Heat Flow Measurements at the Danube Deep-Sea Fan, Western Black Sea

Seafloor heat flow measurements are utilized to determine the geothermal regime of the Danube deep-sea fan in the western Black Sea and are presented in the larger context of regional gas hydrate occurrences. Heat flow data were collected across paleo-channels in water depths of 550–1460 m. Heat flow across levees ranges from 25 to 30 mW m−2 but is up to 65 mW m−2 on channel floors. Gravity coring reveals sediment layers typical of the western Black Sea, consisting of three late Pleistocene to Holocene units, notably red clay within the lowermost unit cored. Heat flow derived from the bottom-simulating reflector (BSR), assumed to represent the base of the gas hydrate stability zone (GHSZ), deviates from seafloor measurements. These discrepancies are linked either to fast sedimentation or slumping and associated variations in sediment physical properties. Topographic effects account of up to 50% of heat flow deviations from average values. Combined with climate-induced variations in seafloor temperature and sea-level since the last glacial maximum large uncertainties in the prediction of the base of the GHSZ remain. A regional representative heat flow value is ~30 mW m−2 for the study region but deviations from this value may be up to 100%

Realism and Experiments: Investigating Virtual Reality Experiments

Experimental research is a fundamental component of scientific inquiry, but the realism of experimental settings may be limited due to a trade-off between internal and external validity. Virtual Reality technology offers a potential solution to this problem by creating highly controlled, yet realistic experimental settings. In this study, we investigate the potential of VR to increase perceived realism in experimental research by identifying and examining the effects of VR experiments on participants\u27 perceived realism. In our experiment, we compare the level of perceived realism between artificial scenarios presented as text vignettes and in VR. Our findings indicate that VR experiments elicite a significantly higher level of perceived realism compared to text-based experiments. Additionally, we use partial least squares structural equation modeling to investigate the identified concepts. We recommend that researchers consider using VR technology to enhance the realism of experimental settings and improve the validity of their findings

PAQ: 65 Million Probably-Asked Questions and What You Can Do With Them

Open-domain Question Answering models which directly leverage question-answer (QA) pairs, such as closed-book QA (CBQA) models and QA-pair retrievers, show promise in terms of speed and memory compared to conventional models which retrieve and read from text corpora. QA-pair retrievers also offer interpretable answers, a high degree of control, and are trivial to update at test time with new knowledge. However, these models lack the accuracy of retrieve-and-read systems, as substantially less knowledge is covered by the available QA-pairs relative to text corpora like Wikipedia. To facilitate improved QA-pair models, we introduce Probably Asked Questions (PAQ), a very large resource of 65M automatically-generated QA-pairs. We introduce a new QA-pair retriever, RePAQ, to complement PAQ. We find that PAQ preempts and caches test questions, enabling RePAQ to match the accuracy of recent retrieve-and-read models, whilst being significantly faster. Using PAQ, we train CBQA models which outperform comparable baselines by 5%, but trail RePAQ by over 15%, indicating the effectiveness of explicit retrieval. RePAQ can be configured for size (under 500MB) or speed (over 1K questions per second) whilst retaining high accuracy. Lastly, we demonstrate RePAQ's strength at selective QA, abstaining from answering when it is likely to be incorrect. This enables RePAQ to ``back-off" to a more expensive state-of-the-art model, leading to a combined system which is both more accurate and 2x faster than the state-of-the-art model alone

Validity and responsiveness of the EQ-5D in assessing and valuing health status in patients with anxiety disorders

