A search for mixing between active neutrinos and light sterile neutrinos has been performed by looking for muon neutrino disappearance in two detectors at baselines of 1.04 and 735 km, using a ...combined MINOS and MINOS+ exposure of 16.36×10^{20} protons on target. A simultaneous fit to the charged-current muon neutrino and neutral-current neutrino energy spectra in the two detectors yields no evidence for sterile neutrino mixing using a 3+1 model. The most stringent limit to date is set on the mixing parameter sin^{2}θ_{24} for most values of the sterile neutrino mass splitting Δm_{41}^{2}>10^{-4} eV^{2}.
Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, ...respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin^{2}2θ_{μe} are set over 6 orders of magnitude in the sterile mass-squared splitting Δm_{41}^{2}. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Δm_{41}^{2}<0.8 eV^{2} at 95% CL_{s}.
To evaluate mildly abnormal liver function test (LFT) results in general practice among patients who do not have known liver disease.
Prospective cohort study of people with abnormal LFT results ...identified in primary care. Participants were intensively investigated using a common protocol and followed up for 2 years. Substudies investigated the psychological sequelae of abnormal test results, clinicians' reasons for testing, decision options when LFT results were abnormal and early detection of liver fibrosis.
Eleven primary-care practices: eight in Birmingham and three in Lambeth.
Adults with abnormal LFT results who did not have pre-existing or obvious liver disease. Eight analytes were included in the panel of LFTs.
Statistical tests were used to identify the interactions between clinical features, the initial pattern of abnormal LFT results and (1) specific viral, genetic and autoimmune diseases, such as viral hepatitis, haemochromatosis and primary biliary cirrhosis; (2) a range of other serious diseases, such as metastatic cancer and hypothyroidism; (3) 'fatty liver' not associated with the above; and (4) the absence of detectable disease.
Fewer than 5% of people with abnormal LFT results had a specific disease of the liver, and many of these were unlikely to need treatment. The diagnostic potential of the LFT panel is largely subsumed into just two analytes: alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Gamma-glutamyltransferase (GGT) offers a small increase in sensitivity at the margin at the cost of a large loss of specificity. Eighty-four per cent of abnormal LFT results remain abnormal on retesting 1 month later. In many cases, carrying out a definitive or specific test will be more efficient than repeating LFTs, with a view to specific testing only if the test remains abnormal. An ultrasound diagnosis of 'fatty liver' was present in nearly 40% of patients with abnormal LFTs and a small amount of weight loss over 2 years was associated with a reduced incidence of liver fat. There was a J-shaped relationship between alcohol intake and fatty liver in men. An abnormal LFT result causes temporary anxiety, which does not appear to promote sustained behaviour change.
Liver disease is rare among people with abnormal LFT results in primary care. Only two analytes (ALT and ALP) are helpful in identifying the majority of liver disease. GGT adds little information in return for a high false-positive rate but it is sensitive to alcohol intake. LFT results seldom revert from abnormal to normal over a 1-month period, and modelling shows that repeating an abnormal LFT panel, as recommended in the current guidelines, is inefficient. LFTs are often undertaken to meet perceived patient need for a blood test, but as they are neither specific nor indicative of any particular disease they are among the least suitable tests for this purpose. Obesity and raised ALT provide strong evidence for a presumptive diagnosis of 'fatty' liver. Abnormal LFTs and 'fatty' liver provoke only short-term anxiety and neither is associated with sustained weight loss. Even a small amount of weight loss reduces liver fat.
(1) the cases of 'fatty liver' and controls should be followed up in the long term to identify features that predict development of hepatosteatosis and then cirrhosis; (2) the acceptability of replacing the traditional six- to eight-analyte LFT panel with a drop down menu including the ALT/ALP combination should be evaluated.
The National Institute for Health Research Health Technology Assessment programme.
To evaluate 5-year outcomes after lower limb realignment and test the hypothesis that surgery-induced changes in selected biomechanical risk factors for medial knee osteoarthritis (OA) are associated ...with clinically important improvements.
We prospectively evaluated patient-reported outcomes, full-limb standing radiographs and gait biomechanics before, 6 months (surgery-induced change) and 5 years after medial opening wedge high tibial osteotomy (HTO) in 170 patients (46.4 ± 8.9 years, 135 males) with knee OA and varus alignment. Logistic regression tested the associations of 6-month changes in mechanical axis angle and knee adduction moment with achieving an increase of ≥10 points in the Knee injury and Osteoarthritis Outcome Score (KOOS)4 at 5 years, with and without adjusting for covariates. Gait data were also compared to existing data from healthy controls.
Mean 5-year changes (95% confidence interval (CI)) were: KOOS4: +14.2 (10.8, 17.6); mechanical axis angle: +8.21° (7.58, 8.83); knee adduction moment: −1.49 %BW*Ht (−1.35, −1.63). The postoperative knee adduction moments were typically lower than values for healthy controls. When divided into quartiles, although all strata improved significantly, patients with reductions in knee adduction moment of 1.14–1.74 %BW*Ht (neither largest nor smallest changes) had highest 5-year KOOS4 scores. The 6-month change in knee adduction moment (odds ratios (OR) = 0.38; 95% CI: 0.22, 0.67), preoperative KOOS4 (OR = 0.96; 95% CI: 0.94, 0.99) and preoperative medial tibiofemoral narrowing grade (OR = 0.62; 95% CI: 0.37, 1.00) were negatively associated with having a 5-year clinically important improvement (C-statistic = 0.70).
