The asymptotic regimes of tilted Bianchi II cosmologies

In this paper we give, for the first time, a complete description of the dynamics of tilted spatially homogeneous cosmologies of Bianchi type II. The source is assumed to be a perfect fluid with equation of state $p = (\gamma -1) \mu$, where $\gamma$ is a constant. We show that unless the perfect fluid is stiff, the tilt destabilizes the Kasner solutions, leading to a Mixmaster-like initial singularity, with the tilt being dynamically significant. At late times the tilt becomes dynamically negligible unless the equation of state parameter satisfies $\gamma > {10/7}$. We also find that the tilt does not destabilize the flat FL model, with the result that the presence of tilt increases the likelihood of intermediate isotropization

The roles of the general practitioner and sexual health centre in HIV testing:comparative insights and impact on HIV incidence rates in the Rotterdam area, the Netherlands - a cross-sectional population-based study

Background: Access to HIV testing is crucial for detection, linkage to treatment, and prevention. In less urbanised areas, reliance on general practitioners (GPs) for HIV testing is probable, as sexual health centres (SHC) are mostly located within urbanised areas. Limited insight into individuals undergoing HIV testing stems from sparse standard registration of demographics at GPs. This cross-sectional study aims (1) to assess and compare HIV testing at the GP and SHC, and (2) to assess population- and provider-specific HIV incidence. Methods: Individual HIV testing data of GPs and SHC were linked to population register data (aged ≥ 15 years, Rotterdam area, 2015–2019). We reported the proportion HIV tested, and compared GP and SHC testing rates with negative binomial generalised additive models. Data on new HIV diagnoses (2015–2019) from the Dutch HIV Monitoring Foundation relative to the population were used to assess HIV incidence. Results: The overall proportion HIV tested was 1.14% for all residents, ranging from 0.41% for ≥ 40-year-olds to 4.70% for Antilleans. The GP testing rate was generally higher than the SHC testing rate with an overall rate ratio (RR) of 1.61 (95% CI: 1.56–1.65), but not for 15-24-year-olds (RR: 0.81, 95% CI: 0.74–0.88). Large differences in HIV testing rate (1.36 to 39.47 per 1,000 residents) and GP-SHC ratio (RR: 0.23 to 7.24) by geographical area were observed. The GPs’ contribution in HIV testing was greater for GP in areas further away from the SHC. In general, population groups that are relatively often tested are also the groups with most diagnoses and highest incidence (e.g., men who have sex with men, non-western). The overall incidence was 10.55 per 100,000 residents, varying from 3.09 for heterosexual men/women to 24.04 for 25–29-year-olds. Conclusions: GPs have a pivotal role in HIV testing in less urbanised areas further away from the SHC, and among some population groups. A relatively high incidence often follows relatively high testing rates. Opportunities to improve HIV testing have been found for migrants, lower-educated individuals, in areas less urbanised areas and further away from GP/SHC. Strategies include additional targeted testing, via for example SHC branch locations and outreach activities.</p

Clinical and functional consequences of C-terminal variants in MCT8

CONTEXT: Genetic variants in SLC16A2, encoding the thyroid hormone transporter MCT8, can cause intellectual and motor disability and abnormal serum thyroid function tests, known as MCT8 deficiency. The C-terminal domain of MCT8 is poorly conserved, which complicates prediction of the deleteriousness of variants in this region. We studied the functional consequences of 5 novel variants within this domain and their relation to the clinical phenotypes. METHODS: We enrolled male subjects with intellectual disability in whom genetic variants were identified in exon 6 of SLC16A2. The impact of identified variants was evaluated in transiently transfected cell lines and patient-derived fibroblasts. RESULTS: Seven individuals from 5 families harbored potentially deleterious variants affecting the C-terminal domain of MCT8. Two boys with clinical features considered atypical for MCT8 deficiency had a missense variant [c.1724A>G;p.(His575Arg) or c.1796A>G;p.(Asn599Ser)] that did not affect MCT8 function in transfected cells or patient-derived fibroblasts, challenging a causal relationship. Two brothers with classical MCT8 deficiency had a truncating c.1695delT;p.(Val566*) variant that completely inactivated MCT8 in vitro. The 3 other boys had relatively less-severe clinical features and harbored frameshift variants that elongate the MCT8 protein [c.1805delT;p.(Leu602HisfsTer680) and c.del1826-1835;p.(Pro609GlnfsTer676)] and retained ~50% residual activity. Additional truncating variants within transmembrane domain 12 were fully inactivating, whereas those within the intracellular C-terminal tail were tolerated. CONCLUSIONS: Variants affecting the intracellular C-terminal tail of MCT8 are likely benign unless they cause frameshifts that elongate the MCT8 protein. These findings provide clinical guidance in the assessment of the pathogenicity of variants within the C-terminal domain of MCT8

Leprosy control: perspectives & epidemiological and operational aspects

OBJECTIVES: As a starting point, a vast variety of 200 technical papers and documents published during the ten years 1999-2008, from Brazilian and international organizations dedicated to the control of leprosy, was taken. A study was then undertaken to investigate its future evolutive possibilities by employing resources obtained from scenario analyses. DESIGN: The methodological reconstruction in use was of a qualitative nature, based on a bibliographic review and content analysis techniques. The latter were employed in a documental, categorical, contingent, frequency-based format, in compliance with appropriate and pertinent conditions. RESULTS: Nowadays, important elements on epidemiological and operational aspects have been regained, as well as respective perspectives. CONCLUSIONS: A projection is made towards the fact that the maintenance of the disease's present incidence levels constitute economic and sanitary challenges that confront issues ranging from the neoliberal model of global societal organization to specific competences of actions taken by health teams in the field