<p>Abstract</p> <p>Background</p> <p>The EQ-5D is a generic questionnaire which generates a health profile as well as index scores for health-related quality of life that may be used in cost-utility analysis.</p> <p>Aims of the study</p> <p>To examine validity and responsiveness of the EQ-5D in patients with anxiety disorders.</p> <p>Methods</p> <p>389 patients with anxiety disorders completed the EQ-5D at baseline and 6-month follow-up. Subjective measures of quality of life (WHOQOL-BREF) and psychopathology (BAI, BDI-II, BSQ, ACQ, MI) were used for comparison. Validity was analyzed by assessing associations between EQ-5D scores and related other scores. Responsiveness was analyzed by calculating effect sizes of differences in scores between baseline and follow-up for 3 groups indicating more, constant or less anxiety. Meaningful difference scores for shifting to less or more anxiety were derived by means of regression analysis.</p> <p>Results</p> <p>88.4% of respondents reported problems in at least one of the EQ-5D dimension at baseline; the mean EQ VAS score was 63.8. The EQ-5D dimension most consistently associated with the measures used for comparison was 'anxiety/depression'. EQ VAS and EQ-5D index scores were highly correlated (|r|>0.5) with scores of the WHOQOL-BREF dimensions 'physical', 'mental' and 'overall' as well as BAI and BDI-II. The EQ-5D index tended to be the most responsive score. Standardized meaningful difference scores were not significantly different between EQ VAS, EQ-5D index and measures used for comparison.</p> <p>Conclusions</p> <p>The EQ-5D seems to be reasonably valid and moderately responsive in patients with anxiety disorders. The EQ-5D index may be suitable for calculating QALYs in economic evaluation of health care interventions for patients with anxiety disorders.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN15716049</p

Retrieval-Augmented Generation for Knowledge-Intensive NLP Tasks

Large pre-trained language models have been shown to store factual knowledge in their parameters, and achieve state-of-the-art results when fine-tuned on downstream NLP tasks. However, their ability to access and precisely manipulate knowledge is still limited, and hence on knowledge-intensive tasks, their performance lags behind task-specific architectures. Additionally, providing provenance for their decisions and updating their world knowledge remain open research problems. Pre-trained models with a differentiable access mechanism to explicit non-parametric memory can overcome this issue, but have so far been only investigated for extractive downstream tasks. We explore a general-purpose fine-tuning recipe for retrieval-augmented generation (RAG) -- models which combine pre-trained parametric and non-parametric memory for language generation. We introduce RAG models where the parametric memory is a pre-trained seq2seq model and the non-parametric memory is a dense vector index of Wikipedia, accessed with a pre-trained neural retriever. We compare two RAG formulations, one which conditions on the same retrieved passages across the whole generated sequence, the other can use different passages per token. We fine-tune and evaluate our models on a wide range of knowledge-intensive NLP tasks and set the state-of-the-art on three open domain QA tasks, outperforming parametric seq2seq models and task-specific retrieve-and-extract architectures. For language generation tasks, we find that RAG models generate more specific, diverse and factual language than a state-of-the-art parametric-only seq2seq baseline.Comment: Accepted at NeurIPS 202

The selection and definition of indicators in public health monitoring for the 65+ age group in Germany

Selecting relevant indicators is an important step in the development of public health monitoring for older people. Indicators can be used to combine information comprehensively from various data sources and enable recurring, comparable findings to be made about the health of older people. Indicators were systematically compiled from existing international monitoring systems. An indicator set on health in old age was developed using a multistage, structured consensus-based process together with an interdisciplinary panel of experts. The resulting 18 indicators were assigned to three health areas: (1) environmental factors, (2) activities and participation, and (3) personal factors. Data sources that can be used for the indicators are the health surveys within the framework of the Robert Koch Institute’s (RKI) health monitoring system, as well as surveys from other research institutes and official statistics. In the future, the indicator set is to be developed further and integrated into an overall approach that is geared towards health reporting and the monitoring of chronic diseases in all phases of life

Dose-escalation study of a second-generation non-ansamycin HSP90 inhibitor, onalespib (AT13387), in combination with imatinib in patients with metastatic gastrointestinal stromal tumour

AbstractBackgroundGastrointestinal stromal tumours (GIST) treated with the tyrosine kinase inhibitor (TKI) imatinib can become resistant when additional mutations in the receptor tyrosine kinases KIT or PDGFRA block imatinib activity. Mutated KIT requires the molecular chaperone heat-shock protein 90 (HSP90) to maintain stability and activity. Onalespib (AT13387) is a potent non-ansamycin HSP90 inhibitor. We hypothesised that the combination of onalespib and imatinib may be safe and effective in managing TKI-resistant GIST.Patients and methodsIn this dose-escalation study, we evaluated the safety and efficacy of combination once-weekly intravenous onalespib for 3 weeks and daily oral imatinib in 28-d cycles. Twenty-six patients with TKI-resistant GIST were enrolled into four sequential dose cohorts of onalespib (dose range, 150–220 mg/m2) and imatinib 400 mg. The relationship between tumour mutational status (KIT/PDGFRA) and efficacy of treatment was explored.ResultsCommon onalespib-related adverse events were diarrhoea (58%), nausea (50%), injection site events (46%), vomiting (39%), fatigue (27%), and muscle spasms (23%). Overall, 81% of patients reported more than one onalespib-related gastrointestinal disorder. Nine patients (35%) had a best response of stable disease, including two patients who had KIT mutations known to be associated with resistance to imatinib and sunitinib. Disease control at 4 months was achieved in five patients (19%), and median progression-free survival was 112 d (95% confidence interval 43–165). One patient with PDGFRA-mutant GIST had a partial response for more than 376 d.ConclusionThe combination of onalespib plus imatinib was well tolerated but exhibited limited antitumour activity as dosed in this TKI-resistant GIST patient population.Trial registration ID: clinicaltrials.gov: NCT0129420

Growing old at home – A randomized controlled trial to investigate the effectiveness and cost-effectiveness of preventive home visits to reduce nursing home admissions: study protocol [NCT00644826]

<p>Abstract</p> <p>Background</p> <p>Regarding demographic changes in Germany it can be assumed that the number of elderly and the resulting need for long term care is increasing in the near future. It is not only an individual's interest but also of public concern to avoid a nursing home admission. Current evidence indicates that preventive home visits can be an effective way to reduce the admission rate in this way making it possible for elderly people to stay longer at home than without home visits. As the effectiveness and cost-effectiveness of preventive home visits strongly depends on existing services in the social and health system existing international results cannot be merely transferred to Germany. Therefore it is necessary to investigate the effectiveness and cost-effectiveness of such an intervention in Germany by a randomized controlled trial.</p> <p>Methods</p> <p>The trial is designed as a prospective multi-center randomized controlled trial in the cities of Halle and Leipzig. The trial includes an intervention and a control group. The control group receives usual care. The intervention group receives three additional home visits by non-physician health professionals (1) geriatric assessment, (2) consultation, (3) booster session.</p> <p>The nursing home admission rate after 18 months will be defined as the primary outcome. An absolute risk reduction from a 20% in the control-group to a 7% admission rate in the intervention group including an assumed drop out rate of 30% resulted in a required sample size of N = 320 (n = 160 vs. n = 160).</p> <p>Parallel to the clinical outcome measurement the intervention will be evaluated economically. The economic evaluation will be performed from a society perspective.</p> <p>Discussion</p> <p>To the authors' knowledge for the first time a trial will investigate the effectiveness and cost-effectiveness of preventive home visits for people aged 80 and over in Germany using the design of a randomized controlled trial. Thus, the trial will contribute to the existing evidence on preventive home visits especially in Germany.</p

Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow

At present, it is not clear how memory B lymphocytes are maintained over time, and whether only as circulating cells or also residing in particular tissues. Here we describe distinct populations of isotype-switched memory B lymphocytes (Bsm) of murine spleen and bone marrow, identified according to individual transcriptional signature and B cell receptor repertoire. A population of marginal zone-like cells is located exclusively in the spleen, while a population of quiescent Bsm is found only in the bone marrow. Three further resident populations, present in spleen and bone marrow, represent transitional and follicular B cells and B1 cells, respectively. A population representing 10-20% of spleen and bone marrow memory B cells is the only one qualifying as circulating. In the bone marrow, all cells individually dock onto VCAM1+ stromal cells and, reminiscent of resident memory T and plasma cells, are void of activation, proliferation and mobility