species. We examined differences between morphs in adult apparent survival, breeding success, annual number of fledglings produced and cumulative reproductive success. We found that cumulative reproductive success differed among morphs, with the intermediate morph having highest fitness. We also found assortative mating for colour morph, whereby assortative pairs were more likely to produce offspring and had longer-lasting pair bonds than disassortative pairs. Over the 20-year study period, the proportion of individuals with an intermediate morph increased. This apparent evolutionary change did not just arise from selection on individual phenotypes, but also from fitness benefits of assortative mating. The increased frequency of intermediates might also be due to immigration or drift. We hypothesize that genetic variation is maintained through spatial variation in selection pressures. Further studies should investigate morph-dependent dispersal behaviour and habitat choice

Hospital mortality is associated with ICU admission time

Previous studies have shown that patients admitted to the intensive care unit (ICU) after "office hours" are more likely to die. However these results have been challenged by numerous other studies. We therefore analysed this possible relationship between ICU admission time and in-hospital mortality in The Netherlands. This article relates time of ICU admission to hospital mortality for all patients who were included in the Dutch national ICU registry (National Intensive Care Evaluation, NICE) from 2002 to 2008. We defined office hours as 08:00-22:00 hours during weekdays and 09:00-18:00 hours during weekend days. The weekend was defined as from Saturday 00:00 hours until Sunday 24:00 hours. We corrected hospital mortality for illness severity at admission using Acute Physiology and Chronic Health Evaluation II (APACHE II) score, reason for admission, admission type, age and gender. A total of 149,894 patients were included in this analysis. The relative risk (RR) for mortality outside office hours was 1.059 (1.031-1.088). Mortality varied with time but was consistently higher than expected during "off hours" and lower during office hours. There was no significant difference in mortality between different weekdays of Monday to Thursday, but mortality increased slightly on Friday (RR 1.046; 1.001-1.092). During the weekend the RR was 1.103 (1.071-1.136) in comparison with the rest of the week. Hospital mortality in The Netherlands appears to be increased outside office hours and during the weekends, even when corrected for illness severity at admission. However, incomplete adjustment for certain confounders might still play an important role. Further research is needed to fully explain this differenc

Design, rationale, and baseline characteristics of a cluster randomized controlled trial of pay for performance for hypertension treatment: study protocol

<p>Abstract</p> <p>Background</p> <p>Despite compelling evidence of the benefits of treatment and well-accepted guidelines for treatment, hypertension is controlled in less than one-half of United States citizens.</p> <p>Methods/design</p> <p>This randomized controlled trial tests whether explicit financial incentives promote the translation of guideline-recommended care for hypertension into clinical practice and improve blood pressure (BP) control in the primary care setting. Using constrained randomization, we assigned 12 Veterans Affairs hospital outpatient clinics to four study arms: physician-level incentive; group-level incentive; combination of physician and group incentives; and no incentives (control). All participants at the hospital (cluster) were assigned to the same study arm. We enrolled 83 full-time primary care physicians and 42 non-physician personnel. The intervention consisted of an educational session about guideline-recommended care for hypertension, five audit and feedback reports, and five disbursements of incentive payments. Incentive payments rewarded participants for chart-documented use of guideline-recommended antihypertensive medications, BP control, and appropriate responses to uncontrolled BP during a prior four-month performance period over the 20-month intervention. To identify potential unintended consequences of the incentives, the study team interviewed study participants, as well as non-participant primary care personnel and leadership at study sites. Chart reviews included data collection on quality measures not related to hypertension. To evaluate the persistence of the effect of the incentives, the study design includes a washout period.</p> <p>Discussion</p> <p>We briefly describe the rationale for the interventions being studied, as well as the major design choices. Rigorous research designs such as the one described here are necessary to determine whether performance-based payment arrangements such as financial incentives result in meaningful quality improvements.</p> <p>Trial Registration</p> <p><url>http://www.clinicaltrials.gov</url><a href="http://www.clinicaltrials.gov/ct2/show/NCT00302718">NCT00302718</a></p

BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function

Podocyte loss and changes to the complex morphology are major causes of chronic kidney disease (CKD). As the incidence is continuously increasing over the last decades without sufficient treatment, it is important to find predicting biomarkers. Therefore, we measured urinary mRNA levels of podocyte genes NPHS1, NPHS2, PODXL and BDNF, KIM-1, CTSL by qRT-PCR of 120 CKD patients. We showed a strong correlation between BDNF and the kidney injury marker KIM-1, which were also correlated with NPHS1, suggesting podocytes as a contributing source. In human biopsies, BDNF was localized in the cell body and major processes of podocytes. In glomeruli of diabetic nephropathy patients, we found a strong BDNF signal in the remaining podocytes. An inhibition of the BDNF receptor TrkB resulted in enhanced podocyte dedifferentiation. The knockdown of the orthologue resulted in pericardial oedema formation and lowered viability of zebrafish larvae. We found an enlarged Bowman's space, dilated glomerular capillaries, podocyte loss and an impaired glomerular filtration. We demonstrated that BDNF is essential for glomerular development, morphology and function and the expression of BDNF and KIM-1 is highly correlated in urine cells of CKD patients. Therefore, BDNF mRNA in urine cells could serve as a potential CKD biomarker

ReSurveyGermany: Vegetation-plot time-series over the past hundred years in Germany

Vegetation-plot resurvey data are a main source of information on terrestrial biodiversity change, with records reaching back more than one century. Although more and more data from re-sampled plots have been published, there is not yet a comprehensive open-access dataset available for analysis. Here, we compiled and harmonised vegetation-plot resurvey data from Germany covering almost 100 years. We show the distribution of the plot data in space, time and across habitat types of the European Nature Information System (EUNIS). In addition, we include metadata on geographic location, plot size and vegetation structure. The data allow temporal biodiversity change to be assessed at the community scale, reaching back further into the past than most comparable data yet available. They also enable tracking changes in the incidence and distribution of individual species across Germany. In summary, the data come at a level of detail that holds promise for broadening our understanding of the mechanisms and drivers behind plant diversity change over the last century

A “Coiled-Coil” Motif Is Important for Oligomerization and DNA Binding Properties of Human Cytomegalovirus Protein UL77

Human cytomegalovirus (HCMV) UL77 gene encodes the essential protein UL77, its function is characterized in the present study. Immunoprecipitation identified monomeric and oligomeric pUL77 in HCMV infected cells. Immunostaining of purified virions and subviral fractions showed that pUL77 is a structural protein associated with capsids. In silico analysis revealed the presence of a coiled-coil motif (CCM) at the N-terminus of pUL77. Chemical cross-linking of either wild-type pUL77 or CCM deletion mutant (pUL77ΔCCM) implicated that CCM is critical for oligomerization of pUL77. Furthermore, co-immunoprecipitations of infected and transfected cells demonstrated that pUL77 interacts with the capsid-associated DNA packaging motor components, pUL56 and pUL104, as well as the major capsid protein. The ability of pUL77 to bind dsDNA was shown by an in vitro assay. Binding to certain DNA was further confirmed by an assay using biotinylated 36-, 250-, 500-, 1000-meric dsDNA and 966-meric HCMV-specific dsDNA designed for this study. The binding efficiency (BE) was determined by image processing program defining values above 1.0 as positive. While the BE of the pUL56 binding to the 36-mer bio-pac1 containing a packaging signal was 10.0±0.63, the one for pUL77 was only 0.2±0.03. In contrast to this observation the BE of pUL77 binding to bio-500 bp or bio-1000 bp was 2.2±0.41 and 4.9±0.71, respectively. By using pUL77ΔCCM it was demonstrated that this protein could not bind to dsDNA. These data indicated that pUL77 (i) could form homodimers, (ii) CCM of pUL77 is crucial for oligomerization and (iii) could bind to dsDNA in a sequence independent manner

The 2020 UV emitter roadmap

Solid state UV emitters have many advantages over conventional UV sources. The (Al,In,Ga)N material system is best suited to produce LEDs and laser diodes from 400 nm down to 210 nm—due to its large and tuneable direct band gap, n- and p-doping capability up to the largest bandgap material AlN and a growth and fabrication technology compatible with the current visible InGaN-based LED production. However AlGaN based UV-emitters still suffer from numerous challenges compared to their visible counterparts that become most obvious by consideration of their light output power, operation voltage and long term stability. Most of these challenges are related to the large bandgap of the materials. However, the development since the first realization of UV electroluminescence in the 1970s shows that an improvement in understanding and technology allows the performance of UV emitters to be pushed far beyond the current state. One example is the very recent realization of edge emitting laser diodes emitting in the UVC at 271.8 nm and in the UVB spectral range at 298 nm. This roadmap summarizes the current state of the art for the most important aspects of UV emitters, their challenges and provides an outlook for future developments