Concentrations and sources of Cd, Cr, Cu, Fe, Ni, Pb and Zn in soil of the Mitidja plain, Algeria

peer reviewedIn the last few decades, the Mitidja plain has undergone economic development which may have altered the concentrations of some trace metals in its soils. Therefore, this study was aimed at investigating the concentrations and sources of Cd, Cr, Cu, Fe, Ni, Pb and Zn in 180 composite topsoil samples using a combination of environmental quality indicators and multivariate statistical approaches with a geographic information system (GIS). Based on spatial distribution maps, various hot-spots have been identified. Enrichment factors (EFs) indicated that Cd, Cu, Pb and Zn were from anthropogenic sources, while Ni and Cr were controlled mainly by natural lithogenic source. Multivariate statistical analyses were in agreement, except for Cu which was classified as coming from both anthropogenic and lithogenic sources. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group

Low Doses of Bisphenol A and Diethylstilbestrol Impair Ca(2+) Signals in Pancreatic α-Cells through a Nonclassical Membrane Estrogen Receptor within Intact Islets of Langerhans

Glucagon, secreted from pancreatic α-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In this article, we show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), at a concentration of 10(−9) M, suppressed low-glucose–induced intracellular calcium ion ([Ca(2+)](i)) oscillations in α-cells, the signal that triggers glucagon secretion. This action has a rapid onset, and it is reproduced by the impermeable molecule estradiol (E(2)) conjugated to horseradish peroxidase (E-HRP). Competition studies using E-HRP binding in immunocytochemically identified α-cells indicate that 17β-E(2), BPA, and DES share a common membrane-binding site whose pharmacologic profile differs from the classical ER. The effects triggered by BPA, DES, and E(2) are blocked by the Gαi- and Gα(o)-protein inhibitor pertussis toxin, by the guanylate cyclase–specific inhibitor 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one, and by the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. The effects are reproduced by 8-bromo-guanosine 3′,5′-cyclic monophosphate and suppressed in the presence of the cGMP-dependent protein kinase inhibitor KT-5823. The action of E(2), BPA, and DES in pancreatic α-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid

Epidemiology, prehospital care and outcomes of patients arriving by ambulance with dyspnoea: An observational study

Background: This study aimed to determine epidemiology and outcome for patients presenting to emergency departments (ED) with shortness of breath who were transported by ambulance. Methods: This was a planned sub-study of a prospective, interrupted time series cohort study conducted at three time points in 2014 and which included consecutive adult patients presenting to the ED with dyspnoea as a main symptom. For this sub-study, additional inclusion criteria were presentation to an ED in Australia or New Zealand and transport by ambulance. The primary outcomes of interest are the epidemiology and outcome of these patients. Analysis was by descriptive statistics and comparisons of proportions. Results: One thousand seven patients met inclusion criteria. Median age was 74 years (IQR 61-68) and 46.1 % were male. There was a high rate of co-morbidity and chronic medication use. The most common ED diagnoses were lower respiratory tract infection (including pneumonia, 22.7 %), cardiac failure (20.5%) and exacerbation of chronic obstructive pulmonary disease (19.7 %). ED disposition was hospital admission (including ICU) for 76.4 %, ICU admission for 5.6 % and death in ED in 0.9 %. Overall in-hospital mortality among admitted patients was 6.5 %. Discussion: Patients transported by ambulance with shortness of breath make up a significant proportion of ambulance caseload and have high comorbidity and high hospital admission rate. In this study, >60 % were accounted for by patients with heart failure, lower respiratory tract infection or COPD, but there were a wide range of diagnoses. This has implications for service planning, models of care and paramedic training. Conclusion: This study shows that patients transported to hospital by ambulance with shortness of breath are a complex and seriously ill group with a broad range of diagnoses. Understanding the characteristics of these patients, the range of diagnoses and their outcome can help inform training and planning of services

Pre-hospital management protocols and perceived difficulty in diagnosing acute heart failure

Aim To illustrate the pre-hospital management arsenals and protocols in different EMS units, and to estimate the perceived difficulty of diagnosing suspected acute heart failure (AHF) compared with other common pre-hospital conditions. Methods and results A multinational survey included 104 emergency medical service (EMS) regions from 18 countries. Diagnostic and therapeutic arsenals related to AHF management were reported for each type of EMS unit. The prevalence and contents of management protocols for common medical conditions treated pre-hospitally was collected. The perceived difficulty of diagnosing AHF and other medical conditions by emergency medical dispatchers and EMS personnel was interrogated. Ultrasound devices and point-of-care testing were available in advanced life support and helicopter EMS units in fewer than 25% of EMS regions. AHF protocols were present in 80.8% of regions. Protocols for ST-elevation myocardial infarction, chest pain, and dyspnoea were present in 95.2, 80.8, and 76.0% of EMS regions, respectively. Protocolized diagnostic actions for AHF management included 12-lead electrocardiogram (92.1% of regions), ultrasound examination (16.0%), and point-of-care testings for troponin and BNP (6.0 and 3.5%). Therapeutic actions included supplementary oxygen (93.2%), non-invasive ventilation (80.7%), intravenous furosemide, opiates, nitroglycerine (69.0, 68.6, and 57.0%), and intubation 71.5%. Diagnosing suspected AHF was considered easy to moderate by EMS personnel and moderate to difficult by emergency medical dispatchers (without significant differences between de novo and decompensated heart failure). In both settings, diagnosis of suspected AHF was considered easier than pulmonary embolism and more difficult than ST-elevation myocardial infarction, asthma, and stroke. Conclusions The prevalence of AHF protocols is rather high but the contents seem to vary. Difficulty of diagnosing suspected AHF seems to be moderate compared with other pre-hospital conditions

Monomorphic epitheliotropic intestinal T-cell lymphoma comprises morphologic and genomic heterogeneity impacting outcome.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males; 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e. nonmonomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ (98%) CD4- (94%) CD5- (97%) CD7+ (97%) CD8+ (90%) CD56+ (86%) CD103+ (80%) cytotoxic marker+ (98%)) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with nonmonomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%) JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signalling and encompasses genetic and morphologic variants associated with very high clinical risk

Predictive value of S100-B and copeptin for outcomes following seizure: the BISTRO International Cohort Study.

OBJECTIVE: To evaluate the performance of S100-B protein and copeptin, in addition to clinical variables, in predicting outcomes of patients attending the emergency department (ED) following a seizure. METHODS: We prospectively included adult patients presented with an acute seizure, in four EDs in France and the United Kingdom. Participants were followed up for 28 days. The primary endpoint was a composite of seizure recurrence, all-cause mortality, hospitalization or rehospitalisation, or return visit in the ED within seven days. RESULTS: Among the 389 participants included in the analysis, 156 (40%) experienced the primary endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B (0.11 μg/l [95% CI 0.07-0.20] vs 0.09 μg/l [0.07-0.14]) and copeptin (23 pmol/l [9-104] vs 17 pmol/l [8-43]) were higher in participants meeting the primary endpoint. However, both biomarkers were poorly predictive of the primary outcome with a respective area under the receiving operator characteristic curve of 0.57 [0.51-0.64] and 0.59 [0.54-0.64]. Multivariable logistic regression analysis identified higher age (odds ratio [OR] 1.3 per decade [1.1-1.5]), provoked seizure (OR 4.93 [2.5-9.8]), complex partial seizure (OR 4.09 [1.8-9.1]) and first seizure (OR 1.83 [1.1-3.0]) as independent predictors of the primary outcome. A second regression analysis including the biomarkers showed no additional predictive benefit (S100-B OR 3.89 [0.80-18.9] copeptin OR 1 [1.00-1.00]). CONCLUSION: The plasma biomarkers S100-B and copeptin did not improve prediction of poor outcome following seizure. Higher age, a first seizure, a provoked seizure and a partial complex seizure are independently associated with adverse outcomes

Overview of the TCV tokamak experimental programme

The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with \u27small\u27 (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe