Problems and needs for improving primary care of osteoarthritis patients: the views of patients, general practitioners and practice nurses

BACKGROUND: Osteoarthritis (OA) is highly prevalent and has substantial impact on quality of life as well as on healthcare costs. The general practitioner (GP) often is the first care provider for patients with this chronic disease. The aim of this study was to identify health care needs of patients with OA and to reveal possible obstacles for improvements in primary care management of OA patients. METHODS: We performed semi-structured interviews with a stratified sample of 20 patients, 20 GPs and 20 practice nurses. RESULTS: Diagnosing OA posed no major problem, but during the course of OA, GPs found it difficult to distinguish between complaints resulting from the affection of the joints and complaints related to a concomitant depression. Patients felt to be well informed about the degenerative nature of the disease and possible side effects of medications, but they lacked information on individual consequences of the disease. Therefore, the most important concerns of many patients were pain and fear of disability which they felt to be addressed by GPs only marginally. Regarding pain treatment, physicians and patients had an ambivalent attitude towards NSAIDs and opiates. Therefore, pain treatment was not performed according to prevailing guidelines. GPs felt frustrated about the impact of counselling regarding life style changes but on the other hand admitted to have no systematic approach to it. Patients stated to be aware of the impact of life style on OA but lacked detailed information e.g. on how to exercise. Several suggestions were made concerning improvement. CONCLUSION: GPs should focus more on disability and pain and on giving information about treatment since these topics are inadequately addressed. Advanced approaches are needed to increase GPs impact on patients' life style. Being aware of the problem of labelling patients as chronically ill, a more proactive, patient-centred care is needed

Enhanced Inflammatory Potential of CD4(+) T-Cells That Lack Proteasome Immunosubunit Expression, in a T-Cell Transfer-Based Colitis Model

Proteasomes play a fundamental role in intracellular protein degradation and therewith regulate a variety of cellular processes. Exposure of cells to (pro)inflammatory cytokines upregulates the expression of three inducible catalytic proteasome subunits, the immunosubunits, which incorporate into newly assembled proteasome complexes and alter the catalytic activity of the cellular proteasome population. Single gene-deficient mice lacking one of the three immunosubunits are resistant to dextran sulfate sodium (DSS)-induced colitis development and, likewise, inhibition of one single immunosubunit protects mice against the development of DSS-induced colitis. The observed diminished disease susceptibility has been attributed to altered cytokine production and CD4+ T-cell differentiation in the absence of immunosubunits. To further test whether the catalytic activity conferred by immunosubunits plays an essential role in CD4+ T-cell function and to distinguish between the role of immunosubunits in effector T-cells versus inflamed tissue, we used a T-cell transfer-induced colitis model. Naïve wt or immunosubunit-deficient CD4+ T-cells were adoptively transferred into RAG1-/- and immunosubunit-deficient RAG1-/- mice and colitis development was determined six weeks later. While immunosubunit expression in recipient mice had no effect on colitis development, transferred immunosubunit-deficient T- cells were more potent in inducing colitis and produced more proinflammatory IL17 than wt T-cells. Taken together, our data show that modifications in proteasome-mediated proteolysis in T-cells, conferred by lack of immunosubunit incorporation, do not attenuate but enhance CD4+ T-cell-induced inflammation

Population genomics of marine zooplankton

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Bucklin, Ann et al. "Population Genomics of Marine Zooplankton." Population Genomics: Marine Organisms. Ed. Om P. Rajora and Marjorie Oleksiak. Springer, 2018. doi:10.1007/13836_2017_9.The exceptionally large population size and cosmopolitan biogeographic distribution that distinguish many – but not all – marine zooplankton species generate similarly exceptional patterns of population genetic and genomic diversity and structure. The phylogenetic diversity of zooplankton has slowed the application of population genomic approaches, due to lack of genomic resources for closelyrelated species and diversity of genomic architecture, including highly-replicated genomes of many crustaceans. Use of numerous genomic markers, especially single nucleotide polymorphisms (SNPs), is transforming our ability to analyze population genetics and connectivity of marine zooplankton, and providing new understanding and different answers than earlier analyses, which typically used mitochondrial DNA and microsatellite markers. Population genomic approaches have confirmed that, despite high dispersal potential, many zooplankton species exhibit genetic structuring among geographic populations, especially at large ocean-basin scales, and have revealed patterns and pathways of population connectivity that do not always track ocean circulation. Genomic and transcriptomic resources are critically needed to allow further examination of micro-evolution and local adaptation, including identification of genes that show evidence of selection. These new tools will also enable further examination of the significance of small-scale genetic heterogeneity of marine zooplankton, to discriminate genetic “noise” in large and patchy populations from local adaptation to environmental conditions and change.Support was provided by the US National Science Foundation to AB and RJO (PLR-1044982) and to RJO (MCB-1613856); support to IS and MC was provided by Nord University (Norway)

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO’s second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h95%0=3.47×10−25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering