Mechanisms of quadriceps muscle weakness in knee joint osteoarthritis: the effects of prolonged vibration on torque and muscle activation in osteoarthritic and healthy control subjects

Introduction: A consequence of knee joint osteoarthritis (OA) is an inability to fully activate the quadriceps muscles, a problem termed arthrogenic muscle inhibition (AMI). AMI leads to marked quadriceps weakness that impairs physical function and may hasten disease progression. The purpose of the present study was to determine whether g-loop dysfunction contributes to AMI in people with knee joint OA. Methods: Fifteen subjects with knee joint OA and 15 controls with no history of knee joint pathology participated in this study. Quadriceps and hamstrings peak isometric torque (Nm) and electromyography (EMG) amplitude were collected before and after 20 minutes of 50 Hz vibration applied to the infrapatellar tendon. Between-group differences in pre-vibration torque were analysed using a one-way analysis of covariance, with age, gender and body mass (kg) as the covariates. If the g-loop is intact, vibration should decrease torque and EMG levels in the target muscle; if dysfunctional, then torque and EMG levels should not change following vibration. One-sample t tests were thus undertaken to analyse whether percentage changes in torque and EMG differed from zero after vibration in each group. In addition, analyses of covariance were utilised to analyse between-group differences in the percentage changes in torque and EMG following vibration. Results: Pre-vibration quadriceps torque was significantly lower in the OA group compared with the control group (P = 0.005). Following tendon vibration, quadriceps torque (P < 0.001) and EMG amplitude (P ≤0.001) decreased significantly in the control group but did not change in the OA group (all P > 0.299). Hamstrings torque and EMG amplitude were unchanged in both groups (all P > 0.204). The vibration-induced changes in quadriceps torque and EMG were significantly different between the OA and control groups (all P < 0.011). No between-group differences were observed for the change in hamstrings torque or EMG (all P > 0.554). Conclusions: g-loop dysfunction may contribute to AMI in individuals with knee joint OA, partially explaining the marked quadriceps weakness and atrophy that is often observed in this population

Galaxy redshift surveys selected by neutral hydrogen using FAST

We discuss the possibility of performing a substantial spectroscopic galaxy redshift survey selected via the 21cm emission from neutral hydrogen using the Five-hundred metre Aperture Spherical Telescope (FAST) to be built in China. We consider issues related to the estimation of the source counts and optimizations of the survey, and discuss the constraints on cosmological models that such a survey could provide. We find that a survey taking around two years could detect ~10^7 galaxies with an average redshift of ~0.15 making the survey complementary to those already carried out at optical wavelengths. These conservative estimates have used the z=0 HI mass function and have ignored the possibility of evolution. The results could be used to constrain Gamma = (Omega_m h) to 5 per cent and the spectral index, n_s, to 7 per cent independent of cosmic microwave background data. If we also use simulated power spectra from the Planck satellite, we can constrain w to be within 5 per cent of -1.Comment: 13 pages, 15 figures, Accepted by MNRAS, minor correction

SN 2006bp: Probing the Shock Breakout of a Type II-P Supernova

HET optical spectroscopy and unfiltered ROTSE-III photometry spanning the first 11 months since explosion of the Type II-P SN 2006bp are presented. Flux limits from the days before discovery combined with the initial rapid brightening suggest the supernova was first detected just hours after shock breakout. Optical spectra obtained about 2 days after breakout exhibit narrow emission lines corresponding to HeII 4200, HeII 4686, and CIV 5805 in the rest frame, and these features persist in a second observation obtained 5 hours later; however, these emission lines are not detected the following night nor in subsequent observations. We suggest that these lines emanate from material close to the explosion site, possibly in the outer layers of the progenitor that have been ionized by the high energy photons released at shock breakout. A P-Cygni profile is observed around 4450 A in the +2 and +3 day spectra. Previous studies have attributed this feature to high velocity H-beta, but we discuss the possibility that this profile is instead due to HeII 4687. Further HET observations (14 nights in total) covering the spectral evolution across the photometric plateau up to 73 days after breakout and during the nebular phase around day +340 are presented, and expansion velocities are derived for key features. The measured decay slope for the unfiltered light curve is 0.0073 +/- 0.0004 mag/day between days +121 and +335, which is significantly slower than the decay of rate 56Co. We combine our HET measurements with published X-ray, UV, and optical data to obtain a quasi-bolometric light curve through day +60. We see a slow cooling over the first 25 days, but no sign of an early sharp peak; any such feature from the shock breakout must have lasted less than ~1 day.[ABRIDGED]Comment: ApJ accepted, 43 page

