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Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research.

Funder: UK Health Data Research BREATHE Hub, BACKGROUND: Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation. METHODS: PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness. RESULTS: We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21). CONCLUSIONS: Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.

Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders.

On 2018 Feb. 4.41, the All-Sky Automated Survey for SuperNovae (ASAS-SN) discovered ASASSN-18bt in the K2 Campaign 16 field. With a redshift of z=0.01098 and a peak apparent magnitude of B_{max}=14.31, ASASSN-18bt is the nearest and brightest SNe Ia yet observed by the Kepler spacecraft. Here we present the discovery of ASASSN-18bt, the K2 light curve, and pre-discovery data from ASAS-SN and the Asteroid Terrestrial-impact Last Alert System (ATLAS). The K2 early-time light curve has an unprecedented 30-minute cadence and photometric precision for an SN~Ia light curve, and it unambiguously shows a ~4 day nearly linear phase followed by a steeper rise. Thus, ASASSN-18bt joins a growing list of SNe Ia whose early light curves are not well described by a single power law. We show that a double-power-law model fits the data reasonably well, hinting that two physical processes must be responsible for the observed rise. However, we find that current models of the interaction with a non-degenerate companion predict an abrupt rise and cannot adequately explain the initial, slower linear phase. Instead, we find that existing, published models with shallow 56Ni are able to span the observed behavior and, with tuning, may be able to reproduce the ASASSN-18bt light curve. Regardless, more theoretical work is needed to satisfactorily model this and other early-time SNe~Ia light curves. Finally, we use Swift X-ray non-detections to constrain the presence of circumstellar material (CSM) at much larger distances and lower densities than possible with the optical light curve. For a constant density CSM these non-detections constrain rho, 17 pages, 8 figures, 3 Tables. Accepted to ApJ. This work is part of a number of papers analyzing ASASSN-18bt, with coordinated papers from Dimitriadis et al. (2018) and Li et al. (2018)

Mandibular reconstruction in osteoradionecrosis or salvage surgery can often be complicated by the lack of suitable recipient vessels in the ipsilateral neck and the associated requirement for significant extraoral skin reconstruction. The scapula tip with its long vascular pedicle and option of a chimeric soft tissue component offers a versatile reconstructive solution in such cases. This article reports four consecutive cases of mandibular reconstruction with poor ipsilateral vascular options and additional soft tissue requirements in which the scapula tip was justified and preferred. The blood supply to the lateral scapula through the circumflex scapular system is well established in the literature and this would be the preferred reconstruction in class I mandibular defects associated with a significant soft tissue requirement. The scapula tip would suit cases where the ipsilateral recipient vessels are compromised, and so justify the potential for mandibular reconstruction with inferior bone stock.

Germline aberrations in critical DNA-repair and DNA damage-response (DDR) genes cause cancer predisposition, whereas various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality can be exploited in such malignancies, as exemplified by approval of poly(ADP-ribose) polymerase inhibitors for treating BRCA1/2-mutated ovarian cancers. Herein, we detail how cellular DDR processes engage various proteins that sense DNA damage, initiate signaling pathways to promote cell-cycle checkpoint activation, trigger apoptosis, and coordinate DNA repair. We focus on novel therapeutic strategies targeting promising DDR targets and discuss challenges of patient selection and the development of rational drug combinations. $\textbf{SIGNIFICANCE}$: Various inhibitors of DDR components are in preclinical and clinical development. A thorough understanding of DDR pathway complexities must now be combined with strategies and lessons learned from the successful registration of PARP inhibitors in order to fully exploit the potential of DDR inhibitors and to ensure their long-term clinical success. Cancer Discov; 7(1); 20-37. ©2016 AACR

BACKGROUND Recent discussions about securing the autonomy and safety of older people in a cost-effective way have culminated in the establishment of "Silver Alert" media-alert policies in more than half of US states over the past 5 years. Although these policies have been established with exceptional legislative speed, research has not yet examined how these policies have been implemented across geographic areas. METHODS Data from the 587 Silver Alerts activated in North Carolina in 2008, 2009, and 2010 were analyzed. Zero-inflated negative binomial regression and exploratory spatial analyses were employed. RESULTS Despite a policy focus on older adults and individuals with cognitive impairment, activation of Silver Alerts in a county was not related to the proportion of the population 65 years of age or older or to the prevalence of poor mental health in the county. Rather, a 1-unit increase in the proportion of the population comprised of African Americans increased the rate of Silver Alert activation by a factor of 1.019 (P < 0.01). Additionally, spatial analyses suggested that the number of Silver Alerts in a county was related to its proximity to North Carolina's state capital, Raleigh. LIMITATIONS These results should be interpreted with caution because an exploratory analytic approach was employed in both regression and spatial analyses. CONCLUSION The current mission and implementation of the Silver Alert program should be reviewed, given that significant effects were observed for the proportion of African Americans in a county and the county's distance from the state capital, but not for the proportion of older adults in the county or for the prevalence of impaired mental status.