Cost-Effectiveness of Interventions to Prevent Disability in Leprosy: A Systematic Review

Background: Prevention of disability (POD) is one of the key objectives of leprosy programmes. Recently, coverage and access have been identified as the priority issues in POD. Assessing the cost-effectiveness of POD interventions is highly relevant to understanding the barriers and opportunities to achieving universal coverage and access with limited resources. The purpose of this study was to systematically review the quality of existing cost-effectiveness evidence and discuss implications for future research and strategies to prevent disability in leprosy and other disabling conditions. Methodology/Principal Findings: We searched electronic databases (NHS EED, MEDLINE, EMBASE, and LILACS) and databases of ongoing trials (www.controlled-trials.com/mrct/, www.who.int/trialsearch). We checked reference lists and contacted experts for further relevant studies. We included studies that reported both cost and effectiveness outcomes of two or more alternative interventions to prevent disability in leprosy. We assessed the quality of the identified studies using a standard checklist for critical appraisal of economic evaluations of health care programmes. We found 66 citations to potentially relevant studies and three met our criteria. Two were randomised controlled trials (footwear, management of neuritis) and one was a generic model-based study (cost per DALY). Generally, the studies were small in size, reported inadequately all relevant costs, uncertainties in estimates, and issues of concern and were based on limited data sources. No cost-effectiveness data on self-care, which is a key strategy in POD, was found. Conclusion/Significance: Evidence for cost-effectiveness of POD interventions for leprosy is scarce. High quality research is needed to identify POD interventions that offer value for money where resources are very scarce, and to develop strategies aimed at available, affordable and sustainable quality POD services for leprosy. The findings are relevant for other chronically disabling conditions, such as lymphatic filariasis, Buruli ulcer and diabetes in developing countries

Precision bond lengths for Rydberg Matter clusters KN (N = 19, 37, 61 and 91) in excitation levels n = 4 - 8 from rotational radio-frequency emission spectra

Clusters of the electronically excited condensed matter Rydberg Matter (RM) are planar and six-fold symmetric with magic numbers N = 7, 19, 37, 61 and 91. The bond distances in the clusters are known with a precision of +- 5% both from theory and Coulomb explosion experiments. Long series of up to 40 consecutive lines from rotational transitions in such clusters are now observed in emission in the radio-frequency range 7-90 MHz. The clusters are produced in five different vacuum chambers equipped with RM emitters. The most prominent series with B = 0.9292 +- 0.0001 MHz agrees accurately with expectation (within 2%) for the planar six-fold symmetric cluster K19 in excitation level n = 4. Other long series agree even better with K19 at n = 5 and 6. The ratio between the interatomic distance and the theoretical electron orbit radius (the dimensional ratio) for K19 in n = 4 is found to be 2.8470 +- 0.0003. For clusters K19 (n = 6) and K37 (n = 7 and 8) the dimensional ratio 2.90 is the highest value that is found, which happens to be exactly the theoretical value. Clusters K61 and K91 in n = 5 and 6 have slightly lower dimensional ratios. This is expected since the edge effects are smaller. Intensity alternations are observed of approximately 7:3. The nuclear spins interact strongly with the magnetic field from the orbiting electrons. Spin transitions are observed with energy differences corresponding accurately (within 0.6%) to transitions with apparent total (delta)F = -3 at excitation levels n = 5 and 6. The angular momentum coupling schemes in the clusters are complex but well understood.Comment: 37 pages, 14 figure

The Carboxy-Terminal Domain of Dictyostelium C-Module-Binding Factor Is an Independent Gene Regulatory Entity

The C-module-binding factor (CbfA) is a multidomain protein that belongs to the family of jumonji-type (JmjC) transcription regulators. In the social amoeba Dictyostelium discoideum, CbfA regulates gene expression during the unicellular growth phase and multicellular development. CbfA and a related D. discoideum CbfA-like protein, CbfB, share a paralogous domain arrangement that includes the JmjC domain, presumably a chromatin-remodeling activity, and two zinc finger-like (ZF) motifs. On the other hand, the CbfA and CbfB proteins have completely different carboxy-terminal domains, suggesting that the plasticity of such domains may have contributed to the adaptation of the CbfA-like transcription factors to the rapid genome evolution in the dictyostelid clade. To support this hypothesis we performed DNA microarray and real-time RT-PCR measurements and found that CbfA regulates at least 160 genes during the vegetative growth of D. discoideum cells. Functional annotation of these genes revealed that CbfA predominantly controls the expression of gene products involved in housekeeping functions, such as carbohydrate, purine nucleoside/nucleotide, and amino acid metabolism. The CbfA protein displays two different mechanisms of gene regulation. The expression of one set of CbfA-dependent genes requires at least the JmjC/ZF domain of the CbfA protein and thus may depend on chromatin modulation. Regulation of the larger group of genes, however, does not depend on the entire CbfA protein and requires only the carboxy-terminal domain of CbfA (CbfA-CTD). An AT-hook motif located in CbfA-CTD, which is known to mediate DNA binding to A+T-rich sequences in vitro, contributed to CbfA-CTD-dependent gene regulatory functions in vivo