Substantial improvements in biomechanical risk factors and patient-reported outcomes are observed 5 years after medial opening wedge HTO. The surgery-induced change in load distribution during walking is significantly associated with long-term clinically important improvement.
Severe maternal morbidity in Scotland Masterson, J. A.; Adamestam, I.; Beatty, M. ...
Anaesthesia,
September 2022, 2022-09-00, 20220901, Letnik:
77, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Summary
Using a cohort study design, we analysed 17 diagnoses and 9 interventions (including critical care admission) as a composite measure of severe maternal morbidity for pregnancies recorded over ...14 years in Scotland. There were 762,918 pregnancies, of which 7947 (10 in 1000 pregnancies) recorded 9345 severe maternal morbidity events, 2802 episodes of puerperal sepsis being the most common (30%). Severe maternal morbidity incidence increased from 9 in 1000 pregnancies in 2012 to 17 in 1000 pregnancies in 2018, due in part to puerperal sepsis recording. The odds ratio (95%CI) for severe maternal morbidity was higher for: older women, for instance 1.22 (1.13–1.33) for women aged 35–39 years and 1.44 (1.27–1.63) for women aged > 40 years compared with those aged 25–29 years; obese women, for instance 1.13 (1.06–1.21) for BMI 30–40 kg.m‐2 and 1.32 (1.15–1.51) for BMI > 40 kg.m‐2 compared with BMI 18.5–24.9 kg.m‐2; multiple pregnancy, 2.39 (2.09–2.74); and previous caesarean delivery, 1.52 (1.40–1.65). The median (IQR range) hospital stay was 3 (2–5 1–8) days with severe maternal morbidity and 2 (1–3 1–5) days without. Forty‐one women died during pregnancy or up to 42 days after delivery, representing mortality rates per 100,000 pregnancies of about 365 with severe maternal morbidity and 1.6 without. There were 1449 women admitted to critical care, 807 (58%) for mechanical ventilation or support of at least two organs. We recorded an incidence of severe maternal morbidity higher than previously published, possibly because sepsis was coded inaccurately in our databases. Further research may determine the value of this composite measure of severe maternal morbidity.
We report new constraints on the size of large extra dimensions from data collected by the MINOS experiment between 2005 and 2012. Our analysis employs a model in which sterile neutrinos arise as ...Kaluza-Klein states in large extra dimensions and thus modify the neutrino oscillation probabilities due to mixing between active and sterile neutrino states. Using Fermilab’s Neutrinos at the Main Injector beam exposure of 10.56×1020 protons on target, we combine muon neutrino charged current and neutral current data sets from the Near and Far Detectors and observe no evidence for deviations from standard three-flavor neutrino oscillations. The ratios of reconstructed energy spectra in the two detectors constrain the size of large extra dimensions to be smaller than 0.45 μm at 90% C.L. in the limit of a vanishing lightest active neutrino mass. Stronger limits are obtained for nonvanishing masses.
Purpose: To evaluate short-term outcomes of combined ab intemo canaloplasty and trabeculotomy in pseudophakic eyes with openangle glaucoma. Patients and Methods: Series included all pseudophakic eyes ...with open-angle glaucoma treated with up to 360degrees ab interno canaloplasty and up to 360degrees ab interno trabeculotomy using a purpose-engineered device (OMNI, Sight Sciences Inc). Data collected prior to surgery and out to 6-months postoperative. Surgical success defined as a 20% reduction in intraocular pressure (IOP) without increase in glaucoma medication, or discontinuation of at least one glaucoma medication without increase in IOP. Other primary endpoints included mean IOP and number of glaucoma medications. Results: The study included 67 eyes of 52 patients with a mean age of 76.5 + or - 8.9 years. Preoperative mean IOP was 22.1 + or - 8.0 mmHg on 2.3 + or - 1.4 glaucoma medications. Pressure lowering effects were sustained out to 6 months postoperative with a mean IOP of 15.2 + or - 4.9 mmHg (p < 0.001) and mean medication reduction of 0.7 + or - 1.4 (p < 0.001). Surgical success rate was 69.8% (30 eyes) and correlated with preoperative IOP. Two patients required a secondary surgical intervention. Conclusion: Combined ab interno canaloplasty and trabeculotomy as a standalone procedure is an effective means of reducing IOP and medication burden in pseudophakic eyes with open-angle glaucoma. Keywords: glaucoma, pseudophakia, MIGS, Schlemm canal
Efforts are being directed to systematically analyze the non-coding regions of the genome for cancer-driving mutations
. cis-regulatory elements (CREs) represent a highly enriched subset of the ...non-coding regions of the genome in which to search for such mutations. Here we use high-throughput chromosome conformation capture techniques (Hi-C) for 19,023 promoter fragments to catalog the regulatory landscape of colorectal cancer in cell lines, mapping CREs and integrating these with whole-genome sequence and expression data from The Cancer Genome Atlas
. We identify a recurrently mutated CRE interacting with the ETV1 promoter affecting gene expression. ETV1 expression influences cell viability and is associated with patient survival. We further refine our understanding of the regulatory effects of copy-number variations, showing that RASL11A is targeted by a previously identified enhancer amplification
. This study reveals new insights into the complex genetic alterations driving tumor development, providing a paradigm for employing chromosome conformation capture to decipher non-coding CREs relevant to cancer biology.
Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have ...been applied to an enlarged data sample from an exposure of 7.25×10(20) protons on target. A fit to neutrino oscillations yields values of |Δm(2)|=(2.32(-0.08)(+0.12))×10(-3) eV(2) for the atmospheric mass splitting and sin(2)(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively.
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