Longer-term mortality following SARS-CoV-2 infection in people with severe mental illness: retrospective case-matched study.

Persisting symptoms and dysfunction after SARS-CoV-2 infection have frequently been observed. However, information on the aftermath of COVID-19 is inadequate. We followed up people with severe mental illness (SMI) infected with SARS-CoV-2, and evaluated their longer-term mortality, using data from Cambridgeshire and Peterborough NHS Foundation Trust, UK. We examined the time course and duration of mortality risk from the point of diagnosis. After SARS-CoV-2 infection, people with SMI had a substantially higher risk of death (hazard ratio (HR) = 5.16, 95% confidence interval (CI) 1.56-17.03; P = 0.007) during the first 28 days and during the following 28-60 days (HR = 2.96, 95% CI 1.21-7.26; P = 0.018) than those without infection, but after 60 days the additional risk of death was no longer significant (HR = 2.33, 95% CI 0.83-6.53; P = 0.107)

Extraordinary Late-Time Infrared Emission of Type IIn Supernovae

Near-Infrared (NIR) observations are presented for five Type IIn supernovae (SN 1995N, SN 1997ab, SN 1998S, SN 1999Z, and SN 1999el) that exhibit strong infrared excesses at late times (t >= 100 d). H- and K-band emission from these objects is dominated by a continuum that rises toward longer wavelengths. The data are interpreted as thermal emission from dust, probably situated in a pre-existing circumstellar nebula. The IR luminosities implied by single temperature blackbody fits are quite large,> 10^(41 - 42) erg s^-1, and the emission evolves slowly, lasting for years after maximum light. For SN 1995N, the integrated energy release via IR dust emission was 0.5 -- 1 * 10^50 erg. A number of dust heating scenarios are considered, the most likely being an infrared echo poweredby X-ray and UV emissions from the shock interaction with a dense circumstellar medium.Comment: 14 Pages, 3 Figures, Accecpted for publication in The Astrophysical Journa

The influence of disease categories on gene candidate predictions from model organism phenotypes

Background The molecular etiology is still to be identified for about half of the currently described Mendelian diseases in humans, thereby hindering efforts to find treatments or preventive measures. Advances, such as new sequencing technologies, have led to increasing amounts of data becoming available with which to address the problem of identifying disease genes. Therefore, automated methods are needed that reliably predict disease gene candidates based on available data. We have recently developed Exomiser as a tool for identifying causative variants from exome analysis results by filtering and prioritising using a number of criteria including the phenotype similarity between the disease and mouse mutants involving the gene candidates. Initial investigations revealed a variation in performance for different medical categories of disease, due in part to a varying contribution of the phenotype scoring component. Results In this study, we further analyse the performance of our cross-species phenotype matching algorithm, and examine in more detail the reasons why disease gene filtering based on phenotype data works better for certain disease categories than others. We found that in addition to misleading phenotype alignments between species, some disease categories are still more amenable to automated predictions than others, and that this often ties in with community perceptions on how well the organism works as model. Conclusions In conclusion, our automated disease gene candidate predictions are highly dependent on the organism used for the predictions and the disease category being studied. Future work on computational disease gene prediction using phenotype data would benefit from methods that take into account the disease category and the source of model organism data

