Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

Study of wave motion on the emergence of veering, locking, and coupling in periodic composite panels.

This research proposes the effect of micropolar-Cosserat (MC) parameters (length-scale parameters and Cosserat shear modulus) on the dispersion characteristics of propagating wave modes in periodic composite panels (PCPs). These inbuilt parameters are due to the assumption of the length-scale boundary conditions that allow for capturing the micro-rotational (MR) wave mode along with the flexural ones. A significant contribution of this study is the transformation of the two-dimensional (2-D) periodic composite problem into a series of one-dimensional (1-D) ones using the MC continuum theory. The analysis employs the transfer matrix method in the framework of the state-space approach to investigate periodic systems in the eigenvalue domain. Additionally, Bloch-Floquet's periodic boundary conditions (PBCs) are applied to the unit cell to ensure the periodicity of the system. The main innovation lies in observing veering, locking, and coupling phenomena, which occur due to alterations in lamina orientation and MC parameters. Moreover, the presence of inbuilt parameters renders the dispersion characteristics highly sensitive to even minor coefficient variations, with a mere 1% change significantly impacting eigenmode fluctuations. The sudden bandgap (BG) disappearing nature could be used to identify the accurate value of the coefficient for designing and analyzing PCPs.

On the estimation of the effect of weight change on a health outcome using observational data, by utilising the target trial emulation framework.

BACKGROUND/OBJECTIVES: When studying the effect of weight change between two time points on a health outcome using observational data, two main problems arise initially (i) 'when is time zero?' and (ii) 'which confounders should we account for?' From the baseline date or the 1st follow-up (when the weight change can be measured)? Different methods have been previously used in the literature that carry different sources of bias and hence produce different results. METHODS: We utilised the target trial emulation framework and considered weight change as a hypothetical intervention. First, we used a simplified example from a hypothetical randomised trial where no modelling is required. Then we simulated data from an observational study where modelling is needed. We demonstrate the problems of each of these methods and suggest a strategy. INTERVENTIONS: weight loss/gain vs maintenance. RESULTS: The recommended method defines time-zero at enrolment, but adjustment for confounders (or exclusion of individuals based on levels of confounders) should be performed both at enrolment and the 1st follow-up. CONCLUSIONS: The implementation of our suggested method [adjusting for (or excluding based on) confounders measured both at baseline and the 1st follow-up] can help researchers attenuate bias by avoiding some common pitfalls. Other methods that have been widely used in the past to estimate the effect of weight change on a health outcome are more biased. However, two issues remain (i) the exposure is not well-defined as there are different ways of changing weight (however we tried to reduce this problem by excluding individuals who develop a chronic disease); and (ii) immortal time bias, which may be small if the time to first follow up is short.

Local and Nonlocal Transport Spectroscopy in Planar Josephson Junctions.

We report simultaneously acquired local and nonlocal transport spectroscopy in a phase-biased planar Josephson junction based on an epitaxial InAs-Al hybrid two-dimensional heterostructure. Quantum point contacts at the junction ends allow measurement of the 2×2 matrix of local and nonlocal tunneling conductances as a function of magnetic field along the junction, phase difference across the junction, and carrier density. A closing and reopening of a gap was observed in both the local and nonlocal tunneling spectra as a function of magnetic field. For particular tunings of junction density, gap reopenings were accompanied by zero-bias conductance peaks (ZBCPs) in local conductances. End-to-end correlation of gap reopening was strong, while correlation of local ZBCPs was weak. A model of the device, with disorder treated phenomenologically, shows comparable conductance matrix behavior associated with a topological phase transition. Phase dependence helps distinguish possible origins of the ZBCPs.

Cardiovascular mortality in Brazil during the COVID-19 pandemic: a comparison between underlying and multiple causes of death.

OBJECTIVES: The COVID-19 pandemic has differentially impacted cardiovascular disease (CVD) mortality worldwide. Causes of death misclassification may be one of the reasons. We evaluated the impact of the pandemic on CVD mortality in Brazil, comparing underlying causes (UCs) and multiple causes (MCs) of death. STUDY DESIGN: Ecological time-series study. METHODS: An ecological, time-series study was conducted analysing age-standardised death rates for CVD, from epidemiological week (EW) 10/2020 to 39/2021, using data from the Mortality Information System, Brazil. CVD was defined using the International Classification of Diseases (ICD-10) coding, if reported as UC or MC of death. Observed and expected data (mean for the same EW, 2017-2019) were compared. Risk ratios (RiRs) were analysed, and 95% confidence intervals (CIs) were calculated. RESULTS: Age-standardised mortality rate for CVD as UC of death was 165.8 (95%CI: 165.4-166.3) per 100,000 inhabitants, similar to what was expected (165.6/100,000, 95%CI: 165.2-166.1, RiR = 1.00). There was increased out-of-hospital mortality (RiR = 1.18; 95%CI: 1.17-1.19) and deaths of ill-defined causes (RiR = 1.43; 95%CI: 1.42-1.44). The increase in out-of-hospital deaths was more pronounced in the North (RiR = 1.33; 95%CI 1.30-1.36) region, with a less resilient health system. Conversely, as MCs of death, there was a 10% increase in CVD mortality (observed: 243.2 [95%CI: 242.7-243.7], expected: 221.6 [95%CI: 221.1-222.1] per 100,000). An increase also occurred in the North and Central West regions (RiR = 1.16; 95%CI: 1.15-1.18), among men (RiR = 1.11; 95%CI: 1.11-1.12) and individuals aged ≥60 years (RiR = 1.11; 95%CI: 1.10-1.11). CONCLUSIONS: During the pandemic, mortality rates for CVD as MCs of death increased in Brazil, whereas as UC mortality rates did not change. Higher out-of-hospital mortality, misclassification, and competing causes of death may explain this pattern.

Morphology of human fetal enteric neurons: A comparative study of different segments of the colon.

OBJECTIVES: The Enteric Nervous System (ENS) present in the wall of the gut is currently being explored because of its influence on the gut and beyond. In this context, the morphology of developing ENS has not been completely understood in humans due to lack of adequate literature. The aim of the present study was to observe the morphology of the enteric neurons in the human fetal colon and compare the findings in ascending colon a midgut derivative and descending colon a hindgut derivative at various weeks of gestation (WG). MATERIAL AND METHODS: Tissue samples from 15 aborted fetuses (11 WG to 2 months postnatal) were processed for Cresyl violet, H & E staining, and NADPH Diaphorase histochemistry. The morphometric analysis was done by calculating the neuronal number density and neuronal fractional area. The Student t-test; Mann-Whitney test and Wilcoxon signed-rank test were used to analyze the data. RESULTS: The muscularis externa with two distinct layers was visible as early as 13 WG and the muscularis mucosae was first observed at 18 WG. The size of the myenteric neurons appeared to be larger with increasing weeks of gestation suggesting a process of neuronal maturation. The neuronal number density and neuronal fractional area seemed to be reduced with advancing fetal age. There was no marked difference between the ascending and sigmoid colon. At 23 and 26 WG, a mature pattern of nitrergic innervation was observed. CONCLUSION: This study is done on human fetal tissue samples unlike previous studies on animal samples to comprehend the morphology of developing ENS. It will aid in understanding the effect of ENS on various neurological disorders.

Search for Dark-Matter-Induced Oscillations of Fundamental Constants Using Molecular Spectroscopy.

A possible implication of an ultralight dark matter field interacting with the standard model degrees of freedom is oscillations of fundamental constants. Here, we establish direct experimental bounds on the coupling of an oscillating ultralight dark matter field to the up, down, and strange quarks and to the gluons, for oscillation frequencies between 10 and 10^{8} Hz. We employ spectroscopic experiments that take advantage of the dependence of molecular transition frequencies on the nuclear masses. Our results apply to previously unexplored frequency bands and improve on existing bounds at frequencies >5 MHz. We also improve on the bounds for coupling to the electromagnetic field and the electron field, in particular spectral windows. We identify a sector of ultralight dark matter and standard model coupling space where the bounds from equivalence principle tests may be challenged by next-generation experiments of the present kind.

Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes.

Autism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy and relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation of fMRI-based connectivity in the mouse, in which specific ASD-relevant mutations can be isolated and modeled minimizing environmental contributions. By performing brain-wide connectivity mapping across 16 mouse mutants, we show that different ASD-associated etiologies cause a broad spectrum of connectional abnormalities in which diverse, often diverging, connectivity signatures are recognizable. Despite this heterogeneity, the identified connectivity alterations could be classified into four subtypes characterized by discrete signatures of network dysfunction. Our findings show that etiological variability is a key determinant of connectivity heterogeneity in ASD, hence reconciling conflicting findings in clinical populations. The identification of etiologically-relevant connectivity subtypes could improve diagnostic label accuracy in the non-syndromic ASD population and paves the way for personalized treatment approaches.

Reproducibility of assessment of full-dilatation Cesarean section scar in women undergoing second-trimester screening for preterm birth.

OBJECTIVE: To assess the reproducibility of a standardized method of measuring the Cesarean section (CS) scar, CS scar niche and their position relative to the internal os of the uterine cervix by transvaginal ultrasound in pregnant women with a previous full-dilatation CS. METHODS: This was a prospective, single-center reproducibility study on women with a singleton pregnancy and a previous full-dilatation CS who underwent transvaginal ultrasound assessment of cervical length and CS scar characteristics at 14-24 weeks' gestation. The CS scar was identified as a hypoechogenic linear discontinuity of the myometrium at the anterior wall of the lower uterine segment or cervix. The CS scar niche was identified as an indentation at the site of the scar with a depth of at least 2 mm. The CS scar position was evaluated by measuring the distance to the internal cervical os. CS scar niche parameters, including its length, depth, width, and residual and adjacent myometrial thickness, were assessed in the sagittal and transverse planes. Qualitative reproducibility was assessed by agreement regarding visibility of the CS scar and niche. Quantitative reproducibility of CS scar measurements was assessed using three sets of images: (1) real-time two-dimensional (2D) images (real-time acquisition and caliper placement on 2D images by two operators), (2) offline 2D still images (offline caliper placement by two operators on stored 2D images acquired by one operator) and (3) three-dimensional (3D) volume images (volume manipulation and caliper placement on 2D images extracted by two operators). Agreement on CS scar visibility and the presence of a niche was analyzed using kappa coefficients. Intraobserver and interobserver reproducibility of quantitative measurements was assessed using Bland-Altman plots. RESULTS: To achieve the desired statistical power, 72 women were recruited. The CS scar was visualized in > 80% of images. Interobserver agreement for scar visualization and presence of a niche in real-time 2D images was excellent (kappa coefficients of 0.84 and 0.85, respectively). Overall, reproducibility was higher for real-time 2D and offline 2D still images than for 3D volume images. The 95% limits of agreement (LOA) for intraobserver reproducibility were between ± 1.1 and ± 3.6 mm for all sets of images; the 95% LOA for interobserver reproducibility were between ± 2.0 and ± 6.3 mm. Measurement of the distance from the CS scar to the internal cervical os was the most reproducible 2D measurement (intraobserver and interobserver 95% LOA within ± 1.6 and ± 2.7 mm, respectively). Overall, niche measurements were the least reproducible measurements (intraobserver 95% LOA between ± 1.6 and ± 3.6 mm; interobserver 95% LOA between ± 3.1 and ± 6.3 mm). There was no consistent difference between measurements obtained by reacquisition of 2D images (planes obtained twice and caliper placed), caliper placement on 2D stored images or volume manipulation (planes obtained twice and caliper placed). CONCLUSIONS: The CS scar position and scar niche in pregnant women with a previous full-dilatation CS can be assessed in the second trimester of a subsequent pregnancy using either 2D or 3D volume ultrasound imaging with a high level of reproducibility. Overall, the most reproducible CS scar parameter is the distance from the CS scar to the internal cervical os. The method proposed in this study should enable clinicians to assess the CS scar reliably and may help predict pregnancy outcome. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Characterizing the relationships between patient-reported outcomes and clinician assessments of alopecia areata in a phase 2a randomized trial of ritlecitinib and brepocitinib.