The geographical distribution of schizophrenia was previously shown to correlate with the global distribution of tick-borne flaviviruses. The correlation suggests a natural resistance gene to flaviviruses could be involved in schizophrenia. The flavivirus resistance gene, Flv, a gene found in wild mice and certain in-bred strains, confers resistance to flaviviruses through the interaction of cellular proteins with the flaviviral 3' untranslated regions (UTRs). Although the sequence and product of Flv are unknown, translation elongation factor alpha-1 (EF-1) is a protein known to interact with the 3' UTR flavivirus RNA, forming some complexes with long half-lives that inhibit RNA growth. A study was performed to assess the homology between flaviviral UTRs, subunits of EF-1, and selected proteins reported as abnormal in schizophrenia. The UTRs of four flaviviruses with wide geographical and phylogenic distribution were manually translated. Using the National Biomedical Research Foundation protein databank, the amino acid sequences were correlated with the amino acid sequences of selected proteins. The amino acid sequences of the EF-1 subunits were then correlated with the same proteins. Similar amino acid correlations between the proteins, EF-1 subunits and viral UTRs suggest that translational pathophysiology resulting from the product of Flv can be postulated as the cause of protein abnormalities observed in schizophrenia.

This study evaluated the postoperative free-flap monitoring frequency protocol used in a maxillofacial unit for patients receiving free-tissue transfer for reconstruction following orofacial cancer. All free-tissue transfers undertaken in the unit between January 1992 and October 1998 were reviewed retrospectively. Of the 370 patients evaluated, 46 returned to theatre with compromised free flaps. The compromise was purely venous in origin in 37 of these cases, arterial in three and due to a combination of arterial and venous problems in six. Thirty-five of the flaps were successfully salvaged. On average, the clinical manifestation of the problem occurred 25.5 hours postoperatively. However, there was a significant time difference between flaps that were salvaged successfully and those that were not: in the salvaged group the compromise was identified 17.5 hours postsurgery compared with 51 hours for the unsuccessful group. The timing of the return to theatre following the identification of the compromise was a significant factor in the success rate: 71 minutes for those salvaged and 103 minutes for those not salvaged. It is recommended that flaps are monitored hourly for the first 72 postoperative hours and observations recorded on a chart.

OBJECTIVE - To determine the prevalence and risk factors for urinary incontinence among different racial/ethnic groups of overweight and obese women with type 2 diabetes. RESEARCH DESIGN AND METHODS - Cross-sectional analysis of baseline data from the Action for Health in Diabetes (Look AHEAD) study, a randomized clinical trial with 2,994 overweight/obese women with type 2 diabetes. RESULTS - Weekly incontinence (27%) was reported more often than other diabetes-associated complications, including retinopathy (7.5%), microalbuminuria (2.2%), and neuropathy (1.5%). The prevalence of weekly incontinence was highest among non-Hispanic whites (32%) and lowest among African Americans (18%), and Asians (12%) (P < 0.001). Asian and African American women had lower odds of weekly incontinence compared with non-Hispanic whites (75 and 55% lower, respectively; P < 0.001). Women with a BMI of ≥35 kg/m2had a higher odds of overall and stress incontinence (55-85% higher; P < 0.03) compared with that for nonobese women. Risk factors for overall incontinence, as well as for stress and urgency incontinence, included prior hysterectomy (40-80% increased risk; P < 0.01) and urinary tract infection in the prior year (55-90% increased risk; P < 0.001). CONCLUSIONS - Among overweight and obese women with type 2 diabetes, urinary incontinence is highly prevalent and far exceeds the prevalence of other diabetes complications. Racial/ethnic differences in incontinence prevalence are similar to those in women without diabetes, affecting non-Hispanic whites more than Asians and African Americans. Increasing obesity (BMI ≥35 kg/m2) was the strongest modifiable risk factor for overall incontinence and stress incontinence in this diverse cohort. © 2009 by the American Diabetes Association.