The Influence of Workload and Work Flexibility on Work-Life Conflict and the Role of Emotional Exhaustion

The purpose of this study is to examine the relationship between contextual work-related factors in terms of job demands (workload—WL) and job resources (work flexibility—WF), work–life conflict (WLC) and the burnout dimension emotional exhaustion (EE) in a large population-based sample. Building on the job demands resources model (JDRM), we have developed the hypothesis that WL has an indirect effect on EE that is mediated by WLC. We conducted a secondary analysis using data from the Dresden Burnout Study (DBS, N = 4246, mean age (SD) = 42.7 years (10.5); 36.4% male). Results from structural equation modelling revealed that EE is positively associated with WL (β = 0.15, p = 0.001) and negatively associated with WF (β = −0.13, p = 0.001), also after accounting for potential confounding variables (demography, depressive symptoms, and lifetime diagnosis of burnout). Both effects are mediated by WLC (β = 0.18; p = 0.001 and β = 0.08; p = 0.001, respectively) highlighting the important role of WLC in employee health. In summary, WF may help to reduce burnout symptoms in employees, whereas WL may increase them. Study results suggest that both associations depend on WLC levels

Impact of rifaximin on the frequency and characteristics of spontaneous bacterial peritonitis in patients with liver cirrhosis and ascites

BACKGROUND: Rifaximin is a non-absorbable antibiotic used to prevent relapses of hepatic encephalopathy which may also be a candidate for prophylaxis of spontaneous bacterial peritonitis (SBP). AIM: To detect the impact of rifaximin on the occurrence and characteristics of SBP. METHODS: We prospectively studied all hospitalized patients that underwent a diagnostic paracentesis in our department from March 2012 to April 2013 for SBP and recorded all clinical data including type of SBP prophylaxis, prior use of rifaximin, concomitant complications of cirrhosis, as well as laboratory results and bacteriological findings. Patients were divided into the following three groups: no antibiotic prophylaxis, prophylaxis with rifaximin or with systemically absorbed antibiotic prophylaxis. RESULTS: Our study cohort comprised 152 patients with advanced liver cirrhosis, 32 of whom developed SBP during the study period. As expected, our study groups differed regarding a history of hepatic encephalopathy and SBP before inclusion into the study. None of the 17 patients on systemic antibiotic prophylaxis developed SBP while 8/27 patients on rifaximin and 24/108 without prophylaxis had SBP (p = 0.02 and p = 0.04 versus systemic antibiotics, respectively). In general, episodes of SBP were similar for patients treated with rifaximin and those without any prophylaxis. However, Escherichia coli and enterococci were dominant in the ascites of patients without any prophylaxis, while mostly klebsiella species were recovered from the ascites samples in the rifaximin group. CONCLUSION: Rifaximin pretreatment did not lead to a reduction of SBP occurrence in hospitalized patients with advanced liver disease. However, the bacterial species causing SBP were changed by rifaximin

Stability of Closed Timelike Curves in Goedel Universe

We study, in some detail, the linear stability of closed timelike curves in the Goedel metric. We show that these curves are stable. We present a simple extension (deformation) of the Goedel metric that contains a class of closed timelike curves similar to the ones associated to the original Goedel metric. This extension correspond to the addition of matter whose energy-momentum tensor is analyzed. We find the conditions to have matter that satisfies the usual energy conditions. We study the stability of closed timelike curves in the presence of usual matter as well as in the presence of exotic matter (matter that does satisfy the above mentioned conditions). We find that the closed timelike curves in Goedel universe with or whithout the inclusion of regular or exotic matter are also stable under linear perturbations. We also find a sort of structural stability.Comment: 12 pages, 11 figures, RevTex, several typos corrected. GRG, in pres

Drugs for neglected tropical diseases : availability of age-appropriate oral formulations for young children