BACKGROUND: The phase 2a ALLEGRO trial (NCT02974868) investigated the safety and efficacy of ritlecitinib (PF-06651600) and brepocitinib (PF-06700841) in adults with alopecia areata. No randomized controlled trial for alopecia areata has evaluated correlations between clinician-assessed hair loss and patient-reported outcomes. OBJECTIVES: Report scores from the Alopecia Areata Symptom Impact Scale (AASIS; a patient-reported outcome tool) and explore the relationships of those scores with clinician-assessed Severity of Alopecia Tool (SALT) scores at baseline and week 24 of the ALLEGRO trial. METHODS: Adults with alopecia areata were randomized to ritlecitinib (n = 48), brepocitinib (n = 47) or placebo (n = 47). After 24 weeks, the mixed-effects model with repeated measures was used to calculate the active treatment groups' AASIS score least-squares mean differences. Relationships between AASIS and SALT scores at baseline and week 24 were evaluated by Pearson's correlation coefficients using pooled data. RESULTS: Baseline AASIS and SALT scores were similar among treatment groups. Both active treatment groups reported significant improvements in AASIS scores at week 24 (least-squares mean differences vs. placebo for ritlecitinib, -0.8 to -2.3; brepocitinib, -0.9 to -3.7; P < 0.05 for all). At week 24, the mean SALT scores (standard deviation) improved compared with baseline [ritlecitinib, 54.4 (40.3) vs. 89.4 (15.8); brepocitinib, 31.9 (35.7) vs. 86.4 (18.1)]. The correlation coefficients between AASIS global and subscale scores and SALT scores at week 24 ranged from 0.34 to 0.58; P < 0.05 for all. CONCLUSIONS: Patients randomized to ritlecitinib or brepocitinib reported significantly improved AASIS and SALT scores at week 24 of the ALLEGRO trial compared to placebo. At week 24, medium-to-large correlations can be seen between AASIS global and subscale scores and SALT scores. Our experience with AASIS instrument highlighted several aspects that suggest new patient-reported outcome tools are needed to accurately assess patients' relevant alopecia areata related signs, symptoms and daily functioning.

Predictors of self-management in patients with chronic low back pain: a longitudinal study.

BACKGROUND: Self-management (SM) is a key recommended strategy for managing chronic low back pain (CLBP). However, SM programmes generate small to moderate benefits for reducing pain and disability in patients with CLBP. The benefits of the SM programme can potentially be optimised by identifying specific subgroups of patients who are the best responders. To date, no longitudinal study has examined the predictive relationships between SM and biopsychosocial factors in patients with CLBP. The aim was to determine whether biopsychosocial factors predict SM and its change over time in patients with CLBP. METHODS: In this multi-centre longitudinal cohort study, we recruited 270 working-age patients with CLBP (mean age 43.74, 61% female) who consulted outpatient physiotherapy for their CLBP. Participants completed self-reported validated measures of pain intensity, disability, physical activity, kinesiophobia, catastrophising, depression and SM at baseline and six months. SM constructs were measured using eight subscales of the Health Education Impact Questionnaire (heiQ), including Health Directed Activity (HDA), Positive and Active Engagement in Life (PAEL), Emotional Distress (ED), Self-Monitoring and Insight (SMI), Constructive Attitudes and Approaches (CAA), Skill and Technique Acquisition (STA), Social Integration and Support (SIS) and Health Service Navigation (HSN). Data were analysed using General Linear Model (GLM) regression. RESULTS: Physical activity and healthcare use (positively) and disability, depression, kinesiophobia, catastrophising (negatively) predicted (p < 0.05, R2 0.07-0.55) SM constructs at baseline in patients with CLBP. Baseline depression (constructs: PAEL, ED, SMI, CAA and STA), kinesiophobia (constructs: CAA and HSN), catastrophising (construct: ED), and physical disability (constructs: PAEL, CAA and SIS) negatively predicted a range of SM constructs. Changes over six months in SM constructs were predicted by changes in depression, kinesiophobia, catastrophising, and physical activity (p < 0.05, R2 0.13-0.32). CONCLUSIONS: Self-reported disability, physical activity, depression, catastrophising and kinesiophobia predicted multiple constructs of SM measured using the heiQ subscales in working-age patients with CLBP. Knowledge of biopsychosocial predictors of SM may help triage patients with CLBP into targeted pain management programmes. TRIAL REGISTRATION: The study protocol was registered at ClinicalTrials.gov on 22 December 2015 (ID: NCT02636777).

Real-world study of multiple naloxone administration for opioid overdose reversal among bystanders.

BACKGROUND: The increasing prevalence of highly potent, illicitly manufactured fentanyl and its analogues (IMF) in the USA is exacerbating the opioid epidemic which has worsened during the COVID-19 pandemic. Narcan® (naloxone HCl) Nasal Spray has been approved by the US Food and Drug Administration as a treatment for opioid-related overdoses. Due to the high potency of IMF, multiple naloxone administrations (MNA) may be needed per overdose event. It is essential to determine the patterns of naloxone use, including MNA, and preferences among bystanders who have used naloxone for opioid overdose reversal. METHODS: A cross-sectional web-based survey was administered to 125 adult US residents who administered 4 mg Narcan® Nasal Spray during an opioid overdose in the past year. The survey asked about the most recent overdose event, the use of Narcan® during the event and the associated withdrawal symptoms, and participant preferences regarding dosages of naloxone nasal spray. An open-ended voice survey was completed by 35 participants. RESULTS: Participants were mostly female (70%) and white (78%), while reported overdose events most frequently occurred in people who were males (54%) and white (86%). Most events (95%) were successfully reversed, with 78% using ≥ 2 doses and 30% using ≥ 3 doses of Narcan® Nasal Spray. Over 90% were worried that 1 Narcan® box may not be enough for a successful future reversal. Reported withdrawal symptoms were similar in overdose events where 1 versus ≥ 2 sprays were given. Eighty-six percent of participants reported more confidence in an 8 mg versus a 4 mg naloxone nasal spray and 77% reported a stronger preference for 8 mg over 4 mg. CONCLUSIONS: MNA occurred in most overdose events, often involving more sprays than are provided in one Narcan® nasal spray box, and participants predominantly expressed having a stronger preference for and confidence in an 8 mg compared to a 4 mg nasal spray. This suggests the need and desire for a higher dose naloxone nasal spray formulation option. Given that bystanders may be the first to administer naloxone to someone experiencing an opioid overdose, ensuring access to an adequate naloxone supply is critical in addressing the opioid overdose epidemic.

The need for multiple naloxone administrations for opioid overdose reversals: A review of the literature.

Background A growing challenge in the opioid epidemic is the rise of highly potent synthetic opioids, (i.e., illicitly manufactured fentanyl [IMF]) entering the US non-prescription opioid market. Successful reversal may require multiple doses of naloxone, the standard of care for opioid overdose. We conducted a narrative literature review to summarize the rates of multiple naloxone administrations (MNA) for opioid overdose reversal. Methods: A MEDLINE search was conducted for published articles using MESH search terms: opioid overdose, naloxone and multiple naloxone administration. Of the 2,101 studies identified, articles meeting inclusion/exclusion criteria were reviewed, categorized by primary and secondary outcomes of interest and summarized by data source and study design. Results: A total of 24 articles meeting eligibility criteria were included. Among EMS-based studies, MNA rates ranged from 9% to 53%; in general, bystander-reported studies were notably higher, from 16% to 89%. Variation in study design, data sources, year and geography, may have contributed to these ranges. Three studies that included longitudinal results reported a significant percent increase between 26% and 43% in annual MNA rates or a significant increase in mean naloxone doses over time (p < .001). Conclusions: This summary found that multiple naloxone administrations during opioid overdose encounters vary widely, have occurred in up to 89% of all opioid overdoses, and have significantly increased over time. Higher naloxone formulations may fulfill an unmet need in opioid overdose reversals, given the rising rates of overdoses involving IMF. Further studies are needed to gain a better understanding of MNA during opioid overdose encounters, particularly across a wider geographic region in the US in order to inform continuing efforts to combat the opioid epidemic.

Real-world study of multiple naloxone administrations for opioid overdose reversal among emergency medical service providers.

Background: The increasing rates of highly potent, illicit synthetic opioids (i.e., fentanyl) in the US is exacerbating the ongoing opioid epidemic. Multiple naloxone administrations (MNA) may be required to successfully reverse opioid overdoses. We conducted a real-world study to assess the rate of MNA for opioid overdose and identify factors associated with MNA. Methods: Data from the 2015-2020 National Emergency Medical Services Information System was examined to determine trends in events requiring MNA. Logistic regression analysis was performed to determine factors associated with MNA. Results: The percentage of individuals receiving MNA increased from 18.4% in 2015 to 28.4% in 2020. The odds of an event requiring MNA significantly increased by 11% annually. The adjusted odds ratio (aOR) for MNA were greatest among males, when advanced life support (ALS) was provided, and when the dispatch complaint indicated there was a drug poisoning event. Conclusions: The 54% increase in MNA since 2015 parallels the rise in overdose deaths attributable to synthetic opioids. This growth is visible in all regions of the country, including the West, where the prevalence of illicitly manufactured synthetic opioids is intensifying. Given this phenomenon, higher naloxone formulations may fulfill an unmet need in addressing the opioid overdose crisis.

Active microrheology using pulsed optical tweezers to probe viscoelasticity of lamin A.

Lamins are nucleoskeletal proteins of mammalian cells that stabilize the structure and maintain the rigidity of the nucleus. These type V intermediate filament proteins which are predominantly of A and B types provide necessary tensile strength to the nucleus. Single amino acid missense mutations occurring all over the lamin A protein form a cluster of human diseases termed as laminopathies, most of which principally affect the muscle and cardiac tissues responsible for load bearing functionalities of the body. One such mutation is A350P which causes dilated cardiomyopathy in patients. It is postulated that a change from alanine to proline in the α-helical coiled-coil forming 2B rod domain of the protein might severely disrupt the propensity of the filaments to polymerise into functional higher order structures required to form a fully functional lamina with its characteristic elasticity. In this study, we have elucidated for the very first time, the application of active microrheology employing oscillating optical tweezers to investigate any alterations in the viscoelastic parameters of the mutant protein meshwork in vitro, which might translate into possible changes in nuclear plasticity. We confirmed our findings from this robust yet fast method by imaging both the wild type and mutant lamin A networks using a super resolution microscope, and observed changes in the mesh size which corroborate our measured changes in the viscoelastic parameters of the lamins. This method could thus be extended to conduct microrheological measurements on any intermediate filament protein thus bearing significant implications in laminopathies and other diseases associated with intermediate filaments.

Observational study of clinico-radiological follow-up of COVID-19 pneumonia: a district general hospital experience in the UK.

BACKGROUND: The British Thoracic Society (BTS) recommends that all patients admitted with COVID-19 pneumonia should have a chest X-ray (CXR) and clinical follow-up at 6 or 12 weeks, depending on the disease severity. Little data is available on long-term CXR follow-up for moderate and severe COVID-19 pneumonia. This study aims to evaluate compliance with clinico-radiological follow-up of patients recovering from COVID-19 pneumonia at a local hospital in the UK, as per the BTS guidance, and to analyse radiological changes at clinical follow-up at 12 weeks, in order to risk-stratify and improve patient outcomes. METHODS: This is a single-centre retrospective audit of 255 consecutive COVID-19 positive patients admitted to a local hospital in the UK over 5 months between May and October 2020. All CXRs and clinic follow-up at 12 ± 8 weeks were checked on an electronic database. RESULTS: Over one in two (131/255) patients had CXR evidence of COVID-19 pneumonia during the initial hospital admission. Half of the patients (60/131) died before CXR or clinic follow-up. Fifty-eight percent (41/71) of the surviving patients had a follow-up CXR, and only two developed respiratory complications- one had residual lung fibrosis, another a pulmonary embolism. Eighty-eight percent (36/41) of the patients had either resolution or improved radiological changes at follow-up. Most patients who had abnormal follow-up CXR were symptomatic (6/8), and many asymptomatic patients at follow-up had a normal CXR (10/12). CONCLUSIONS: Although there were concerns about interstitial lung disease (ILD) incidence in patients with COVID-19 pneumonia, most of our patients with COVID-19 pneumonia had no pulmonary complications at follow-up with CXR. This emphasises that CXR, a cost-effective investigation, can be used to risk-stratify patients for long term pulmonary complications following their COVID-19 pneumonia. However, we acknowledge the limitations of a low CXR and clinic follow-up rate in our cohort.

A large outbreak of measles in the West Midlands, England, 2017-2018: descriptive epidemiology, control measures and lessons learnt.

In November 2017, eight confirmed measles cases were reported to Public Health England from a hospital in the West Midlands. A multidisciplinary Incident Management Team (IMT) was established to determine the extent of the problem and coordinate an outbreak response. Between 1 November 2017 and 4 June 2018, a total of 116 confirmed and 21 likely measles cases were linked to this outbreak; just under half (43%) were aged over 15 years of age. Fifty-five of the confirmed cases were hospitalised (48%) and no deaths were reported. At the start of the outbreak, cases were mostly individuals of Romanian origin; the outbreak subsequently spread to the wider population. Over the 8-month response, the IMT conducted the following control measures: extensive contact tracing, immediate provision of post-exposure prophylaxis, community engagement amongst specific high-risk groups, MMR awareness raising including catch-up campaigns and enhanced vaccination services at selected GP surgeries. Key challenges to the effective control measures included language difficulties limiting community engagement; delays in diagnosis, notification and appropriate isolation of cases; limited resources for contact tracing across multiple high-risk settings (including GPs and hospitals) and lack of timely data on vaccine coverage in sub-groups of the population to guide public health action.

Obesity during the COVID-19 pandemic: both cause of high risk and potential effect of lockdown? A population-based electronic health record study.

OBJECTIVES: Obesity is a modifiable risk factor for coronavirus disease 2019 (COVID-19)-related mortality. We estimated excess mortality in obesity, both 'direct', through infection, and 'indirect', through changes in health care, and also due to potential increasing obesity during lockdown. STUDY DESIGN: The study design of this study is a retrospective cohort study and causal inference methods. METHODS: In population-based electronic health records for 1,958,638 individuals in England, we estimated 1-year mortality risk ('direct' and 'indirect' effects) for obese individuals, incorporating (i) pre-COVID-19 risk by age, sex and comorbidities, (ii) population infection rate and (iii) relative impact on mortality (relative risk [RR]: 1.2, 1.5, 2.0 and 3.0). Using causal inference models, we estimated impact of change in body mass index (BMI) and physical activity during 3-month lockdown on 1-year incidence for high-risk conditions (cardiovascular diseases, diabetes, chronic obstructive pulmonary disease and chronic kidney disease), accounting for confounders. RESULTS: For severely obese individuals (3.5% at baseline), at 10% population infection rate, we estimated direct impact of 240 and 479 excess deaths in England at RR 1.5 and 2.0, respectively, and indirect effect of 383-767 excess deaths, assuming 40% and 80% will be affected at RR = 1.2. Owing to BMI change during the lockdown, we estimated that 97,755 (5.4%: normal weight to overweight, 5.0%: overweight to obese and 1.3%: obese to severely obese) to 434,104 individuals (15%: normal weight to overweight, 15%: overweight to obese and 6%: obese to severely obese) would be at higher risk for COVID-19 over one year. CONCLUSIONS: Prevention of obesity and promotion of physical activity are at least as important as physical isolation of severely obese individuals during the pandemic.

