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It is estimated that by 2040, Chronic Kidney Disease (CKD) will be the 5th main cause of global deaths. It has been suggested that hyperphosphatemia is among the main factors leading to the increased risk of death. This review focuses on potential and currently used Phosphate Binders (PB). Aluminum hydroxide is presently not recommended due to potential aluminum toxicity. Calciumcontaining phosphate binders (CCPB) can cause calcium overload, resulting in hypercalcemia and an increased risk of cardiovascular diseases. Magnesium and calcium complexes were suggested to be as effective as sevelamer in the reduction of serum phosphate, with the potential to slow down the process of calcification. However, limited studies have been conducted in this area. Although sevelamer seemed to have a positive influence on cardiovascular calcification and arterial stiffness, its influence on mortality was unclear. Sevelamer crystal accumulation in the Gastrointestinal tract (GI) can cause gastrointestinal bleeding. Lanthanum carbonate seemed to lower all-cause mortality and reduce the chance of hypercalcemia, even though a deposit in the GI tract was observed. Colestilan, like sevelamer, reduced LDL cholesterol. Sucroferric oxyhydroxide had a lower pill burden than other PBs and it seemed to reduce serum FGF-23. Ferric citrate improved parameters that are related to anemia but can cause iron overload. Bixalomer appeared to have fewer gastrointestinal side effects than sevelamer. Nano-lanthanum hydroxide and SBR759 may have an interesting future as PBs. In conclusion, the development of new PBs should also take into consideration their potential to function as protection modifiers.

Cel pracySyntetyczne katynony (znane również jako "sole do kąpieli") to nowe substancje psychoaktywne wprowadzone na rynek globalny w ciągu ostatnich 10 lat jako zamienniki nielegalnej amfetaminy. Ze względu na łatwą dostępność szybko stały się popularne. Celem pracy było określenie związku stosowania syntetycznych katynonów z objawami depresyjnymi i zachowaniami ustnymi wśród użytkowników rekreacyjnych.MetodaUżytkownicy forów internetowych związanych z narkotykami zostali poproszeni o wypełnienie ankiety za pośrednictwem platformy Google Forms. Kwestionariusz zawierał pytania dotyczące schematów używania środków psychoaktywnych, Inwentarz Depresji Becka II (BDI II) oraz Kwestionariusz Zachowań Ustnych (OBC) oraz podstawowe dane demograficzne (wiek, płeć).Wyniki150 uczestników (75 w grupie badanej, 75 w grupie kontrolnej) wzięło udział w badaniu. W grupie badanej (w wieku od 15 do 28 lat) wszyscy uczestnicy korzystali z katynonów i innych substancji psychoaktywnych. 42 respondentów korzystało z katynonów w ciągu ostatniego miesiąca. Analiza statystyczna wykazała korelację między liczbą zażywanych substancji psychoaktywnych i poziomem depresji w obu grupach (badanej i kontrolnej), a także statystycznie istotnie wyższą średnią wartościąwyników OBC w grupie użytkowników katynonów w porównaniu z grupą kontrolną. Korelacja między depresją a OBC była statystycznie istotna zarówno dla grupy badanej, jak i kontrolnej.WnioskiBiorąc pod uwagę łatwy dostęp do syntetycznych katynonów, częste zatrucia i młody wiek użytkowników tego badania, temat powinien zostać szerzej przebadany. Substancje psychoaktywne mogą predysponować do rozwoju depresji i różnych form parafunkcyjnych zachowań ustnych.

Objective To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study. Methods Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score. Results TST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers. Conclusions TST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients. Significance This multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients.

Background: Data on HIV-1 controllers in Africa are scarce. We report the proportion of HIV-1 controllers in a group of adults prospectively monitored with frequent viral load measurements as part of a clinical trial in West Africa. Methods: For the Temprano trial, antiretroviral therapy (ART)-naive HIV-1 infected adults with no criteria for starting ART were randomized to start ART immediately or defer ART until the WHO starting criteria were met. Plasma viral load was measured every 6 months. The trial follow-up was 30 months. We considered all Temprano participants randomized to defer ART. Patients with all semestrial viral

Evolutionary-based predictions imply that the premenstrual syndrome (PMS) affects women who failed to conceive while in biosocial conditions that allow immediate reproduction. We investigated how the PMS is related to the heart rate variability (HRV), a marker of general fitness and well-being. The HRV indices (SDNN and rMSSD) were calculated using resting ECGs of 113 physiologically fertile women and 64 women using hormonal contraception (HC users, HCu). The intensity of PMS symptoms was self-assessed (Shortened Premenstrual Assessment Form). Analyses were conducted using parametric and nonparametric tests and general linear modelling (GLM). In HC non-users (HCnu), a greater intensity of PMS symptoms was significantly associated with higher values of HRV. Similar relations were not present in HCu. Post-hoc GLM confirmed that the relation between the PMS intensity and HRV indices varies as a function of the HCu status. A positive association between the PMS intensity and high HRV indices in women who did not use HC may confirm that the PMS affects fertile women who did not conceive, despite being in conditions favorable to pregnancy. The absence of a similar link in HCu women implies that synthetic steroids may disturb the link between the PMS and functioning of the autonomic nervous system.

We studied a sample of 146 Polish, exclusively breastfeeding mothers and their healthy born on time infants to explore the effect of perinatal psychosocial stress on breast milk composition. Maternal perinatal stress was assessed using Recent Life Changes Questionnaire summarizing stressful events from the previous six months. Stress reactivity was determined by administering the cold pressor test and measuring cortisol in saliva samples taken during the test. Breast milk sample was taken to measure energy, protein, fat, lactose, and fatty acid content. Analyses revealed that stress reactivity was positively associated with milk fat and long-chain unsaturated fatty acids and negatively associated with milk lactose. Perinatal psychosocial stress negatively affected energy density, fat as well as medium-chain and long-chain saturated fatty acids in milk. These results, together with previous studies, advocate monitoring maternal psychological status during the peripartum to promote breastfeeding and healthy infant nutrition.

