The Millennium Galaxy Catalogue: The MbhM_{bh}--LspheroidL_{spheroid} derived supermassive black hole mass function

Supermassive black hole mass estimates are derived for 1743 galaxies from the Millennium Galaxy Catalogue using the recently revised empirical relation between supermassive black hole mass and the luminosity of the host spheroid. The MGC spheroid luminosities are based on $R^{1/n}$-bulge plus exponential-disc decompositions. The majority of black hole masses reside between $10^6 M_{\odot}$ and an upper limit of $2\times10^9 M_{\odot}$. Using previously determined space density weights, we derive the SMBH mass function which we fit with a Schechter-like function. Integrating the black hole mass function over $10^6< M_{bh}/ M_{\odot} < 10^{10}$ gives a supermassive black hole mass density of ($3.8 \pm 0.6) \times 10^5 h^{3}_{70} M_{\odot}$ Mpc$^{-3}$ for early-type galaxies and ($0.96 \pm 0.2) \times10^5 h^{3}_{70} M_{\odot}$ Mpc$^{-3}$ for late-type galaxies. The errors are estimated from Monte Carlo simulations which include the uncertainties in the $M_{bh}$--$L$ relation, the luminosity of the host spheroid and the intrinsic scatter of the $M_{bh}$--$L$ relation. Assuming supermassive black holes form via baryonic accretion we find that ($0.008\pm0.002) h_{70}^{3}$ per cent of the Universe's baryons are currently locked up in supermassive black holes. This result is consistent with our previous estimate based on the $M_{bh}$--$n$ (S{\'e}rsic index) relation.Comment: 10 pages, 6 figures, accepted to MNRA

Perfecţionarea metodei combinate de tratament al tumorilor capului şi gâtului cu aplicarea factorilor fizici în scopul îmbunătăţirii procesului de reabilitare a bolnavilor oncologici

În ultimii ani tumorile regiunii capului şi gâtului în structura morbidităţii prin cancer s-au plasat pe primul loc, bolnavii primari înregistraţi anual alcătuind circa 1300, ceea ce constituie circa 30,0% ̊ ̊ ̊.Pe parcursul a 5 ani, metoda combinată de tratament cu utilizarea factorilor fizici a fost aplicată la 472 de pacienţi: 1. Ca al pielii regiunii capului şi gâtului (carcinom paviemntos) – 27 de bolnavi. 2. Ca bazocelular al pielii regiunii capului şi gâtului – 59 de bolnavi. 3. Ca al buzei inferioare – 160 de bolnavi. 4. Ca al mucoasei cavităţii bucale – 52 de bolnavi. 5. Ca al laringelui – 174 de bolnavi. Bolnavii au fost selectaţi prin metoda rondomizată în policlinica Institutului Oncologic din Moldova. Metoda combinată de tratament aplicată de noi a constat în efectuarea tratamentului tradiţional chirurgical în asociere cu: - radioterapie perioperatorie la aparatul „Rocus”; - criodistrucţie cu aparatul „KP – 02”; - hipertermie la aparatul „Volna 2”; - lazeroterapie la aparatul „УЛФ – 01”. Aplicarea metodei propuse de tratament a permis îmbunătăţirea rezultatelor nemijlocite cu 15%. Tratamentul complex al acestor bolnavi a inclus şi un şir de măsuri de reabilitare medicală, dintre care cea mai importantă a fost plastia defectelor posttumorale cu diverse lambouri pediculate (cervicale,humerale, deltopectorale, tocarodorsale), libere, combinate şi lambouri microchirurgicale

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Adaptation of Venezuelan refugees in Colombia: the mediating roles of acculturation orientations in influencing acculturation adaptations

As of 2021, over 5.4 million Venezuelans have fled their home country in search of safety, food, medicine and access to essential services. This is the most substantial exodus in the recent history of Latin America. Colombia has received 2 million of these refugees, making it the nation host to the greatest number of Venezuelan refugees. The present research aims to examine the relations between the sociocultural and psychological factors that are associated with Psychological Adaptation of Venezuelan refugees living in Colombia. We also examined how these relations were mediated by the acculturation orientations. Among Venezuelan refugees, higher Psychological Strength, lower Perceived Discrimination, higher National Identity and higher Outgroup Social Support, were significantly associated with higher engagement with Colombian society and better Psychological Adaptation. Orientation to the host (Colombian) society mediated the association between (a) National Identity and Psychological Adaptation, (b) Outgroup Social Support and Psychological Adaptation and (c) Perceived Discrimination and Psychological Adaptation. The results may inform refugee receiving societies of some essential factors and positive strategies behind adaptation of refugees

Real-world evaluation of rapid and laboratory-free COVID-19 triage for emergency care: external validation and pilot deployment of artificial intelligence driven screening.