It is recognised that paediatric indications and age-appropriate formulations are required to ensure that paediatric populations receive appropriate pharmacotherapeutic treatment. The lack of information on dosing, efficacy and safety data (labelling) is a well-recognised problem for all diseases affecting children. For neglected tropical diseases, the fact that they affect to a large extent poor and marginalised populations in low- and middle-income countries means that there is a low economic return on investment into paediatric development activities compared to other diseases [e.g. human immunodeficiency virus (HIV)]. This review provides an introduction to issues affecting the availability and development of paediatric population-relevant data and appropriate formulations of drugs for NTDs. We are summarising why age-appropriate formulations are important to ensure treatment efficacy, safety and effectiveness, outline initiatives to increase the number of paediatric indications/labelling and age-appropriate formulations, provide an overview of publicly available information on the formulations of oral drugs for NTDs relative to age appropriateness and give an introduction to options for age-appropriate formulations. The review completes with ‘case studies’ of recently developed paediatric formulations for NTDs, complemented by case studies for fixed-dose combinations for HIV infection in children since such formulations have not been developed for NTDs. Graphical Abstract: [Figure not available: see fulltext.]

Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1% each), as well as in VHL, BRAF, MLH1, TP53 and RET (3% each). Moreover, NRAS, KRAS and ATM mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored

The pipeline for drugs for control and elimination of neglected tropical diseases : 2. Oral anti-infective drugs and drug combinations for off-label use

In its ‘Road map for neglected tropical diseases 2021–2030’, the World Health Organization outlined its targets for control and elimination of neglected tropical diseases (NTDs) and research needed to achieve them. For many NTDs, this includes research for new treatment options for case management and/or preventive chemotherapy. Our review of small-molecule anti-infective drugs recently approved by a stringent regulatory authority (SRA) or in at least Phase 2 clinical development for regulatory approval showed that this pipeline cannot deliver all new treatments needed. WHO guidelines and country policies show that drugs may be recommended for control and elimination for NTDs for which they are not SRA approved (i.e. for ‘off-label’ use) if efficacy and safety data for the relevant NTD are considered sufficient by WHO and country authorities. Here, we are providing an overview of clinical research in the past 10 years evaluating the anti-infective efficacy of oral small-molecule drugs for NTD(s) for which they are neither SRA approved, nor included in current WHO strategies nor, considering the research sponsors, likely to be registered with a SRA for that NTD, if found to be effective and safe. No such research has been done for yaws, guinea worm, Trypanosoma brucei gambiense human African trypanosomiasis (HAT), rabies, trachoma, visceral leishmaniasis, mycetoma, T. b. rhodesiense HAT, echinococcosis, taeniasis/cysticercosis or scabies. Oral drugs evaluated include sparfloxacin and acedapsone for leprosy; rifampicin, rifapentin and moxifloxacin for onchocerciasis; imatinib and levamisole for loiasis; itraconazole, fluconazole, ketoconazole, posaconazole, ravuconazole and disulfiram for Chagas disease, doxycycline and rifampicin for lymphatic filariasis; arterolane, piperaquine, artesunate, artemether, lumefantrine and mefloquine for schistosomiasis; ivermectin, tribendimidine, pyrantel, oxantel and nitazoxanide for soil-transmitted helminths including strongyloidiasis; chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B, ivermectin and doxycycline for dengue; streptomycin, amoxicillin, clavulanate for Buruli ulcer; fluconazole and isavuconazonium for mycoses; clarithromycin and dapsone for cutaneous leishmaniasis; and tribendimidine, albendazole, mebendazole and nitazoxanide for foodborne trematodiasis. Additional paths to identification of new treatment options are needed. One promising path is exploitation of the worldwide experience with ‘off-label’ treatment of diseases with insufficient treatment options as pursued by the ‘CURE ID’ initiative. Graphical abstract: [Figure not available: see fulltext.]

Goedel-type Universes and the Landau Problem

We point out a close relation between a family of Goedel-type solutions of 3+1 General Relativity and the Landau problem in S^2, R^2 and H_2; in particular, the classical geodesics correspond to Larmor orbits in the Landau problem. We discuss the extent of this relation, by analyzing the solutions of the Klein-Gordon equation in these backgrounds. For the R^2 case, this relation was independently noticed in hep-th/0306148. Guided by the analogy with the Landau problem, we speculate on the possible holographic description of a single chronologically safe region.Comment: Latex, 21 pages, 1 figure. v2 missing references to previous work on the subject adde

Differential susceptibility of Onchocerca volvulus microfilaria to ivermectin in two areas of contrasting history of mass drug administration in Cameroon: relevance of microscopy and molecular techniques for the monitoring of skin microfilarial repopulation within six months of direct observed treatment

Background Ivermectin is an excellent microfilaricide against Onchocerca volvulus. However, in some regions, long term use of ivermectin has resulted in sub-optimal responses to the treatment. More data to properly document the phenomenon in various contexts of ivermectin mass drug administration (IVM-MDA) is needed. Also, there is a need to accurately monitor a possible repopulation of skin by microfilariae following treatment. Skin snip microscopy is known to have a low sensitivity in individuals with light infections, which can be the case following treatment. This study was designed with two complementary objectives: (i) to assess the susceptibility of O. volvulus microfilariae to ivermectin in two areas undergoing IVM-MDA for different lengths of time, and (ii) to document the repopulation of skin by the O. volvulus microfilariae following treatment, using 3 independent diagnostic techniques. Method Identified microfilaridermic individuals were treated with ivermectin and re-examined after 1, 3, and 6 months using microscopy, actin real-time PCR (actin-qPCR) and O-150 LAMP assays. Susceptibility to ivermectin and trends in detecting reappearance of skin microfilariae were determined using three techniques. Microscopy was used as an imperfect gold standard to determine the performance of actin-qPCR and LAMP. Results In Bafia with over 20 years of IVM-MDA, 11/51 (21.6%) direct observe treated microfilaridemic participants were still positive for skin microfilariae after 1 month. In Melong, with 10 years of IVM-MDA, 2/29 (6.9%) treated participants were still positive. The microfilarial density reduction per skin biopsy within one month following treatment was significantly lower in participants from Bafia. In both study sites, the molecular techniques detected higher proportions of infected individuals than microscopy at all monitoring time points. LAMP demonstrated the highest levels of sensitivity and real-time PCR was found to have the highest specificity. Conclusion Patterns in skin mirofilariae clearance and repopulation were established. O. volvulus worms from Bafia with higher number of annual MDA displayed a lower clearance and higher repopulation rate after treatment with ivermectin. Molecular assays displayed higher sensitivity in monitoring O. volvulus microfilaridemia within six months following treatment

Unraveling cross-reactivity of anti-glycan IgG responses in filarial nematode infections

Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of infection in certain areas, but limitations of current diagnostics for population surveillance have been pointed out and improved assays are needed to reach the elimination targets. While serological tests detecting antibodies to parasite antigens are convenient tools, those currently available are compromised by the occurrence of antibodies cross-reactive between nematodes, as well as by the presence of residual antibodies in sera years after treatment and clearance of the infection. We recently characterized the N-linked and glycosphingolipid derived glycans of the parasitic nematode Brugia malayi and revealed the presence of various antigenic structures that triggered immunoglobulin G (IgG) responses in infected individuals. To address the specificity of IgG binding to these glycan antigens, we screened microarrays containing Brugia malayi glycans with plasma from uninfected individuals and from individuals infected with Loa loa, Onchocerca volvulus, Mansonella perstans and Wuchereria bancrofti, four closely related filarial nematodes. IgG to a restricted subset of cross-reactive glycans was observed in infection plasmas from all four species. In plasma from Onchocerca volvulus and Mansonella perstans infected individuals, IgG binding to many more glycans was additionally detected, resulting in total IgG responses similar to the ones of Brugia malayi infected individuals. For these infection groups, Brugia malayi, Onchocerca volvulus and Mansonella perstans, we further studied the different IgG subclasses to Brugia malayi glycans. In all three infections, IgG1 and IgG2 appeared to be the major subclasses involved in response to glycan antigens. Interestingly, in Brugia malayi infected individuals, we observed a marked reduction in particular in IgG2 to parasite glycans post-treatment with anthelminthic, suggesting a promising potential for diagnostic applications. Thus, we compared the IgG response to a broad repertoire of Brugia malayi glycans in individuals infected with various filarial nematodes. We identified broadly cross-reactive and more specific glycan targets, extending the currently scarce knowledge of filarial nematode glycosylation and host anti-glycan antibody response. We believe that our initial findings could be further exploited to develop disease-specific diagnostics as part of an integrated approach for filarial disease control.Host-parasite interactio