The dramatically changing situation during COVID-19 pandemic, is anticipated to provoke psycho-emotional disturbances and somatization arising from the current epidemiological situation that will become a significant problem for global and regional healthcare systems. The aim of this study was to identify the predictors, risk factors and factors associated with mental disorders, headache and potentially stress-modulated parafunctional oral behaviors among the adult residents of North America and Europe as indirect health effects of the COVID-19 pandemic. This may help limit the long-term effects of this and future global pandemic crises. The data were collected from 1642 respondents using an online survey. The results demonstrated increased levels of anxiety, depression, headache and parafunctional oral behaviors during the COVID-19 pandemic in both North American and European residents. The results of this study facilitated the definition of the group most predicted to experience the aforementioned secondary effects of the pandemic. This group included females younger than 28.5 years old, especially those who were single, less well educated and living in Europe. In case of this and other global crises this will allow faster defining the most vulnerable groups and providing rapid and more targeted intervention.

BACKGROUND: It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir-based anti-retroviral therapy (ART). METHODS: Using data collected between 2008– 2015, we studied people with HIV in sub-Saharan Africa initiating immediate ART in the Temprano randomized control trial. We classified participants into HBV groups at ART-initiation: hepatitis B surface antigen (HBsAg)-positive with HBV DNA ≥2000 IU/mL; HBsAg-positive with HBV DNA

Background Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4+ cell counts in this association is poorly defined. We aimed to determine whether HIV–HBV co-infection influences changes in CD4+ cell count before and during antiretroviral therapy and whether it affects mortality risk at levels of CD4+. Methods 2052 HIV-positive participants from Côte d’Ivoire in a randomized-control trial assessing early or deferred ART were included. HBV-status was determined by hepatitis B surface antigen (HBsAg). Changes in CD4+ cell levels were estimated using a mixed-effect linear model. The incidence rates of all-cause mortality were estimated at CD4+ counts ≤350, 351–500, >500/mm3 and were compared between HBV-status groups as incidence rate ratios (IRR). Results At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA + decline before ART initiation and no differences in CD4+ increase after ART initiation. After adjusting for sex, age, baseline HIV RNA level, and early/deferred ART arm, mortality rates were not significantly different between HBsAg-positive versus HBsAg-negative participants across strata of CD4+ levels. However, HBsAg-positive individuals with HBV-DNA ≥2000 IU/mL versus HBsAg-negative individuals had increased mortality rates at ≤350/mm3 (adjusted-IRR = 3.82, 95% CI = 1.11–9.70) and 351–500/mm3 (adjusted-IRR = 4.37, 95% CI = 0.98–13.02), but not >500/mm3 (adjusted-IRR = 1.07, 95% CI = 0.01–4.91). Conclusion Despite no effect of HBV-infection on CD4+ levels, HIV-HBV co-infected individuals with high HBV replication are at higher risk of mortality when CD4+ is 3.

Suicide is very common among people with mental disorders. In addition, suicide mortality rates are stable in this group, while they are decreasing in the general population. The vital statuses of adult inpatients admitted to French psychiatry departments in 2008–2009 were researched in death databases on 31 December 2013. Suicide probability was calculated using a Kaplan–Meier analysis, and standardized mortality ratios (SMRs) were calculated in relation to the population of the study area. Among the 13,979 patients included in the study, (7416 men and 6563 women; mean age 43.6 ± 14.6 years), 1454 died in total, among whom 286 died by suicide an average of 4.9 years after the date of their enrolment. The cumulative probability of suicide was 0.8% at 1 year, 1.3% at 2 years and 2.5% at 6 years. The SMR value, which was 1492 for the whole group of patients and was twice as high in women (2494) as in men (1220), decreased with age (from 2078 in patients aged 18–34 years to 1278 in patients aged 75 years or more). Our study confirms that suicide mortality is higher in inpatients admitted to French psychiatry units than in the general population and advocates specific prevention programmes for this group.

Sleep bruxism (SB) and obstructive sleep apnea (OSA) are co-occurring sleep conditions. The study aimed to evaluate the association of selected single-nucleotide polymorphisms (SNPs) occurring within the genes of the serotonin and dopamine pathways in SB and OSA and investigate the relationship between them. The study group included 100 Caucasian patients. SB and OSA were diagnosed in 74 and 28 patients, respectively. In addition, 125 unrelated Caucasian healthy blood donors served as randomly selected controls to enable comparison of polymorphisms. The following SNPs were analyzed: rs2770304 and rs6313 within the serotonin receptor encoding gene (HTR2A), rs4680 polymorphism of the catechol-O-methyltransferase (COMT) gene, and rs686 within the dopamine receptor (DRD1) encoding gene. The prevalence of the DRD1 rs686 G variant (GG homozygosity) was found to be high in the study group compared to the control group. Bruxism episode index (BEI) was found to be significantly increased in the HTR2A rs6313 TT homozygotes compared to the heterozygous patients. Moreover, within a group of the HTR2A rs2770304 TT homozygous cases, a statistically significant correlation was observed between BEI and apnea–hypopnea index. These results indicate that DRD1 rs686 may potentially affect predisposition to SB, that HTR2A rs6313 SNP may be involved in SB pathogenesis, and that HTR2A rs2770304 polymorphism might contribute to the association between SB and OSA. This suggests a possible genetic contribution to the etiology of primary SB.

Objective To determine the risk factors associated with radiographic changes and clinical outcomes following 3-level anterior cervical discectomy and fusion (ACDF) using rigidplate constructs and cortico-cancellous allograft. ACDF has demonstrated efficacy for treatment of multilevel degenerative cervical conditions, but current data exists in small heterogeneous forms. Methods A retrospective review included 98 patients with primary 3-level ACDF surgery at one institution from 2008 to 2013 with minimum 1-year follow-up. Cervical sagittal vertical axis (SVA), segmental height, fusion, and lordosis radiographs were measured preoperatively and at 2 postoperative periods. Results Rates of asymptomatic pseudarthroses and total reoperations were 18% and 4%, respectively. Results demonstrated immediate improvements in cervical lordosis (5.5°, p < 0.01) and segmental height (5.0-mm increase, p < 0.01) with little changes in the cervical SVA (3.2-mm increase, p < 0.01). The segmental height decreased from immediate postoperative period to final follow-up (1.7-mm decrease, p < 0.01). Older age was protective against radiolucent lines (p < 0.05). Patient-reported outcomes significantly improved following surgery (p < 0.01). Current smoking status and diagnosis of diabetes mellitus had no impact on radiographic or clinical outcomes. Risk factors were not identified for the 5 reoperations (4%). Conclusion Three-level ACDF with rigid-plating and cortico-cancellous allograft is an effective procedure for degenerative diseases of the cervical spine without the application of additional adjuncts or combined anteriorposterior cervical surgeries. Significant improvements in cervical lordosis, segmental height, and segmental alignment can be achieved with little change in cervical SVA and a low rate of reoperations over short-term follow-up. Similarly, patient-reported outcomes show significant improvements.

Quantum computing is set to revolutionize the world of software engineering. Currently, quantum paradigms and languages are being developed that are bringing the physical principles of quantum information closer to solving problems in multiple application domains. These paradigms and languages will continue to evolve and bring quantum computing closer to software engineering, and to an increasingly massive use of it. Unfortunately, as quantum software engineering advances in bringing these new capabilities closer to widespread industry exploitation, attackers will turn the spotlight on quantum software vulnerabilities, on what will be the new battlefront in the world of cybersecurity. In this paper, we approach this security from scratch, starting with an introduction to the current state of quantum programming languages. Then, some current hardware limitations are presented and how these affect quantum software engineering. Followed, we make an overview on the analysis of the quantum languages in terms of security together with some of the research made up to date. As a conclusion, we express the necessity to avoid the many times made mistake of not including security considerations from the first steps in the design of computing paradigms. An error that is repeated a second time is not an error; it is, indeed, a choice.

The dramatically changing situation during COVID-19 pandemic, is anticipated to provoke psycho-emotional disturbances and somatization arising from the current epidemiological situation that will become a significant problem for global and regional healthcare systems. The aim of this study was to identify the predictors, risk factors and factors associated with mental disorders, headache and potentially stress-modulated parafunctional oral behaviors among the adult residents of North America and Europe as indirect health effects of the COVID-19 pandemic. This may help limit the long-term effects of this and future global pandemic crises. The data were collected from 1642 respondents using an online survey. The results demonstrated increased levels of anxiety, depression, headache and parafunctional oral behaviors during the COVID-19 pandemic in both North American and European residents. The results of this study facilitated the definition of the group most predicted to experience the aforementioned secondary effects of the pandemic. This group included females younger than 28.5 years old, especially those who were single, less well educated and living in Europe. In case of this and other global crises this will allow faster defining the most vulnerable groups and providing rapid and more targeted intervention.

International audience; Introduction: HIV Testing and Counselling (HTC) remains a key challenge in achieving control of the HIV epidemic by 2030. In the early 2010s, the President's Emergency Plan for AIDS Relief (Pepfar) adopted targeted HTC strategies for populations and geographical areas most affected by HIV. We examine how Pepfar defined targeted HTC in Côte d'Ivoire, a country with a mixed HIV epidemic, after a decade of expanding HTC services. Methods: We explored the evolution of HTC strategies through the Country Operational Plans (COP) of Pepfar during its phase 3.0, from COP 14 to COP 17 (October 2014 to September 2018) in Côte d'Ivoire. We conducted an analysis of the grey literature over the period 2014 to 2018 (Budget & Target Report, Strategic Direction Summary, Sustainability Index and Dashboard Summary, https://data.pepfar.gov). We also conducted a qualitative study in Côte d'Ivoire (2015 to 2018) using indepth interviews with stakeholders in the AIDS public response: CDC/Pepfar (3), Ministry of Health (3), intermediary NGOs (7); and public meeting observations (14). Results: Since the COP 14, Pepfar's HIV testing strategies have been characterized by significant variations in terms of numerical, geographical and population targets. While the aim of COP 14 and COP 15 seemed to be the improvement of testing efficacy in general and testing yield in particular, COP 16 and COP 17 prioritized accelerating progress towards the "first 90" (i.e. reducing the proportion of people living with HIV who are unaware of their HIV). A shift was observed in the definition of testing targets, with less focus on the inclusion of programmatic data and feedback from field actors, and greater emphasis on the use of models to estimate and disaggregate the targets by geographical units and sub-populations (even if the availability of data by this disaggregation was limited or uncertain); increasingly leading to gaps between targets and results. Conclusions: These trials and tribulations question the real and long-term effectiveness of annually-revised, fragmented strategies, which widen an increasing disparity between the realities of the actors on the ground and the objectives set in Washington.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here, we report that patients with EGPA have elevated levels of TSLP, IL-25, and soluble ST2, which are well-characterized cytokine "alarmins" that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. To explore the mechanism of these findings in patients, we established a model of EGPA in which active vasculitis and pulmonary hemorrhage were induced by IL-33 administration in predisposed, hypereosinophilic mice. In this model, induction of pulmonary hemorrhage and vasculitis was dependent on ILC2s and signaling through IL4Rα. In the absence of IL4Rα or STAT6, IL-33-treated mice had less vascular leak and pulmonary edema, less endothelial activation, and reduced eotaxin production, cumulatively leading to a reduction of pathologic eosinophil migration into the lung parenchyma. These results offer a mouse model for use in future mechanistic studies of EGPA, and they suggest that IL-33, ILC2s, and IL4Rα signaling may be potential targets for further study and therapeutic targeting in patients with EGPA.

BACKGROUND AND PURPOSE: In patients with pulmonary hypertension (PH) associated with lung disease and/or hypoxia (Group III), decreased pulmonary vascular tone and tissue hypoxia is therapeutically beneficial. PGE(2) and PGI(2) induce potent relaxation of human bronchi from non‐PH (control) patients via EP(4) and IP receptors, respectively. However, the effects of PGE(2)/PGI(2) and their mimetics on human bronchi from PH patients are unknown. Here, we have compared relaxant effects of several PGI(2)–mimetics approved for treating PH Group I with several PGE(2)–mimetics, in bronchial preparations derived from PH Group III and control patients. EXPERIMENTAL APPROACH: Relaxation of bronchial muscle was assessed in samples isolated from control and PH Group III patients. Expression of prostanoid receptors was analysed by western blot and real‐time PCR, and endogenous PGE(2), PGI(2), and cAMP levels were determined by ELISA. KEY RESULTS: Maximal relaxations induced by different EP(4) receptor agonists (PGE(2), L‐902688, and ONO‐AE1‐329) were decreased in human bronchi from PH patients, compared with controls. However, maximal relaxations produced by PGI(2)–mimetics (iloprost, treprostinil, and beraprost) were similar for both groups of patients. Both EP(4) and IP receptor protein and mRNA expressions were significantly lower in human bronchi from PH patients. cAMP levels significantly correlated with PGI(2) but not with PGE(2) levels. CONCLUSION AND IMPLICATIONS: The PGI(2)–mimetics retained maximal bronchodilation in PH Group III patients, whereas bronchodilation induced by EP(4) receptor agonists was decreased. Restoration of EP(4) receptor expression in airways of PH Group III patients with respiratory diseases could bring additional therapeutic benefit.

CERVOXY CLIN; International audience; Background - Anticancer immune responses are negatively regulated by programmed cell death 1 (PD-1) T-cell membrane protein interaction with its ligand, programmed death ligand 1 (PD-L1), on cancer cells. We sought to assess the prognostic role of PD-L1 expression in tumor samples from patients enrolled onto the IFCT-0701 MAPS randomized phase 3 trial (NCT00651456). Patients and methods - Tumor samples were analyzed by immunohistochemistry for percentages of PD-L1 membrane-stained tumor cells using the E1L3N clone, and data were correlated to survival by multivariate Cox models including stratification variables. Results - PD-L1 staining was assessed in 214 (47.75%) of 448 patients. Epithelioid subtype represented 83.7% (179/214). Absence of PD-L1 staining occurred in 137 (64.1%) of 214 malignant pleural mesothelioma (MPM) samples, while 77 (35.9%) of 214 were PD-L1 positive, with 50 (64.9%) of 77 showing < 50% PD-L1-expressing tumor cells. Sarcomatoid/biphasic subtypes were more commonly PD-L1 positive than epithelioid subtype (P < .001). In patients with 1% or more PD-L1-stained tumor cells, median overall survival (OS) was 12.3 months versus 22.2 months for other patients (hazard ratio [HR] = 1.25; 95% confidence interval [CI], 0.93-1.67; P = .14). OS did not differ according to PD-L1 positivity in multivariate analyses (adjusted HR = 1.10; 95% CI, 0.81-1.49; P = .55). With a 50% cutoff, PD-L1-positive patients displayed a 10.5 months median OS versus 19.3 months for patients with lower PD-L1 expression (HR = 1.93; 95% CI, 1.27-2.93; P = .002). OS did not significantly differ in adjusted Cox models (adjusted HR = 1.20; 95% CI, 0.74-1.94; P = .47). In the 179 epithelioid MPM patients, high PD-L1 staining (≥ 50% of tumor cells) negatively affected OS, although not significantly, showing a 12.3-month median OS (95% CI, 4.3-21.6) versus 23-month (95% CI, 18.5-25.2) for patients with tumor PD-L1 staining in < 50% cells (P = .071). The progression-free survival (PFS) differences were statistically significant, with a longer 9.9-month median PFS in patients with low PD-L1 staining (< 50% cells) compared to 6.7 months of median PFS in patients with high PD-L1 expression (≥ 50% cells) (P = .0047). Conclusion - Although high PD-L1 tumor cell expression was associated with poorer OS in MPM patients from the MAPS trial, its prognostic influence was lost in multivariate analyses in the whole cohort, while PD-L1 expression was strongly associated with the sarcomatoid/biphasic subtypes. In the epithelioid MPM subset of patients, high PD-L1 tumor expression (≥ 50%) negatively affected OS and PFS, with this prognostic influence remaining statistically significant for PFS after adjustment in multivariate Cox model.

The paper presents the possibility of using machine vision in the industrial area. The case study is oriented to indirect image processing in a robotic cell using a Matlab tool. Theoretical part of the contribution is devoted to the comparative analysis of various methods of the object detection and recognition. Analysis of the functionality, speed, performance and reliability of selected methods in the object detection and recognition area is processed. In the practical part, a method of implementing an indirect machine vision is designed to control the handling of objects detected and recognized on the basis of an operator requirement. Based on the analysis of the sample robotic workplace and the identified limitations, possibility of using the indirect computer vision is suggested. In such a case, the image of the workspace scene is saved on the storage and then processed by an external element. The processing result is further distributed in a defined form by a selected channel to the control component of the production cell.

To retrospectively characterize the molecular features of Non-Small Cell Lung Carcinomas (NSCLC) with peritoneal carcinomatosis (PC), clinicopathological data of 12 patients diagnosed with NSCLC and PC between 2007 and 2016 were collected. Immunohistochemistry and Next Generation Sequencing (NGS) were performed on cases with available material. PC was the initial presentation of NSCLC in 17% of the cases. Overall, patients with PC displayed a poor median survival of 12 weeks. Histology was adenocarcinoma in 11 cases. 37.5% of cases showed PD-L1 immunostaining positivity (50% cut-off). ALK and ROS1 immunostainings were negative. Using NGS, we identified 17 molecular alterations in 9 genes (TP53, KRAS, STK11, BRAF, EGFR, DDR2, ERBB4, SMAD4, CTNNB1) in 88.9% of adenocarcinomas. To the best of our knowledge, 5 of these variants are not referenced in the literature. In conclusion, PC might be the initial presentation of NSCLC. Molecular profiling of our cases did not find any effective targetable alteration, except from high PD-L1 expression.

This paper provides a design of the Information System architecture to support a connected construction site. In order to master the diversity and the complexity of construction site processes, theories are needed that separate the stable essence of the smart construction site from the variable way in which it is realized and implemented. For that, construction site processes were mapped before linking each data path with the existing technological tools using correspondence matrixes. The results enable the definition of a proper system able to deal with the resources allocated to the construction process functionalities. The main challenge faced in this research was to identify which pertinent data is needed that activates the resources to complete each given construction task.

AIMS Antibody-mediated rejection (AMR) is an emerging and challenging issue in transplantation. Endothelial deposition of C4d and microvascular inflammation (MI) are reliable markers of AMR in renal and cardiac transplantation, but remain controversial in the lung. Our aim was to assess C4d immunohistochemistry and histological patterns for the diagnosis of lung AMR. METHODS AND RESULTS We reviewed 158 transbronchial biopsies (TBBs) (n = 85 clinically indicated, and n = 73 surveillance TBBs) from 48 recipients, blinded to clinical and serological data. C4d was scored as 0, 1+ ( 50%). TBBs were reassessed for MI and acute lung injury (ALI). Donor-specific antibodies (DSAs), acute clinical graft dysfunction and chronic lung allograft graft dysfunction (CLAD) were recorded. C4d3+, C4d2+, C4d1+ and C4d0 occurred respectively in four (2.5%), six (3.8%), 28 (17.7%) and 120 (75.9%) TBBs. MI and ALI were rare but more frequent in C4d1-3+ TBBs than in the absence of C4d. C4d2+ was frequently observed with concomitant infection. Among the surveillance TBBs, only two (2.7%) showed MI. Neither ALI nor C4d3+ was diagnosed on surveillance TBBs. No significant association was found between histopathological findings and DSAs. All four patients with C4d3+ could retrospectively be diagnosed with AMR and developed CLAD. CONCLUSION Although rare, diffuse C4d deposition appears to be a strong indication of acute clinical AMR in lung transplant patients, whereas intermediate C4d2+ requires more investigations. In stable patients, histopathology and C4d may lack the sensitivity to diagnose subclinical AMR. This emphasises the need for a multidisciplinary evaluation of each suspected AMR case, and the need for complementary diagnostic tools.

This reflection on the influence of Napoleon and the consequences of the wars on the major British poets of the Romantic era is meant to illustrate how the reactions of both nobility and commoners are recorded in literature and media. The dual perception of Napoleon as both hero and tyrant and the atrocious suffering of those at home and bloody battles are manifest in the works of the major poets, William Wordsworth, Samuel Taylor Coleridge, Percy Bysshe Shelly, and especially George Gordon, Lord Byron. Even today, Napoleon transcends precise definition and he has inspired some of the greatest poets in British literature

OBJECTIVE: Off-label prescription is a common practice in psychiatry, raising health and economic concerns. Collegial consultation could allow a framed prescription of treatments that are not authorized in specific indications. Attention Deficit Hyperactivity in adult populations (ADHD) is a striking example of a pathology where off-label prescription is frequent. First considered to be a childhood disorder, the awareness of this condition in adults is increasing, leading to the development of new clinical practices and treatments. However, the adult ADHD diagnosis and its management are still emerging in France despite a high prevalence. Treatment of adult ADHD relies on methylphenidate prescription, but the initiation of this drug is not authorized in adult populations. Methylphenidate is a central nervous system stimulant that is structurally close to amphetamine and acts as a norepinephrine and dopamine reuptake inhibitor. Due to these pharmacological properties, neuropsychiatric and cardiovascular side-effects could occur. Furthermore, its addictive potential has led France to classify it as a psychoactive drug, dispensed via secured prescription. The first prescription and the one-year follow-up are restricted to neurologists, paediatrics, psychiatrists and sleep disorders specialists at hospital. The objective of this article is to propose a multidisciplinary framework for the off-label prescription of methylphenidate in adult ADHD. METHODS: The Multidisciplinary Advice Consultation for Exceptional Addiction Treatments (Consultation d'Avis Multidisciplinaire de Traitements d'Exception en Addictologie CAMTEA) was first set up in Lille for the prescription of baclofen in alcohol dependence and was then extended to topiramate in binge eating disorder. This procedure has been adapted to the particularities of ADHD in adult populations, the differential diagnosis (bipolar disorder, depressive disorder, anxious disorder, personality disorder, substance use disorder) and the co-morbidities requiring a full psychiatric and neuropsychological assessment. Moreover, a particular attention has been paid to the monitoring of neuropsychiatric, cardiovascular and misuse risk because of the potential side-effects of methylphenidate. RESULTS: The proposed prescription framework is structured into several specialized consultations. A first psychiatric evaluation aims to diagnose adult ADHD, using the French version of the Diagnostisch Interview Voor ADHD 2.0 questionnaire (DIVA 2.0), and to assess the quality of life impact with the Weiss Functional Inventory Rating Scale (WIFRS). It also searches for the presence of differential diagnosis or co-morbidities. The second appointment consists of a pharmacological evaluation that aims to search for contraindications and potential drug interaction. A neuropsychological evaluation based on standardized tests (Weschler Adulte Intelligence Scale [WAIS IV], Conner's Continuous Performance Test 3 [CPT] and the Minnesota Multiphasic Personnality Inventory [MMPI]) is also required to evaluate neurocognitive disabilities and personality features. Once the parameters of the different assessments have been collected, the synthesis is presented during a multidisciplinary meeting in order to assess the risk-benefit ratio for each patient. Several specialties are involved in this multidisciplinary meeting: psychiatry, addictology, general medicine, addictovigilance, pharmacovigilance and neuropsychology. One strategy among three possibilities can be decided: (1) contraindication to treatment with methylphenidate, (2) attention deficit disorder that does not require medication management, and (3) indication of treatment with methylphenidate with the choice of the pharmacological form (immediate or prolonged release). A biological check-up and an electrocardiogram are carried out systematically before any treatment. If the decision is made to initiate treatment, it is started at the lowest dosage and followed by a titration phase. A weekly follow-up is carried out during the titration phase in order to assess treatment efficacy and safety. After treatment stabilization, the general practitioner can carry out the renewal, and the patient will be reassessed within the framework of the multidisciplinary consultation every 3 months. CONCLUSIONS: When an off-label prescription is being considered, it must comply with the basic rules of good clinical practice, and the benefit/risk ratio should be constantly reassessed. The proposed multidisciplinary framework, adapted to the characteristics of adult ADHD and the pharmacological properties of methylphenidate, appears to be an interesting strategy to meet the requirements of the good clinical practice. The complementary assessments carried out and the collegial framework allow enhancing the patient's follow-up and minimize the drug risk, particularly in the psychiatric, addictive and cardiovascular adverse events. Finally, this framework could also help the monitoring of other off-label treatments for ADHD, such as atomoxetine or guanfacine.

Possible alterations of maternal immune function due to psychological stress may reflect immunoactive factor levels in breast milk. This study aimed to assess the association between maternal distress and breast milk levels of secretory IgA (SIgA), IgM, IgG, and lactoferrin (LF). We hypothesized that this association is moderated by maternal social support achieved from others during lactation. The study group included 103 lactating mothers and their healthy five-month-old infants. Maternal distress was determined based on the State Anxiety Inventory and the level of salivary cortisol. Social support was assessed using the Berlin Social Support Scales. Breast milk samples were collected to test for SIgA, IgM, IgG, and LF using the ELISA method. Milk immunoactive factors were regressed against maternal anxiety, social support, salivary cortisol, and infant gestational age using the general regression model. Maternal anxiety was negatively associated with milk levels of LF (β = −0.23, p = 0.028) and SIgA (β = −0.30, p = 0.004), while social support was positively associated with milk IgG (β = 0.25, p = 0.017). Neither anxiety nor social support were related to milk IgM. No association was found between the level of maternal salivary cortisol and immunoactive factors in milk. Our results suggest that maternal psychological wellbeing and social support may affect milk immune properties.

This article discusses the impact of a lockdown caused by the novel coronavirus disease 2019 on the educational process at a selected faculty of a public university in the Czech Republic focused on economic education. The aim was to capture relevant aspects in the context of impacts on the management of the educational process in the organization. The unique situation brought the possibility of analyzing the flexibility of the organization, its ability to adapt. A questionnaire survey was conducted among academics. We found out how they coped with this situation, their technical equipment, support from the faculty, and whether they encountered any problems. The goal of the article was not to bring an exact evaluation of selected questions, but to show the state of the actual situation, to point out possible problems of users, and to link these things with the approach to the management of the organization. Based on the analysis, we bring suggestions and recommendations for improving the process of transition to online learning as well as distance education management and recommendation to support teaching, regardless of the teacher's workplace. The basic areas and activities that need to be managed were also identified. Web of Science 12 2 art. no. 75

BACKGROUND Several biomarkers of inflammation and coagulation were reported to be associated with HIV disease progression in different settings. In this article, we report the association between 11 biomarkers and medium-term mortality in HIV-infected West African adults. METHODS In Temprano ANRS 12136, antiretroviral therapy (ART)-naive HIV-infected adults with high CD4 counts were randomly assigned either to start ART immediately or defer ART until the World Health Organization criteria were met. Participants who completed the 30-month trial follow-up were invited to participate in a posttrial phase. The posttrial phase end point was all-cause death. We used multivariate Cox proportional models to analyze the association between baseline plasma biomarkers [IL-1ra, IL-6, soluble vascular cell adhesion molecule 1 (sVCAM-1), sCD14, D-dimer, fibrinogen, IP-10, sCD163, albumin, high-sensitivity C-reactive protein, and 16S rDNA] and all-cause death in the Temprano participants randomized to defer ART. RESULTS Four hundred seventy-seven patients (median age 35 years, 78% women, and median CD4 count: 379 cells/mm) were randomly assigned to defer starting ART until the World Health Organization criteria were met. The participants were followed for 2646 person-years (median 5.8 years). In the follow-up, 89% of participants started ART and 30 died. In the multivariate analysis adjusted for the study center, sex, baseline CD4 count, isoniazid preventive therapy, plasma HIV-1 RNA, peripheral blood mononuclear cell HIV-1 DNA, and ART, the risk of death was significantly associated with baseline sVCAM-1 (≥1458 vs.

Simple Summary This is a novel description of (Pro)renin receptor (PRR) protein and its prognostic role in invasive urothelial cancer of the bladder. Using a tissue microarray, we investigated PRR expression and other immunohistochemical markers including p53, immune-checkpoint inhibition, and basal and luminal phenotypes in a series of patients with invasive urothelial carcinoma of the bladder treated with radical cystectomy. PRR expression is an independent prognostic marker and could be a potential target in urothelial carcinoma that should be further investigated. Abstract (Pro)renin receptor (PRR) is being investigated in several malignancies as it activates pathogenic pathways that contribute to cell proliferation, immunosuppressive microenvironments, and acquisition of aggressive neoplastic phenotypes. Its implication in urothelial cancer (UC) has not been evaluated so far. We retrospectively evaluate the prognostic role of PRR expression in a series of patients with invasive UC treated with radical cystectomy and other clinical and histopathological parameters including p53, markers of immune-checkpoint inhibition, and basal and luminal phenotypes evaluated by tissue microarray. Cox regression analyses using stepwise selection evaluated candidate prognostic factors and disease-specific survival. PRR was expressed in 77.3% of the primary tumors and in 70% of positive lymph nodes. PRR expression correlated with age (p = 0.006) and was associated with lower preoperatively hemoglobin levels. No other statistical association was evidenced with clinical and pathological variables (gender, ASA score, Charlson comorbidity index, grade, pT, pN) or immunohistochemical expressions evaluated (CK20, GA-TA3, CK5/6, CD44, PD-L1, PD-1, B7-H3, VISTA, and p53). PRR expression in primary tumors was associated with worse survival (log-rank, p = 0.008). Cox regression revealed that PRR expression (HR 1.85, 95% CI 1.22–2.8), pT (HR 7.02, 95% CI 2.68–18.39), pN (HR 2.3, 95% CI 1.27–4.19), and p53 expression (HR 1.95, 95% CI 1.1–3.45) were independent prognostic factors in this series. In conclusion, we describe PRR protein and its prognostic role in invasive UC for the first time. Likely mechanisms involved are MAPK/ERK activation, Wnt/β-catenin signaling, and v-ATPAse function.

(1). Background: Immunohistochemical (IHC) evaluation of programmed death-1 (PD-1) and its ligand (PD-L1) is being used to evaluate advanced malignancies with potential response to immune checkpoint inhibitors. We evaluated both plasma and tissue expression of PD-1 and PD-L1 in the same cohort of patients, including non-metastatic and metastatic clear cell renal cell carcinoma (CCRCC). Concomitant plasma and tissue expression of PD-1 and PD-L1 was evaluated with emphasis on diagnostic and prognostic implications. (2) Methods: we analyzed PD-1 and PD-L1 IHC expression in tumor tissues and soluble forms (sPD-1 and sPD-L1) in plasma from 89 patients with CCRCC, of which 23 were metastatic and 16 received systemic therapy. The primary endpoint was evaluation of overall survival using Kaplan-Meier analysis and the Cox regression model. Plasma samples from healthy volunteers were also evaluated. (3) Results: Interestingly, sPD-1 and sPD-L1 levels were lower in cancer patients than in controls. sPD-1 and sPD-L1 levels and their counterpart tissue expression both at the tumor center and infiltrating front were not associated. Higher expression of both PD-1 and PD-L1 were associated with tumor grade, necrosis and tumor size. PD-1 was associated to tumor stage (pT) and PD-L1 to metastases. sPD-1 and sPD-L1 were not associated with clinico-pathological parameters, although both were higher in patients with synchronous metastases compared to metachronous ones and sPD-L1 was also higher for metastatic patients compared to non-metastatic patients. sPD-1 was also associated with the International Metastatic Renal Cell Cancer Database Consortium (IMDC) prognostic groups in metastatic CCRCC and also to the Morphology, Attenuation, Size and Structure (MASS) response criteria in metastatic patients treated with systemic therapy, mainly tyrosine-kinase inhibitors. Regarding prognosis, PD-L1 immunostaining at the tumor center with and without the tumor front was associated with worse survival, and so was sPD-L1 at a cut-off &gt, 793 ng/mL. Combination of positivity at both the tissue and plasma level increased the level of significance to predict prognosis. (4) Conclusions: Our findings corroborate the role of PD-L1 IHC to evaluate prognosis in CCRCC and present novel data on the usefulness of plasma sPD-L1 as a promising biomarker of survival in this neoplasia.

Background Asymptomatic HIV-infected people who start ART early may feel less motivated and neglect compliance. This might promote the emergence of resistance. Methods In the Temprano trial, ART-naive HIV-infected adults with high CD4 counts were randomly assigned to start ART immediately (immediate group) or defer ART until the WHO criteria were met (deferred group). All participants were monitored for 30 months. Those in the deferred group who started ART were monitored for longer, until they had completed 30 months on ART. We compared the rate of virological failure and drug resistance between the immediate and deferred groups 30 months after ART initiation. Results Of the 2056 participants in Temprano, 1033 were assigned to start ART immediately and 1023 to defer ART. Of the latter, 488 started ART during trial follow-up. Patients in the deferred group who started ART had a lower median CD4 count (280 versus 465 cells/mm3) and a higher median plasma HIV-1 RNA (5.1 versus 4.7 log10 copies/mL) at baseline. During follow-up, participants in both groups had similar antiretroviral drug exposure. Thirty months after ART initiation, patients in the deferred group had a higher rate of virological failure (35.3% versus 29.9%, P = 0.04) and a lower genotypic susceptibility score (P = 0.04). Conclusions Starting ART early decreases the risk of virological failure and drug resistance in the medium term. This benefit is of particular importance in countries where access to viral load monitoring and the number of antiretroviral drug lines is limited.

Multitask learning helps to obtain a meaningful representation of the data, retaining a small number of parameters needed to train the model. In natural language processing, models often reach as many as a few hundred million trainable parameters, which makes adaptations to new tasks computationally infeasible. Creating shareable layers for multiple tasks allows to spare resources and often leads to better data representation. In this work, we propose a new approach to train a BERT model in a multitask setup, which we call EmBERT. To introduce information about the task, we inject task-specific embeddings to the multi-head attention layers. Our modified architecture requires a minimal number of additional parameters relative to the original BERT model (+0.025% per task) while achieving state-of-the-art results in the GLUE benchmark.

Lichens are unique organisms, valued for their pharmacological activity, but also well known as bioindicators of environmental pollution, key determinants for some natural ecological habitats, or just popular elements of decoration. High morphological similarity between lichen species makes their recognition complicated, especially under in-field conditions. Thus, there is a need for a quick and easy method that can help with the preliminary classification of selected lichen species. This paper presents a tool that can facilitate the recognition of Cladonia lichen species, based on a deep convolutional neural network, a model which has nowadays reached a classification level often comparable to humans. The network was trained and tested on twelve Cladonia species using a total of 1164 images, downloaded from various websites. The trained model achieved 60.94% accuracy, which is satisfactory for this novel, but still preliminary, automated classification of lichen species.

Background: Renal cancer is one of the most frequent malignancies in Western countries, with an unpredictable clinical outcome, partly due to its high heterogeneity and the scarcity of reliable biomarkers of tumour progression. (Pro)renin receptor (PRR) is a novel receptor of the renin-angiotensin system (RAS) that has been associated with the development and progression of some solid tumours by RAS-dependent and -independent mechanisms. (2) Methods: In this study, we analysed the immunohistochemical expression of PRR at the centre and border in a series of 83 clear-cell renal cell (CCRCCs), 19 papillary (PRCC) and 7 chromophobe (ChRCC) renal cell carcinomas, and the benign tumour renal oncocytoma (RO, n = 11). (3) Results: PRR is expressed in all the tumour subtypes, with higher mean staining intensity in ChRCCs and ROs. A high expression of PRR at the tumour centre and at the infiltrative front of CCRCC tissues is significantly associated with high grade, tumour diameter, local invasion and stage, and with high mortality risk by UCLA integrated staging system (UISS) scale. (4) Conclusions: These findings indicate that PRR is associated with the development and progression of renal tumours. Its potential as a novel biomarker for RCC diagnosis/prognosis and as a promising therapeutic target should be taken into account in the future. Basque Government (ELKARTEK KK2018-00090 and KK-2020/00069) 3.992 JCR (2021) Q2, 60/172 Medicine, General & Internal 0.658 SJR (2021) Q2, 56/119 Clinical Biochemistry No data IDR 2021 UEM

Multiple sclerosis (MS) is a neurodegenerative disease with a complex autoimmune component, and it has a high prevalence among middle-aged females. The manifestations of the disease range from episodic somatosensory dysfunction to progressive and permanent central nervous system (CNS) damage. Due to a high prevalence of psychiatric comorbidities and proven abnormalities in serotonin (5-HT) levels among MS patients, they are usually on drugs that modify the serotonergic system. Through a comprehensive literature review of studies published in the last 10 years related to 5-HT in MS and its therapeutic applications, we aimed to elucidate the mechanism behind the neurotransmitter (NT) levels' abnormalities. Most importantly, we endeavored to gather the most up-to-date information about the full therapeutic potential of agents acting on this system. We discovered that multiple processes cause low levels of 5-HT in MS patients. The varying levels of the availability of the 5-HT transporter (SERT) in the CNS decreasing overall tryptophan (TRP) levels, and diversion of the amino acid away from its synthetic pathway constitute some of those. Studies in animals have shown that 5-HT levels' elevations could cause immune-modulating effects and could probably slow down the disease progression rate. Human studies have shown a more diverse and complex response. Promising results have been obtained in the last 10 years regarding 5-HT's immune-modulatory role in MS patients and its therapeutic applications. Human studies with a larger population and feasible designs are still needed to fully ascertain the effects of serotonin on the immune system and disease progression in patients with MS.

Colorectal cancer (CRC) is the second cause of death in men and the third in women. This work deals with the study of the low molecular weight protein fraction of sera from patients who underwent surgery for CRC and who were followed for several years thereafter. MALDI-TOF MS was used to identify serum peptidome profiles of healthy controls, non-metastatic CRC patients and metastatic CRC patients. A multiple regression model was applied to signals preliminarily selected by SAM analysis to take into account the age and gender differences between the groups. We found that, while a signal m/z 2021.08, corresponding to the C3f fragment of the complement system, appears significantly increased only in serum from metastatic CRC patients, a m/z 1561.72 signal, identified as a prothrombin fragment, has a significantly increased abundance in serum from non-metastatic patients as well. The findings were also validated by a bootstrap resampling procedure. The present results provide the basis for further studies on large cohorts of patients in order to confirm C3f and prothrombin as potential serum biomarkers. Thus, new and non-invasive tests might be developed to improve the classification of colorectal cancer. This work was supported by grants from Italian Ministry of Health (5×1000 Funds 2013 and 2015) and IT8-11/13 from the Basque Government.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Coronary artery disease (CAD) is a significant contributor to mortality in America. A common risk factor of CAD is hyperlipidemia. Treatment guidelines of hyperlipidemia are well established. Statins are the cornerstone of treating hyperlipidemia. New medications such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) have also illustrated significant results in treating hyperlipidemia. While multiple studies exemplify the disparities in statin and PCSK9 inhibitors utilization to reduce CAD mortality and risk factors, there are no systematic reviews to validate these disparities. We conducted a search on PubMed, including Medline and PubMed Central, and Google Scholar. For this analysis, we selected articles published between 2000 and 2020 and those that fit the inclusion and exclusion criteria. Based on the type of study, we performed appropriate quality assessments and deleted studies with a score of less than seven or with a high risk of biases. The search strategy resulted in 322 studies. After inclusion and exclusion criteria were applied, we included 20 articles in the analysis of this review. This systematic review demonstrates that non-white races and women were less likely to receive the correct, clinically indicated, therapy for hyperlipidemia. A multi-faceted approach is required to solve this inequality in healthcare.

We investigate the problem of training neural networks from incomplete images without replacing missing values. For this purpose, we first represent an image as a graph, in which missing pixels are entirely ignored. The graph image representation is processed using a spatial graph convolutional network (SGCN) -- a type of graph convolutional networks, which is a proper generalization of classical CNNs operating on images. On one hand, our approach avoids the problem of missing data imputation while, on the other hand, there is a natural correspondence between CNNs and SGCN. Experiments confirm that our approach performs better than analogical CNNs with the imputation of missing values on typical classification and reconstruction tasks.

It has been proposed that women&rsquo, s physical attractiveness is a cue to temporal changes in fertility. If this is the case, we should observe shifts in attractiveness during pregnancy&mdash, a unique physiological state of temporal infertility. The aim of this study was to examine how women&rsquo, s facial attractiveness changes during the subsequent trimesters of pregnancy and how it compares to that of nonpregnant women. Sixty-six pictures of pregnant women (22 pictures per trimester) and 22 of nonpregnant women (a control group) were used to generate four composite portraits, which were subsequently assessed for facial attractiveness by 117 heterosexual men. The results show considerable differences between facial attractiveness ratings depending on the status and progress of pregnancy. Nonpregnant women were perceived as the most attractive, and the attractiveness scores of pregnant women decreased throughout the course of pregnancy. Our findings show that facial attractiveness can be influenced by pregnancy and that gestation, even at its early stages, affects facial attractiveness. Considerable changes in women&rsquo, s physiology that occur during pregnancy may be responsible for the observed effects.

Background We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface and air contamination during the coronavirus disease 2019 (COVID-19) pandemic in London. Methods Prospective, cross-sectional, observational study in a multisite London hospital. Air and surface samples were collected from 7 clinical areas occupied by patients with COVID-19 and a public area of the hospital. Three or four 1.0-m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected using reverse-transcription quantitative polymerase chain reaction (PCR) and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. Results Viral RNA was detected on 114 of 218 (52.3%) surfaces and in 14 of 31 (38.7%) air samples, but no virus was cultured. Viral RNA was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67 of 105 [63.8%] vs 29 of 64 [45.3%]; odds ratio, 0.5; 95% confidence interval, 0.2–0.9; P = .025, χ2 test). The high PCR cycle threshold value for all samples (>30) indicated that the virus would not be culturable. Conclusions Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19 and the need for effective use of personal protective equipment, physical distancing, and hand/surface hygiene.

BackgroundEvaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London.MethodsWe performed this prospective cross-sectional observational study in a multi-site London hospital. Air and surface samples were collected from seven clinical areas, occupied by patients with COVID-19, and a public area of the hospital. Three or four 1.0 m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined.ResultsViral RNA was detected on 114/218 (52.3%) of surfaces and 14/31 (38.7%) air samples but no virus was cultured. The proportion of surface samples contaminated with viral RNA varied by item sampled and by clinical area. Viral RNA was detected on surfaces i and in air in public areas of the hospital but was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67/105 (63.8%) vs. 29/64 (45.3%) (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Chi squared test)). The high PCR Ct value for all samples (>30) indicated that the virus would not be culturable.ConclusionsOur findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19, and the need for effective use of PPE, physical distancing, and hand/surface hygiene.