BACKGROUND Uncertainty in patients' COVID-19 status contributes to treatment delays, nosocomial transmission, and operational pressures in hospitals. However, the typical turnaround time for laboratory PCR remains 12-24 h and lateral flow devices (LFDs) have limited sensitivity. Previously, we have shown that artificial intelligence-driven triage (CURIAL-1.0) can provide rapid COVID-19 screening using clinical data routinely available within 1 h of arrival to hospital. Here, we aimed to improve the time from arrival to the emergency department to the availability of a result, do external and prospective validation, and deploy a novel laboratory-free screening tool in a UK emergency department. METHODS We optimised our previous model, removing less informative predictors to improve generalisability and speed, developing the CURIAL-Lab model with vital signs and readily available blood tests (full blood count [FBC]; urea, creatinine, and electrolytes; liver function tests; and C-reactive protein) and the CURIAL-Rapide model with vital signs and FBC alone. Models were validated externally for emergency admissions to University Hospitals Birmingham, Bedfordshire Hospitals, and Portsmouth Hospitals University National Health Service (NHS) trusts, and prospectively at Oxford University Hospitals, by comparison with PCR testing. Next, we compared model performance directly against LFDs and evaluated a combined pathway that triaged patients who had either a positive CURIAL model result or a positive LFD to a COVID-19-suspected clinical area. Lastly, we deployed CURIAL-Rapide alongside an approved point-of-care FBC analyser to provide laboratory-free COVID-19 screening at the John Radcliffe Hospital (Oxford, UK). Our primary improvement outcome was time-to-result, and our performance measures were sensitivity, specificity, positive and negative predictive values, and area under receiver operating characteristic curve (AUROC). FINDINGS 72 223 patients met eligibility criteria across the four validating hospital groups, in a total validation period spanning Dec 1, 2019, to March 31, 2021. CURIAL-Lab and CURIAL-Rapide performed consistently across trusts (AUROC range 0·858-0·881, 95% CI 0·838-0·912, for CURIAL-Lab and 0·836-0·854, 0·814-0·889, for CURIAL-Rapide), achieving highest sensitivity at Portsmouth Hospitals (84·1%, Wilson's 95% CI 82·5-85·7, for CURIAL-Lab and 83·5%, 81·8-85·1, for CURIAL-Rapide) at specificities of 71·3% (70·9-71·8) for CURIAL-Lab and 63·6% (63·1-64·1) for CURIAL-Rapide. When combined with LFDs, model predictions improved triage sensitivity from 56·9% (51·7-62·0) for LFDs alone to 85·6% with CURIAL-Lab (81·6-88·9; AUROC 0·925) and 88·2% with CURIAL-Rapide (84·4-91·1; AUROC 0·919), thereby reducing missed COVID-19 cases by 65% with CURIAL-Lab and 72% with CURIAL-Rapide. For the prospective deployment of CURIAL-Rapide, 520 patients were enrolled for point-of-care FBC analysis between Feb 18 and May 10, 2021, of whom 436 received confirmatory PCR testing and ten (2·3%) tested positive. Median time from arrival to a CURIAL-Rapide result was 45 min (IQR 32-64), 16 min (26·3%) sooner than with LFDs (61 min, 37-99; log-rank p<0·0001), and 6 h 52 min (90·2%) sooner than with PCR (7 h 37 min, 6 h 5 min to 15 h 39 min; p<0·0001). Classification performance was high, with sensitivity of 87·5% (95% CI 52·9-97·8), specificity of 85·4% (81·3-88·7), and negative predictive value of 99·7% (98·2-99·9). CURIAL-Rapide correctly excluded infection for 31 (58·5%) of 53 patients who were triaged by a physician to a COVID-19-suspected area but went on to test negative by PCR. INTERPRETATION Our findings show the generalisability, performance, and real-world operational benefits of artificial intelligence-driven screening for COVID-19 over standard-of-care in emergency departments. CURIAL-Rapide provided rapid, laboratory-free screening when used with near-patient FBC analysis, and was able to reduce the number of patients who tested negative for COVID-19 but were triaged to COVID-19-suspected areas. FUNDING The Wellcome Trust, University of Oxford Medical and Life Sciences Translational Fund

COVID-19 admission risk tools should include multiethnic age structures, multimorbidity and deprivation metrics for air pollution, household overcrowding, housing quality and adult skills.

