Spaceborne VHSIC multiprocessor system for AI applications

A multiprocessor system, under design for space-station applications, makes use of the latest generation symbolic processor and packaging technology. The result will be a compact, space-qualified system two to three orders of magnitude more powerful than present-day symbolic processing systems

Principles for research on ethnicity and health: the Leeds consensus statement

Background: There is substantial evidence that health and health-care experiences vary along ethnic lines and the need to understand and tackle ethnic health inequalities has repeatedly been highlighted. Research into ethnicity and health raises ethical, theoretical and methodological issues and, as the volume of research in this area grows, so too do concerns regarding its scientific rigour and reporting, and its contribution to reducing inequalities. Guidance may be helpful in encouraging researchers to adopt standard practices in the design, conduct and reporting of research. However, past efforts at introducing such guidance have had limited impact on research practice, and the diversity of disciplinary perspectives on the key challenges and solutions may undermine attempts to derive and promote guiding principles. Methods: A consensus building Delphi exercise—the first of its kind in this area of research practice—was undertaken with leading academics, practitioners and policymakers from a broad range of disciplinary backgrounds to assess whether consensus on key principles could be achieved. Results: Ten key principles for conducting research on ethnicity and health emerged, covering: the aims of research in this field; how such research should be framed and focused; key design-related considerations; and the direction of future research. Despite some areas of dispute, participants were united by a common concern that the generation and application of research evidence should contribute to better health-care experiences and health outcomes for minority ethnic people. Conclusion: The principles provide a strong foundation to guide future ethnicity-related research and build a broader international consensus

Open‐label, clinical trial extension:Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis

SummaryBackgroundSeladelpar is a potent and selective peroxisome proliferator‐activated receptor‐δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti‐cholestatic, anti‐inflammatory and anti‐pruritic effects.AimsTo evaluate the long‐term safety and efficacy of seladelpar in patients with PBC.MethodsIn an open‐label, international, long‐term extension study, patients with PBC completing seladelpar lead‐in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non‐alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years.ResultsThere were no serious treatment‐related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] &lt;1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2.ConclusionsSeladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year. Clinicaltrials.gov: NCT03301506; Clinicaltrialsregister.eu: 2017‐003910‐16.</jats:sec

The impact on hospital resource utilisation of treatment of hepatic encephalopathy with rifaximin-α

BACKGROUND & AIMS: Rifaximin-α reduces the risk of recurrence of overt hepatic encephalopathy. However, there remain concerns regarding the financial cost of the drug. We aimed to study the impact of treatment with rifaximin-α on healthcare resource utilisation using data from seven UK liver treatment centres. METHODS: All seven centres agreed a standardised data set and data characterising clinical, demographic and emergency hospital admissions were collected retrospectively for the time periods 3, 6 and 12 months before and following initiation of rifaximin-α. Admission rates and hospital length of stay before and during therapy were compared. Costs of admissions and drug acquisition were estimated using published sources. Multivariate analyses were carried out to assess the relative impact of various factors on hospital length of stay. RESULTS: Data were available from 326 patients. Following the commencement of rifaximin, the total hospital length of stay reduced by an estimated 31-53%, equating to a reduction in inpatient costs of between £4858 and £6607 per year. Taking into account drug costs of £3379 for 1-year treatment with rifaximin-α, there was an estimated annual mean saving of £1480-£3228 per patient. CONCLUSIONS: Initiation of treatment with rifaximin-α was associated with a marked reduction in the number of hospital admissions and hospital length of stay. These data suggest that treatment of patients with rifaximin-α for hepatic encephalopathy was generally cost saving

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study

Background and Aims: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). Approach and Results: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) &lt; 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) (p &lt; 0.0001). ALP normalization occurred in 5.4% (p=0.08) and 27.3% (p &lt; 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: −3.14 (p=0.02); placebo: −1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% (p=0.0008); 10 mg: 16.7% (p=0.03); placebo: 4%]. There were no serious treatment-related adverse events. Conclusions: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated

Campylobacter Infection as a Trigger for Guillain-Barré Syndrome in Egypt

BACKGROUND: Most studies of Campylobacter infection triggering Guillain-Barré Syndrome (GBS) are conducted in western nations were Campylobacter infection and immunity is relatively rare. In this study, we explored Campylobacter infections, Campylobacter serotypes, autoantibodies to gangliosides, and GBS in Egypt, a country where Campylobacter exposure is common. METHODS: GBS cases (n = 133) were compared to age- and hospital-matched patient controls (n = 374). A nerve conduction study was performed on cases and a clinical history, serum sample, and stool specimen obtained for all subjects. RESULTS: Most (63.3%) cases were demyelinating type; median age four years. Cases were more likely than controls to have diarrhea (29.5% vs. 22.5%, Adjusted Odds Ratio (ORa) = 1.69, P = 0.03), to have higher geometric mean IgM anti-Campylobacter antibody titers (8.18 vs. 7.25 P<0.001), and to produce antiganglioside antibodies (e.g., anti-Gd1a, 35.3 vs. 11.5, ORa = 4.39, P<0.0001). Of 26 Penner:Lior Campylobacter serotypes isolated, only one (41:27, C. jejuni, P = 0.02) was associated with GBS. CONCLUSIONS: Unlike results from western nations, data suggested that GBS cases were primarily in the young and cases and many controls had a history of infection to a variety of Campylobacter serotypes. Still, the higher rates of diarrhea and greater antibody production against Campylobacter and gangliosides in GBS patients were consistent with findings from western countries

Ten facts about land systems for sustainability

Land use is central to addressing sustainability issues, including biodiversity conservation, climate change, food security, poverty alleviation, and sustainable energy. In this paper, we synthesize knowledge accumulated in land system science, the integrated study of terrestrial social-ecological systems, into 10 hard truths that have strong, general, empirical support. These facts help to explain the challenges of achieving sustainability in land use and thus also point toward solutions. The 10 facts are as follows: 1) Meanings and values of land are socially constructed and contested; 2) land systems exhibit complex behaviors with abrupt, hard-to-predict changes; 3) irreversible changes and path dependence are common features of land systems; 4) some land uses have a small footprint but very large impacts; 5) drivers and impacts of land-use change are globally interconnected and spill over to distant locations; 6) humanity lives on a used planet where all land provides benefits to societies; 7) land-use change usually entails trade-offs between different benefits—"win–wins" are thus rare; 8) land tenure and land-use claims are often unclear, overlapping, and contested; 9) the benefits and burdens from land are unequally distributed; and 10) land users have multiple, sometimes conflicting, ideas of what social and environmental justice entails. The facts have implications for governance, but do not provide fixed answers. Instead they constitute a set of core principles which can guide scientists, policy makers, and practitioners toward meeting sustainability challenges in land use

The 'lived experience' of palliative care patients in one acute hospital setting - a qualitative study

Background There is limited understanding of the ‘lived experience’ of palliative care patient within the acute care setting. Failing to engage with and understand the views of patients and those close to them, has fundamental consequences for future health delivery. Understanding ‘patient experience’ can enable care providers to ensure services are responsive and adaptive to individual patient need. Methods The aim of this study was to explore the ‘lived experience’ of a group of patients with palliative care needs who had recently been in-patients in one acute hospital trust in the north-west of England. Qualitative research using narrative interviews was undertaken, and data was analysed using thematic analysis. A sample of 20 consecutive patients complying with the inclusion/exclusion criteria were recruited and interviewed. Results Patient Sample: Of the 20 patients recruited, there was a fairly equal gender split; all had a cancer diagnosis and the majority were white British, with an age range of 43–87 years. Findings from Interviews: Overall inpatient experience was viewed positively. Individual narratives illustrated compassionate and responsive care, with the patient at the centre. Acts of compassion appeared to be expressed through the ‘little things’ staff could do for patients, i.e., time to talk, time to care, humanity and comfort measures. AHSPCT involvement resulted in perceived improvements in pain control and holistic wellbeing. However, challenges were evident, particularly regarding over-stretched staff and resources, and modes of communication, which seemed to impact on patient experience. Conclusions Listening to patients’ experiences of care across the organisation provided a unique opportunity to impact upon delivery of care. Further research should focus on exploring issues such as: why some patients within the same organisation have a positive experience of care, while others may not; how do staff attitudes and behaviours impact on the experience of care; transitions of care from hospital to home, and the role of social networks