Restauration morpho-dynamique et redynamisation de la section court-circuitée du Rhin en aval du barrage de Kembs (projet INTERREG / EDF)

National audienceThe Upper Rhine River has been heavily impacted by channelization for flood protection and navigation, and then by damming for hydropower generation. In normal non flooding conditions, most of the flows are diverted in a canalized section whereas the regulated “old Rhine” bypassed reach runs a minimum flow. Between Huningue and Neuf-Brisach, engineering works induced simplification and stabilization of the channel pattern from a formerly braiding sector to a single incised channel, hydrological modifications, bottom armouring due to bedload decrease, and thus ecological alterations. Two complementary and interdisciplinary projects have been initiated to restore alluvial morphodynamics: i) the international “INTERREG IV - Redynamisation of the old Rhine” project (2009-2012) coordinated by the Alsace region, France; ii) the left bank “controlled erosion” project launched by Electricité de France (EDF) within Kembs hydroelectric station relicensing process since 2003-2004. The purpose of these projects is to evaluate the feasibility of an important hydro-morphological and ecological restoration plan on a 45 km long reach, through both field testing of bank erosion techniques at favourable locations, and artificial sediments input from right bank excavations. This will help define possible long term prospective scenarios, in order to restore sustainable sediment transport, morphodynamics variability and associated ecological functions. The study will involve historical analysis, hydro-morphological / hydraulic physical and numerical modelling, physical and ecological monitoring, and sociological aspectsLe Rhin alsacien-allemand a enregistré de profondes modifications morphologiques et hydrologiques à la suite de sa correction et de sa régularisation pour la protection contre les crues et la navigation, puis après la construction de barrages hydro-électriques. Les aménagements réalisés entre Huningue et Neuf-Brisach ont engendré une simplification et une stabilisation du style fluvial. Un fleuve en tresses a cédé la place à un chenal unique incisé. Le fond de chenal est devenu pavé à cause d’une diminution des apports de charge de fond et des altérations écologiques ont été observées (simplification des habitats aquatiques et riverains). Deux projets complémentaires et interdisciplinaires ont été engagés afin de restaurer une dynamique des formes alluviales : i) le projet international INTERREG IV – Redynamisation du Vieux Rhin (2009-2012) sous l’impulsion de la région Alsace ; ii) le projet d’érosion maitrisée des berges de la rive gauche conduit par Electricité de France (EDF) dans le cadre du renouvellement de la concession de l’aménagement de Kembs. L’objectif des deux projets est de définir un plan de restauration hydro-morphologique et écologique conduisant à la redynamisation d’un tronçon de 45 km. L’étude repose sur une analyse historique, l’exploitation de modèles à la fois physiques et numériques, et les suivis morphologiques in situ d’une recharge artificielle en sédiments et d’érosions de berge contrôlées. Ces études de faisabilité sont complétées par des analyses écologique et sociologique pour apprécier l’impact socio-environnemental de ces projets