BACKGROUND Ethnic minorities account for 34% of critically ill patients with COVID-19 despite constituting 14% of the UK population. Internationally, researchers have called for studies to understand deterioration risk factors to inform clinical risk tool development. METHODS Multicentre cohort study of hospitalised patients with COVID-19 (n=3671) exploring determinants of health, including Index of Multiple Deprivation (IMD) subdomains, as risk factors for presentation, deterioration and mortality by ethnicity. Receiver operator characteristics were plotted for CURB65 and ISARIC4C by ethnicity and area under the curve (AUC) calculated. RESULTS Ethnic minorities were hospitalised with higher Charlson Comorbidity Scores than age, sex and deprivation matched controls and from the most deprived quintile of at least one IMD subdomain: indoor living environment (LE), outdoor LE, adult skills, wider barriers to housing and services. Admission from the most deprived quintile of these deprivation forms was associated with multilobar pneumonia on presentation and ICU admission. AUC did not exceed 0.7 for CURB65 or ISARIC4C among any ethnicity except ISARIC4C among Indian patients (0.83, 95% CI 0.73 to 0.93). Ethnic minorities presenting with pneumonia and low CURB65 (0-1) had higher mortality than White patients (22.6% vs 9.4%; p<0.001); Africans were at highest risk (38.5%; p=0.006), followed by Caribbean (26.7%; p=0.008), Indian (23.1%; p=0.007) and Pakistani (21.2%; p=0.004). CONCLUSIONS Ethnic minorities exhibit higher multimorbidity despite younger age structures and disproportionate exposure to unscored risk factors including obesity and deprivation. Household overcrowding, air pollution, housing quality and adult skills deprivation are associated with multilobar pneumonia on presentation and ICU admission which are mortality risk factors. Risk tools need to reflect risks predominantly affecting ethnic minorities

Characterisation and outcomes of ARDS secondary to pneumonia in patients with and without SARS-CoV-2: a single-centre experience.

INTRODUCTION Acute respiratory distress syndrome (ARDS) is the major cause of mortality in patients with SARS-CoV-2 pneumonia. It appears that development of 'cytokine storm' in patients with SARS-CoV-2 pneumonia precipitates progression to ARDS. However, severity scores on admission do not predict severity or mortality in patients with SARS-CoV-2 pneumonia. Our objective was to determine whether patients with SARS-CoV-2 ARDS are clinically distinct, therefore requiring alternative management strategies, compared with other patients with ARDS. We report a single-centre retrospective study comparing the characteristics and outcomes of patients with ARDS with and without SARS-CoV-2. METHODS Two intensive care unit (ICU) cohorts of patients at the Queen Elizabeth Hospital Birmingham were analysed: SARS-CoV-2 patients admitted between 11 March and 21 April 2020 and all patients with community-acquired pneumonia (CAP) from bacterial or viral infection who developed ARDS between 1 January 2017 and 1 November 2019. All data were routinely collected on the hospital's electronic patient records. RESULTS A greater proportion of SARS-CoV-2 patients were from an Asian ethnic group (p=0.002). SARS-CoV-2 patients had lower circulating leucocytes, neutrophils and monocytes (p<0.0001), but higher CRP (p=0.016) on ICU admission. SARS-CoV-2 patients required a longer duration of mechanical ventilation (p=0.01), but had lower vasopressor requirements (p=0.016). DISCUSSION The clinical syndromes and respiratory mechanics of SARS-CoV-2 and CAP-ARDS are broadly similar. However, SARS-CoV-2 patients initially have a lower requirement for vasopressor support, fewer circulating leukocytes and require prolonged ventilation support. Further studies are required to determine whether the dysregulated inflammation observed in SARS-CoV-2 ARDS may contribute to the increased duration of respiratory failure

Utility of severity assessment tools in COVID-19 pneumonia: a multicentre observational study.

BACKGROUND Severity scores in pneumonia and sepsis are being applied to SARS-CoV-2 infection. We aimed to assess whether these severity scores are accurate predictors of early adverse outcomes in COVID-19. METHODS We conducted a multicentre observational study of hospitalised SARS-CoV-2 infection. We assessed risk scores (CURB65, qSOFA, Lac-CURB65, MuLBSTA and NEWS2) in relation to admission to intensive care or death within 7 days of admission, defined as early severe adverse events (ESAE). The 4C Mortality Score was also assessed in a sub-cohort of patients. FINDINGS In 2,387 participants, the overall mortality was 18%. In all scores examined, increasing score was associated with increased risk of ESAE. Area under the curve (AUC) to predict ESAE for CURB65, qSOFA, Lac-CURB65, MuLBSTA and NEWS2 were 0.61, 0.62, 0.59, 0.59 and 0.68, respectively. AUC to predict ESAE was 0.60 with ISARIC 4C Mortality Score. CONCLUSION None of the scores examined accurately predicted ESAE in SARS-CoV-2 infection. Non-validated scores should not be used to inform clinical decision making in COVID-19