An oxygen-rich atmosphere or systemic fluoxetine extend the time to respiratory arrest in a rat model of obstructive apnea.

Audiogenic seizure-prone mice can be protected from seizure-associated death by exposure to an oxygen atmosphere or treatment with selective serotonergic reuptake inhibitors (SSRIs). We have shown previously in a rat model that epileptic seizure activity can spread through brainstem areas to cause sufficient laryngospasm for obstructive apnea and that the period of seizure-associated obstructive apnea can last long enough for respiratory arrest to occur. We hypothesized that both the oxygen-rich atmosphere and SSRIs function by prolonging the time to respiratory arrest, thus ensuring that seizure activity stops before the point of respiratory arrest to allow recovery of respiratory function. To test this hypothesis, we evaluated each preventative treatment in a rat model of controlled airway occlusion where the times to respiratory arrest can be measured. Adult male Sprague Dawley rats (median age = 66 days) were studied in the absence of any seizure activity. By directly studying responses to controlled airway occlusion, rather than airway occlusion secondary to seizure activity, we could isolate the effects of manipulations that might prolong respiratory arrest from the effects of those manipulations on seizure intensity. All group sizes were ≥ 8 animals per group. We found that both oxygen exposure and fluoxetine significantly increased the time to respiratory arrest by up to 65% (p < .0001 for 5 min oxygen exposure; p = .031 for 25 mg/kg fluoxetine tested 60 min after injection) and, given that neither treatment has been shown to significantly alter seizure duration, these increases can account for the protection of either manipulation against death in sudden death models. Importantly, we found that 30 s of exposure to oxygen produced nearly the same protection as 5 min exposure suggesting that oxygen exposure could start after a seizure starts (p = .0012 for 30 s oxygen exposure). Experiments with 50% oxygen/50% air mixtures indicate that the oxygen concentration needs to be above about 60% to ensure that times to respiratory arrest will always be longer than a period of seizure-induced airway occlusion. Selective serotonin reuptake inhibitors, while instructive with regard to mechanism, require impractical dosing and may carry additional risk in the form of greater challenges for resuscitation. We conclude that oxygen exposure or SSRI treatment prevent seizure associated death by sufficiently prolonging the time to respiratory arrest so that respiratory function can recover after the seizure abates and eliminates the stimulus for seizure-induced apnea.

Facilitators of behavior change and weight loss in an intervention for African American Breast Cancer Survivors.

PURPOSE: The purpose of this study was to examine facilitators of behavior change and weight loss among African-American women who participated in the Moving Forward Efficacy trial. METHODS: Linear mixed models were used to examine the role of self-efficacy, social support, and perceived access to healthy eating, exercise, and neighborhood safety on weight, physical activity, and diet. We also examined the mediation of self-efficacy, social support, and perceived access to healthy eating, exercise, and neighborhood safety on weight loss, physical activity, and diet using the Freedman Schatzkin statistic. RESULTS: We found no evidence to suggest mediation, but some direct associations of self-efficacy, certain types of social support and perceived access to exercise on weight loss, and behavior change. CONCLUSION: We determined that self-efficacy, social support, and perceived access to exercise played a role in weight loss, increased MVPA, and better diet. The role of self-efficacy and perceived access to exercise were more consistent than social support.