Farming is a high-pressure occupation. Populations of farmers face significant health risks, including injury, mental illness, and in some cases, heavy alcohol use. However, there is little research ...on farmers' use of substances beyond alcohol. This study examines factors relating to Irish farmers' disordered alcohol and substance use.
In accordance with STROBE guidelines for cross-sectional research and reporting, we examined disordered alcohol and substance use in 351 Irish farmers using the Alcohol Use Disorders Identification Tool (AUDIT) and Drug Use Disorders Identification Tool (DUDIT).
While 28% of farmers did not drink, 40% of those who did drink exceeded the AUDIT threshold for disordered use. Similarly, while 95% of farmers did not use substances, 78% of farmers who did use substances exceeded the DUDIT threshold for disordered use. Age was the most important risk factor for disordered alcohol and substance use and correlated with other main risk factors: lower income, no children, part-time farmer, and full-time off-farm roles. Disordered drinking was highest in farmers engaged in full-time education.
This population of Irish farmers report broadly healthy alcohol and substance use behaviors. Irish farmers may serve as a model group whose strengths can be utilized in interventions within and beyond the Irish farming community. Our results confirm the importance of analyzing demographic factors in farmers' drinking and identify younger farmers as especially at-risk for harmful alcohol and substance use.
Nussbaum's Central Capabilities refer to the elements of a well-lived life, and many adults who experience homelessness are deprived of these capabilities. The study aim was to investigate whether ...service users experience different homeless services as affording or constraining capabilities. We conducted semi-structured interviews with homeless service users (n = 77) in Housing First (HF) and staircase services (SS) in eight European countries. We used thematic analysis to identify three themes: autonomy and dependency, the relational impact of living arrangements, and community interaction and stigma. While SS participants were able to address their bodily integrity and health, their higher-order capabilities were constrained by their homeless situations. HF participants described home as a base from which they could enact a wide range of capabilities indicative of a well-lived life. We conclude that housing-led service models with appropriate supports are key to affording service users' capabilities. Practical and policy implications are discussed.
Accurate information from gravitational wave signals from coalescing binary neutron stars provides essential input to downstream interpretations, including inference of the neutron star population ...and equation of state. However, even adopting the currently most accurate and physically motivated models available for parameter estimation (PE) of BNSs, these models remain subject to waveform modeling uncertainty: differences between these models may introduce biases in recovered source properties. In this work, we describe injection studies investigating these systematic differences between the two best waveform models available for BNS currently, NRHybSur3dq8Tidal and TEOBResumS. We demonstrate that for BNS sources observable by current second-generation detectors, differences for low-amplitude signals are significant for certain sources.
The astrophysical origin of the over 90 compact binary mergers discovered by the LIGO and Virgo gravitational wave observatories is an open question. While the unusual mass and spin of some of the ...discovered objects constrain progenitor scenarios, the observed mergers are consistent with multiple interpretations. A promising approach to solve this question is to consider the observed distributions of binary properties and compare them to expectations from different origin scenarios. Here we describe a new hierarchical population analysis framework to assess the relative contribution of different formation channels simultaneously. For this study we considered binary formation in AGN disks along with phenomenological models, but the same framework can be extended to other models. We find that high-mass and high-mass-ratio binaries appear more likely to have an AGN origin compared to the same origin as lower-mass events. Future observations of high-mass black hole mergers could further disentangle the AGN component from other channels.
Within the next decade, ground based gravitational wave detectors are in principle capable of determining the compact object merger rate per unit volume of the local universe to better than 20% with ...more than 30 detections. Though these measurements can constrain our models of stellar, binary, and cluster evolution in the nearby present-day and ancient universe, we argue that the universe is sufficiently heterogeneous (in age and metallicity distribution at least) and that merger rates predicted by these models can be sufficiently sensitive to those heterogeneities so that a fair comparison of models per unit similar star forming mass necessarily introduces at least an additional 30%--50% systematic error into any constraints on compact binary evolution models. Without adding new electromagnetic constraints on massive binary evolution or relying on more information from each merger (e.g. , binary masses and spins), as few as the {approx_equal}5 merger detections could exhaust the information available in a naive comparison to merger rate predictions. As a concrete example immediately relevant to analysis of initial and enhanced LIGO results, we use a nearby-universe catalog to demonstrate that no one tracer of stellar content can be consistently used to constrain merger rates without introducing a systematic error of order 0(30%) at 90% confidence (depending on the type of binary involved). For example, though binary black holes typically take many Gyr to merge, binary neutron stars often merge rapidly; different tracers of stellar content are required for these two types. More generally, we argue that theoretical binary evolution can depend sufficiently sensitively on star-forming conditions -- even assuming no uncertainty in binary evolution model -- that the distribution of star forming conditions must be incorporated to reduce the systematic error in merger rate predictions below roughly 40%. We emphasize that the degree of sensitivity to star-forming conditions depends on the binary evolution model and on the amount of relevant variation in star-forming conditions. For example, if after further comparison with electromagnetic and gravitational wave observations future population synthesis models suggest all BH-BH binary mergers occur promptly and therefore are associated with well-studied present-day star formation, the associated composition-related systematic uncertainty could be lower than the pessimistic value quoted above. Further, as gravitational wave detectors will make available many properties of each merger -- binary component masses, spins, and even short GRB associations and host galaxies could be available -- many detections can still be exploited to create high-precision constraints on binary compact object formation models.
The advanced interferometer network will herald a new era in observational astronomy. There is a very strong science case to go beyond the advanced detector network and build detectors that operate ...in a frequency range from 1 Hz-10 kHz, with sensitivity a factor ten better in amplitude. Such detectors will be able to probe a range of topics in nuclear physics, astronomy, cosmology and fundamental physics, providing insights into many unsolved problems in these areas.
Multiple myeloma (MM) is a paradigm for a malignant disease that exploits external stimuli of the microenvironment for growth and survival. A thorough understanding of the complex interactions ...between malignant plasma cells and their surrounding requires a detailed analysis of the transcriptional response of myeloma cells to environmental signals. We determined the changes in gene expression induced by interleukin (IL)-6, tumor necrosis factor-α, IL-21 or co-culture with bone marrow stromal cells in myeloma cell lines. Among a limited set of genes that were consistently activated in response to growth factors, a prominent transcriptional target of cytokine-induced signaling in myeloma cells was the gene encoding the serine/threonine kinase serum/glucocorticoid-regulated kinase 1 (SGK1), which is a down-stream effector of PI3-kinase. We could demonstrate a rapid, strong and sustained induction of SGK1 in the cell lines INA-6, ANBL-6, IH-1, OH-2 and MM.1S as well as in primary myeloma cells. Pharmacologic inhibition of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway abolished STAT3 phosphorylation and SGK1 induction. In addition, small hairpin RNA (shRNA)-mediated knock-down of STAT3 reduced basal and induced SGK1 levels. Furthermore, downregulation of SGK1 by shRNAs resulted in decreased proliferation of myeloma cell lines and reduced cell numbers. On the molecular level, this was reflected by the induction of cell cycle inhibitory genes, for example, CDKNA1/p21, whereas positively acting factors such as CDK6 and RBL2/p130 were downregulated. Our results indicate that SGK1 is a highly cytokine-responsive gene in myeloma cells promoting their malignant growth.
To identify genetic events underlying the genesis and progression of multiple myeloma (MM), we conducted a high-resolution analysis of recurrent copy number alterations (CNAs) and expression profiles ...in a collection of MM cell lines and outcome-annotated clinical specimens. Attesting to the molecular heterogeneity of MM, unsupervised classification using nonnegative matrix factorization (NMF) designed for array comparative genomic hybridization (aCGH) analysis uncovered distinct genomic subtypes. Additionally, we defined 87 discrete minimal common regions (MCRs) within recurrent and highly focal CNAs. Further integration with expression data generated a refined list of MM gene candidates residing within these MCRs, thereby providing a genomic framework for dissection of disease pathogenesis, improved clinical management, and initiation of targeted drug discovery for specific MM patients.
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•ISIAQ STC34 has an open database of IEQ guidelines.•Thermal conditions (e.g., T and RH) and indoor pollutants (e.g., CO2, CH2O, PM, NO2, CO, and Rn) can be impacted by energy saving ...measures.•Health based guidelines exist for CH2O, PM2.5, PM10, NO2, CO, and Rn.•Guidelines can help in creating a balance between energy conservation, thermal comfort, and good IAQ.
Buildings are constructed and operated to satisfy human needs and improve quality of life. Good indoor air quality (IAQ) and thermal comfort are prerequisites for human health and well-being. For their provision, buildings often rely on heating, ventilation, and air conditioning (HVAC) systems, which may lead to higher energy consumption. This directly impacts energy efficiency goals and the linked climate change considerations. The balance between energy use, optimum IAQ and thermal comfort calls for scientifically solid and well-established limit values for exposures experienced by building occupants in indoor spaces, including homes, schools, and offices.
The present paper aims to appraise limit values for selected indoor pollutants reported in the scientific literature, and to present how they are handled in international and national guidelines and standards. The pollutants include carbon dioxide (CO2), formaldehyde (CH2O), particulate matter (PM), nitrogen dioxide (NO2), carbon monoxide (CO), and radon (Rn). Furthermore, acknowledging the particularly strong impact on energy use from HVAC, ventilation, indoor temperature (T), and relative humidity (RH) are also included, as they relate to both thermal comfort and the possibilities to avoid moisture related problems, such as mould growth and proliferation of house dust mites.
Examples of national regulations for these parameters are presented, both in relation to human requirements in buildings and considering aspects related to energy saving. The work is based on the Indoor Environmental Quality (IEQ) guidelines database, which spans across countries and institutions, and aids in taking steps in the direction towards a more uniform guidance for values of indoor parameters. The database is coordinated by the Scientific and Technical Committee (STC) 34, as part of ISIAQ, the International Society of Indoor Air Quality and Climate.
Myeloma is a malignant proliferation of monoclonal plasma cells. Although morphologically similar, several subtypes of the disease have been identified at the genetic and molecular level. These ...genetic subtypes are associated with unique clinicopathological features and dissimilar outcome. At the top hierarchical level, myeloma can be divided into hyperdiploid and non-hyperdiploid subtypes. The latter is mainly composed of cases harboring IgH translocations, generally associated with more aggressive clinical features and shorter survival. The three main IgH translocations in myeloma are the t(11;14)(q13;q32), t(4;14)(p16;q32) and t(14;16)(q32;q23). Trisomies and a more indolent form of the disease characterize hyperdiploid myeloma. A number of genetic progression factors have been identified including deletions of chromosomes 13 and 17 and abnormalities of chromosome 1 (1p deletion and 1q amplification). Other key drivers of cell survival and proliferation have also been identified such as nuclear factor- B-activating mutations and other deregulation factors for the cyclin-dependent pathways regulators. Further understanding of the biological subtypes of the disease has come from the application of novel techniques such as gene expression profiling and array-based comparative genomic hybridization. The combination of data arising from these studies and that previously elucidated through other mechanisms allows for most myeloma cases to be classified under one of several genetic subtypes. This paper proposes a framework for the classification of myeloma subtypes and provides recommendations for genetic testing. This group proposes that genetic testing needs to be incorporated into daily clinical practice and also as an essential component of all ongoing and future clinical trials.
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