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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
This essay advocates that “theology” as “God-talk” is endemic to Jewish discourse throughout the ages. Jewish theology is a dialectic between prescriptive halakhah or law on one side, and descriptive aggadah or narration on the other side. While the term “theology” itself is usually taken to mean human talk about God, Jewish “theology” as the explication of God’s revealed word (dvar Adonai) means, as Abraham Joshua Heschel (the foremost 20th century Jewish theologian) put it, “God’s anthropology.” Thus Jewish theology is the explication of what Jews have accepted as revealed truth, namely, what God wants humans to know of God’s concern for them as evidenced in history, and what God wants humans to do in response to God’s concern for them.
Scientific quality and feasibility are part of ethics review by Institutional Review Boards (IRBs). Scientific Review Committees (SRCs) were proposed to facilitate this assessment by the Clinical and Translational Science Award (CTSA) SRC Consensus Group. This study assessed SRC feasibility and impact at CTSA-affiliated academic health centers (AHCs).
SRC implementation at 10 AHCs was assessed pre/post-intervention using quantitative and qualitative methods. Pre-intervention, four AHCs had no SRC, and six had at least one SRC needing modifications to better align with Consensus Group recommendations.
Facilitators of successful SRC implementation included broad-based communication, an external motivator, senior-level support, and committed SRC reviewers. Barriers included limited resources and staffing, variable local mandates, limited SRC authority, lack of anticipated benefit, and operational challenges. Research protocol quality did not differ significantly between study periods, but respondents suggested positive effects. During intervention, median total review duration did not lengthen for the 40% of protocols approved within 3 weeks. For the 60% under review after 3 weeks, review was lengthened primarily due to longer IRB review for SRC-reviewed protocols. Site interviews recommended designing locally effective SRC processes, building buy-in by communication or by mandate, allowing time for planning and sharing best practices, and connecting SRC and IRB procedures.
The CTSA SRC Consensus Group recommendations appear feasible. Although not conclusive in this relatively short initial implementation, sites perceived positive impact by SRCs on study quality. Optimal benefit will require local or federal mandate for implementation, adapting processes to local contexts, and employing SRC stipulations.
Luminous quasars are powered by accretion onto supermassive black holes. Such luminous quasars have been discovered up to the highest redshifts, z > 7. Here we discuss recent observations of the host galaxies of luminous quasars at z ≳ 6. We do not find a correlation between ongoing black hole growth and star-formation rate in the high redshift quasars, possibly indicating that black holes and their hosts do not co-evolve. We further show that even with high spatial resolution observations of the gas kinematics, dynamical mass estimates remain highly uncertain and should be used with caution.
Healthcare organizations are required to provide workers with respiratory protection (RP) to mitigate hazardous airborne inhalation exposures. This study sought to better identify gaps that exist between RP guidance and clinical practice to understand issues that would benefit from additional research or clarification.
This paper presents first chronological results for a Holocene marshland system from the southern part of the Danube-Tisza Interfluve. Radiocarbon (14C) ages were used to build age-depth models relying of probabilistic tools. Four models have been built: a linear one using dates gained via simple calibration, a P_Sequence model, fitting a polynomial function to calibrated dates; a Gamma_Sequence considering priori given and posterior accumulation rates have been constructed. As there was no significant difference between the mean values of individual models all seem suitable for establishing a reliable chronology despite differences in 95% CI ranges. While P_Sequence models underestimated SR, values calculated from the polynomial model were not significantly different from those of the G_Sequence. Based on multiproxy geochemical, sedimentological, paleoecological data the evolution of the system was reconstructed, covering a timespan of ca. 13,000 years starting from 12,000 BC and lasting until 1300 AD. Highest accumulation rates are dated to the Early Middle Ages from the 11th century. Several climate changes could have been identified which are present in other Hungarian and Western European records too, such as the 5b IRD event at ca. 5800 BC, a humid phase around 1600 BC, and a cool humid phase around the 6th century AD.
Recent studies suggest that sand can serve as a vehicle for exposure of humans to pathogens at beach sites, resulting in increased health risks. Sampling for microorganisms in sand should therefore be considered for inclusion in regulatory programmes aimed at protecting recreational beach users from infectious disease. Here, we review the literature on pathogen levels in beach sand, and their potential for affecting human health. In an effort to provide specific recommendations for sand sampling programmes, we outline published guidelines for beach monitoring programmes, which are currently focused exclusively on measuring microbial levels in water. We also provide background on spatial distribution and temporal characteristics of microbes in sand, as these factors influence sampling programmes. First steps toward establishing a sand sampling programme include identifying appropriate beach sites and use of initial sanitary assessments to refine site selection. A tiered approach is recommended for monitoring. This approach would include the analysis of samples from many sites for faecal indicator organisms and other conventional analytes, while testing for specific pathogens and unconventional indicators is reserved for high-risk sites. Given the diversity of microbes found in sand, studies are urgently needed to identify the most significant aetiological agent of disease and to relate microbial measurements in sand to human health risk.