Detection of CO and Dust Emission in Near-Infrared Spectra of SN 1998S

Near-infrared spectra (0.95 -- 2.4 micron) of the peculiar Type IIn supernova 1998S in NGC 3877 from 95 to 355 days after maximum light are presented. K-band data taken at days 95 and 225 show the presence of the first overtone of CO emission near 2.3 micron, which is gone by day 355. An apparent extended blue wing on the CO profile in the day 95 spectrum could indicate a large CO expansion velocity (~2000 -- 3000 km/s). This is the third detection of infrared CO emission in nearly as many Type II supernovae studied, implying that molecule formation may be fairly common in Type II events, and that the early formation of molecules in SN 1987A may be typical rather than exceptional. Multi-peak hydrogen and helium lines suggest that SN 1998S is interacting with a circumstellar disk, and the fading of the red side of this profile with time is suggestive of dust formation in the ejecta, perhaps induced by CO cooling. Continuum emission that rises towards longer wavelengths (J -> K) is seen after day 225 with an estimated near-infrared luminosity >~ 10^40 erg/s. This may be related to the near-infrared excesses seen in a number of other supernovae. If this continuum is due to free-free emission, it requires an exceptionally shallow density profile. On the other hand, the shape of the continuum is well fit by a 1200 +- 150 K blackbody spectrum possibly due to thermal emission from dust. Interestingly, we observe a similar 1200 K blackbody-like, near-infrared continuum in SN 1997ab, another Type IIn supernova at an even later post-maximum epoch (day 1064+). A number of dust emission scenarios are discussed, and we conclude that the NIR dust continuum is likely powered by the interaction of SN 1998S with the circumstellar medium.Comment: 38 Pages, 12 Figures, Submitted to The Astronomical Journa

Techniques for mesoappendix transection and appendix resection: insights from the ESTES SnapAppy study

Introduction: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications. Material and methods: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). Results: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90 days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41-0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11-0.96), p = 0.045] complications could be detected when using energy devices. Conclusions: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts

Modeling seizures in the Human Phenotype Ontology according to contemporary ILAE concepts makes big phenotypic data tractable.

OBJECTIVE: The clinical features of epilepsy determine how it is defined, which in turn guides management. Therefore, consideration of the fundamental clinical entities that comprise an epilepsy is essential in the study of causes, trajectories, and treatment responses. The Human Phenotype Ontology (HPO) is used widely in clinical and research genetics for concise communication and modeling of clinical features, allowing extracted data to be harmonized using logical inference. We sought to redesign the HPO seizure subontology to improve its consistency with current epileptological concepts, supporting the use of large clinical data sets in high-throughput clinical and research genomics. METHODS: We created a new HPO seizure subontology based on the 2017 International League Against Epilepsy (ILAE) Operational Classification of Seizure Types, and integrated concepts of status epilepticus, febrile, reflex, and neonatal seizures at different levels of detail. We compared the HPO seizure subontology prior to, and following, our revision, according to the information that could be inferred about the seizures of 791 individuals from three independent cohorts: 2 previously published and 150 newly recruited individuals. Each cohort\u27s data were provided in a different format and harmonized using the two versions of the HPO. RESULTS: The new seizure subontology increased the number of descriptive concepts for seizures 5-fold. The number of seizure descriptors that could be annotated to the cohort increased by 40% and the total amount of information about individuals\u27 seizures increased by 38%. The most important qualitative difference was the relationship of focal to bilateral tonic-clonic seizure to generalized-onset and focal-onset seizures. SIGNIFICANCE: We have generated a detailed contemporary conceptual map for harmonization of clinical seizure data, implemented in the official 2020-12-07 HPO release and freely available at hpo.jax.org. This will help to overcome the phenotypic bottleneck in genomics, facilitate reuse of valuable data, and ultimately improve diagnostics and precision treatment of the epilepsies