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Human infections with Corynebacterium diphtheriae species complex (CdSC) bacteria were rare in French Guiana until 2016, when the number of cases diagnosed increased. We conducted an epidemiologic, multicenter, retrospective study of all human CdSC infections diagnosed in French Guiana during January 1, 2016-December 31, 2021. A total of 64 infectious episodes were observed in 60 patients; 61 infections were caused by C. diphtheriae and 3 by C. ulcerans. Estimated incidence increased from 0.7 cases/100,000 population in 2016 to 7.7 cases/100,000 population in 2021. The mean patient age was 30.4 (+23.7) years, and male-to-female ratio was 1.7:1 (38/22). Of the 61 C. diphtheriae isolates, 5 tested positive for the diphtheria toxin gene, and all results were negative by Elek test; 95% (61/64) of cases were cutaneous, including the C. ulcerans cases. The increase in reported human infections underscores the need to raise awareness among frontline healthcare practitioners to improve prevention. [ABSTRACT FROM AUTHOR]

Cannabis has long been stigmatized as an illicit drug. Since legalization in Canada for both medical and recreational purposes, older adults' cannabis consumption has increased more than any other age group. Yet, it is unclear how the normalization of cannabis has impacted perceptions of stigma for older adults consuming cannabis medicinally. Qualitative description was used to elucidate the experiences of older Canadians aged 60+ related to stigma and their consumption of cannabis for medicinal purposes. Data collection involved semi-structured interviews. Data analysis examined how participants managed stigma related to cannabis use. Perceived stigma was evident in many participants' descriptions of their perceptions of cannabis in the past and present, and influenced how they accessed and consumed cannabis and their comfort in discussing its use with their healthcare providers. Participants employed several distinct strategies for managing stigma—concealing, re-framing, re-focusing, and proselytizing. Findings suggest that while medical cannabis consumption is becoming increasingly normalized among older adults, stigma related to cannabis persists and continues to shape older adults' experiences. A culture shift needs to occur among healthcare providers so that they are educated about cannabis and willing to discuss the possibilities of medicinal cannabis consumption with older adults. Otherwise, older adults may seek advice from recreational or other non-medical sources. Healthcare providers require education about the use of medical cannabis, so they can better advise older adults regarding its consumption for medicinal purposes. [ABSTRACT FROM AUTHOR]

Reproduction is a key feature of all organisms, yet the way in which it is achieved varies greatly across the tree of life. One striking example of this variation is the stick insect genus Bacillus , in which five different reproductive modes have been described: sex, facultative and obligate parthenogenesis, and two highly unusual reproductive modes: hybridogenesis and androgenesis. Under hybridogenesis, the entire genome from the paternal species is eliminated and replaced each generation by mating with the corresponding species. Under androgenesis, an egg is fertilized, but the developing diploid offspring bear two paternal genomes and no maternal genome, as a consequence of unknown mechanisms. Here, we reevaluate the previous descriptions of Bacillus lineages and the proposed F1 hybrid ancestries of the hybridogenetic and obligately parthenogenetic lineages (based on allozymes and karyotypes) from Sicily, where all these reproductive modes are found. We generate a chromosome-level genome assembly for a facultative parthenogenetic species (B. rossius) and combine extensive field sampling with RADseq and mtDNA data. We identify and genetically corroborate all previously described species and confirm the ancestry of hybrid lineages. All hybrid lineages have fully retained their F1 hybrid constitution throughout the genome, indicating that the elimination of the paternal genome in hybridogens is always complete and that obligate parthenogenesis in Bacillus hybrid species is not associated with an erosion of heterozygosity as known in other hybrid asexuals. Our results provide a stepping stone toward understanding the transitions between reproductive modes and the proximate mechanisms of genome elimination. [ABSTRACT FROM AUTHOR]

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however, how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell-cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single-cell migration, which KMT2D inactivation promoted in synergy with PI 3-kinase activation. The combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function and the single-cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase. [ABSTRACT FROM AUTHOR]

Over the past several years, there has been ongoing dialog within our academic journals and the profession regarding the value of examining extreme, unconventional, or unsettling contexts in management research. These conversations have highlighted that perhaps more than ever, we as a society are facing unprecedented grand and perplexing challenges, and conducting research in unconventional or extreme settings can reveal complex dynamics or relationships that we may not understand otherwise. Less discussed, however, are methodological considerations for conducting research in unique contexts. As such, we aim to extend the explicit discussion of effective strategies for scholars who consider the perspectives and workplace realities of unusual or unconventional populations. We bring together a collection of reflective essays rooted in the authors' experiences of collecting data from extreme contexts or unusual samples. We highlight how these rich experiences in the field required the authors to modify or extend methodological conventions with the goal of guiding scholars pursuing research in similarly unconventional contexts. [ABSTRACT FROM AUTHOR]

Voyeurism violates dominant moral codes in many societies. Yet, for a number of businesses, including erotic webcam, reality television, slum tourism, and mixed martial arts, voyeurism is an important part of value creation. The success of such businesses that violate dominant moral codes raises questions about value creation that existing theory in management cannot adequately answer. To help advance our understanding, we theorize howbusinesses commercializing voyeurismcreate value for audiences. Conceptualizing voyeurism as a social practice, we identify two dimensions of voyeurism— authenticity and transgression—that help create value by generating desirable emotional responses that facilitate a distinctive experience for audiences. However, we further argue that these same dimensions can also hinder value creation by generating undesirable emotional responses that may lead audiences to disengage fromthe practice. Accordingly, we contend that businesses’ ability to deliver value to audiences hinges on effective emotional optimization—efforts to reduce undesirable emotional responses by dampening the authenticity or transgression in the voyeuristic practice, while reinforcing the associated desirable emotional responses. We contribute to the literature by advancing a novel theory of the commercialization of voyeuristic practice. In doing so, we also enrich our understanding of both authenticity and transgression. [ABSTRACT FROM AUTHOR]

The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions (CPIs). However, epidemic risk across wards is still poorly described. We measured CPIs directly using wearable sensors given to all present in a clinical ward over a 36-h period, across 15 wards in three hospitals in April-June 2020. Data were collected from 2114 participants and combined with a simple transmission model describing the arrival of a single index case to the ward to estimate the risk of an outbreak. Estimated epidemic risk ranged four-fold, from 0.12 secondary infections per day in an adult emergency to 0.49 per day in general paediatrics. The risk presented by an index case in a patient varied 20-fold across wards. Using simulation, we assessed the potential impact on outbreak risk of targeting the most connected individuals for prevention. We found that targeting those with the highest cumulative contact hours was most impactful (20% reduction for 5% of the population targeted), and on average resources were better spent targeting patients. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk. [ABSTRACT FROM AUTHOR]

Increasingly we are faced with broad societal challenges that encourage us to rethink existing institutions. Yet many people also want to preserve institutions they cherish. This tension points to the need for change that can erode or discontinue unsustainable or problematic aspects of institutions while also maintaining what is sacred and valued. In this paper we ask how can organizations deinstitutionalize taken-for-granted practices while also preserving the institution? We answer this question by exploring how Trout Unlimited deployed visual and discursive tactics to push out unsustainable catch-and-harvest fly fishing practices and insert new catch-and-release practices. Our primary theoretical contribution is a model of repair-focused deinstitutionalization, illustrating how custodians utilize three forms of work to respond to threats—mending, caring, and restoring—all with an eye on deinstitutionalization via repair rather than disruption. Importantly, we show how the construct of repair is multipurpose, not limited to maintenance strategies, but can also be a catalyst for change. In addition, we extend research on deinstitutionalization by presenting a multimodal approach that goes beyond discourse, with particular attention to visuality and show how different modalities present different affordances in longer-term repair efforts. [ABSTRACT FROM AUTHOR]

Scholars studying stigmatized, or "dirty work," occupations have tended to characterize people outside of the occupation as the stigmatizers and those within the occupation as social supports who buffer each other from stigma. We argue that this characterization discounts the unique ways stigmatization can take place within heterogeneous occupations and the challenges it raises for finding support from other occupational members. Based on a six-year qualitative study of the sex work occupation in Canada, we explore the internal dynamics of stigmatization in the occupation. Our analysis reveals that sex workers are not just the stigmatized but also the stigmatizers, as they elaborate, borrow, and adapt perceptions of stigma to rank and place each other into a stigma hierarchy. To avoid the risks of being stigmatized based on this hierarchy, sex workers engage in stealth organizing to find safe others within the occupation to provide social support. Thus the occupation is not a stigma-free safe haven for its workers. Instead, the occupation as a whole is characterized by dissension among its members. Their efforts to find social support lead to what we call bounded entitativity : a sense of being grouplike that is confined to small community groups within a broader occupational context of dissension. We found bounded entitativity to be associated with challenges for occupational members in undertaking social change efforts. [ABSTRACT FROM AUTHOR]

Some analyses of the third gravitational wave catalogue released by the LIGO-Virgo-KAGRA collaboration (LVK) suggest an excess of black holes around |$15\!-\!20 \, {\rm M}_{\odot }$|⁠. In order to investigate this feature, we introduce two flexible population models, a semiparametric one and a non-parametric one. Both make use of reversible jump Markov chain Monte-Carlo to optimise their complexity. We also illustrate how the latter can be used to efficiently perform model selection. Our parametric model broadly agrees with the fiducial analysis of the LVK, but finds a peak of events at slightly larger masses. Our non-parametric model shows this same displacement. Moreover, it also suggests the existence of an excess of black holes around |$20 \, {\rm M}_{\odot }$|⁠. We assess the robustness of this prediction by performing mock injections and running simplified hierarchical analyses on those (i.e. without selection effects and observational uncertainties). We estimate that such a feature might be due to statistical fluctuations, given the small number of events observed so far, with a 5 per cent probability. We estimate that with a few hundreds of observations, as expected for O4, our non-parametric model will be able to robustly determine the presence of this excess. It will then allow for an efficient agnostic inference of the properties of black holes. [ABSTRACT FROM AUTHOR]

A rapidly growing research stream examines the social effects of entrepreneurship on society. This research assesses the rise of entrepreneurship as a dominant theme in society and studies how entrepreneurship contributes to the production and acceptance of socio-economic inequality regimes, social problems, class and power struggles, and systemic inequities. In this article, scholars present new perspectives on an organizational sociology-inspired research agenda of entrepreneurial capitalism and detail the potential remedies to bound the unfettered expansion of a narrow conception of entrepreneurship. Taken together, the essays put forward four central provocations: 1) reform the study and pedagogy of entrepreneurship by bringing in the humanities; 2) examine entrepreneurship as a cultural phenomenon shaping society; 3) go beyond the dominant biases in entrepreneurship research and pedagogy; and 4) explore alternative models to entrepreneurial capitalism. More scholarly work scrutinizing the entrepreneurship–society nexus is urgently needed, and these essays provide generative arguments toward further developing this research agenda. [ABSTRACT FROM AUTHOR]

Entrepreneurs work not only in socially accepted and valued domains but also in highly contested, stigmatized industries. Despite the extreme constraints of working in stigmatized domains, entrepreneurs manage to thrive. The fact that entrepreneurs in these industries appear to overcome the constraints of stigma raises questions about the actual impacts of stigma on entrepreneurs and their ventures. Our qualitative study of entrepreneurs in the sex industry in Canada reveals that the many constraints faced by entrepreneurs in stigmatized industries also create opportunities. Actualizing such stigma-based opportunities loosens the constraints of stigma and enables entrepreneurs to experience structural, cognitive, and emotional emancipation. However, such emancipation is confined to the context, and thus threatened by interactions with those outside the industry. Based on our findings, we develop a model of entrepreneurial emancipation in stigmatized industries. [ABSTRACT FROM AUTHOR]

Clinical, epidemiologic, and microbiologic analyses revealed emergence of 26 cases of Corynebacterium diphtheriae species complex infections on Réunion Island, France, during 2015-2020. Isolates were genetically diverse, indicating circulation and local transmission of several diphtheria sublineages. Clinicians should remain aware of the risk for diphtheria and improve diagnostic methods and patient management. [ABSTRACT FROM AUTHOR]

Main conclusion: A multi-year study of perennial Z. dumosum shows a consistent seasonal pattern in the changes of petiole metabolism, involving mainly organic acids, polyols, phenylpropanoids, sulfate conjugates, and piperazines. GC–MS and UPLC–QTOF-MS-based metabolite profiling was performed on the petioles of the perennial desert shrub Zygophyllum dumosum Boiss (Zygophyllaceae). The petioles, which are physiologically functional throughout the year and, thus, exposed to seasonal rhythms, were collected every month for 3 years from their natural ecosystem on a southeast-facing slope. Results showed a clear multi-year pattern following seasonal successions, despite different climate conditions, i.e., rainy and drought years, throughout the research period. The metabolic pattern of change encompassed an increase in the central metabolites, including most polyols, e.g., stress-related D-pinitol, organic and sugar acids, and in the dominant specialized metabolites, which were tentatively identified as sulfate, flavonoid, and piperazine conjugates during the summer–autumn period, while significantly high levels of free amino acids were detected during the winter–spring period. In parallel, the levels of most sugars (including glucose and fructose) increased in the petioles at the flowering stage at the beginning of the spring, while most of the di- and tri-saccharides accumulated at the beginning of seed development (May–June). Analysis of the conserved seasonal metabolite pattern of change shows that metabolic events are mostly related to the stage of plant development and its interaction with the environment and less to environmental conditions per se. [ABSTRACT FROM AUTHOR]

We know that individuals' identities can become intertwined with institutions through processes of identification. But what happens when individuals need or desire to disentangle their identities from institutions after identification has taken place? In this paper, I examine previously incarcerated men's efforts to de-identify with the institutional logics associated with prison as they transition back into society. While past work has tended to characterize de-identification efforts as ultimately successful, I reveal how individuals can remain stuck in their identifications and experience identity paralysis. In doing so I add nuance to our understanding of de-identification by revealing the factors that can contribute to its breakdown and failure. I highlight specifically the importance of identity material and the content of institutional logics in influencing de-identification processes, and thus extend the existing focus on the cognitive accessibility of logics. Importantly, I reveal that challenges to de-identification result not merely from the individuals "holding on" to old targets but rather from their becoming stuck and resigning themselves to existing targets when they simultaneously feel they lack identity material to realize new identities and face negative social evaluations. Indeed my findings point to the powerful and durable ways in which institutions shape our identities even when we desire to change them. [ABSTRACT FROM AUTHOR]

Introduction: Older Canadians (age 60+) are increasingly using cannabis to treat their health problems, but little is known regarding how they learn about medicinal cannabis. This study explored the perspectives of older cannabis consumers, prospective consumers, healthcare professionals, and cannabis retailers on older adults' information-seeking behavior and unmet knowledge needs. Methods: A qualitative descriptive design was used. Semi-structured telephone interviews were conducted with a purposeful sample of 36 older cannabis consumers and prospective consumers, as well as 4 healthcare professionals and 5 cannabis retailers from across Canada, for a total sample of 45 participants. Data were thematically analyzed. Results: Three main themes characterizing older cannabis consumers' information-seeking were identified: (1) knowledge sources, (2) types of information sought, and (3) unmet knowledge needs. Participants accessed a variety of knowledge sources to inform themselves about medicinal cannabis. Cannabis retailers were identified as providing medical information to many older adults, despite regulations to the contrary. Cannabis-specialized healthcare professionals were also viewed as key knowledge sources, while primary care providers were perceived as both knowledge sources and gatekeepers limiting access to information. The types of information participants sought included the effects and potential benefits of medicinal cannabis, the side effects and risks involved, and guidance regarding suitable cannabis products. Participants' most salient unmet knowledge needs focused on dosing and use of cannabis to treat specific health conditions. Discussion: Findings suggest that barriers to learning about medical cannabis among older consumers identified in prior research remain pervasive and cut across jurisdictions. To address these barriers, there is a need for better knowledge products tailored to older cannabis consumers and their information needs, and further education for primary healthcare providers on medicinal cannabis and its therapeutic applications with older patients. [ABSTRACT FROM AUTHOR]

The next generation of detectors will detect gravitational waves from binary neutron stars at cosmological distances, for which around a 1000 electromagnetic follow-ups may be observed per year. So far, most work devoted to the expected cosmological impact of these standard sirens employed them only as distance indicators. Only recently their use as tracers of clustering, similar to what already proposed for supernovae, has been studied. Focusing on the expected specifications of the Einstein Telescope (ET), we forecast here the performance on cosmological parameters of future standard sirens as both distance and density indicators, with emphasis on the linear perturbation growth index and on spatial curvature. We improve upon previous studies in a number of ways: a more detailed analysis of available telescope time, the inclusion of more cosmological and nuisance parameters, the Alcock–Paczynski correction, the use of sirens also as both velocity and density tracers, and a more accurate estimation of the distance posterior. We find that the analysis of the clustering of sirens improves the constraints on H 0 by 30 per cent and on Ω k 0 by over an order of magnitude, with respect to their use merely as distance indicators. With 5 yr of joint ET and Rubin Observatory follow-ups we could reach precision of 0.1 km s−1 Mpc−1 in H 0 and 0.02 in Ω k 0 using only data in the range 0 < z < 0.5. We also find that the use of sirens as tracers of density, and not only velocity, yields good improvements on the growth of structure constraints. [ABSTRACT FROM AUTHOR]

Changes in climate conditions can negatively affect the productivity of crop plants. They can induce chloroplast degradation (senescence), which leads to decreased source capacity, as well as decreased whole-plant carbon/nitrogen assimilation and allocation. The importance, contribution and mechanisms of action regulating source-tissue capacity under stress conditions in tomato (Solanum lycopersicum) are not well understood. We hypothesized that delaying chloroplast degradation by altering the activity of the tomato chloroplast vesiculation (CV) under stress would lead to more efficient use of carbon and nitrogen and to higher yields. Tomato CV is upregulated under stress conditions. Specific induction of CV in leaves at the fruit development stage resulted in stress-induced senescence and negatively affected fruit yield, without any positive effects on fruit quality. Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/CAS9) knockout CV plants, generated using a near-isogenic tomato line with enhanced sink capacity, exhibited stress tolerance at both the vegetative and the reproductive stages, leading to enhanced fruit quantity, quality and harvest index. Detailed metabolic and transcriptomic network analysis of sink tissue revealed that the l -glutamine and l -arginine biosynthesis pathways are associated with stress-response conditions and also identified putative novel genes involved in tomato fruit quality under stress. Our results are the first to demonstrate the feasibility of delayed stress-induced senescence as a stress-tolerance trait in a fleshy fruit crop, to highlight the involvement of the CV pathway in the regulation of source strength under stress and to identify genes and metabolic pathways involved in increased tomato sink capacity under stress conditions. [ABSTRACT FROM AUTHOR]

Background and Objective: We aimed to develop a meropenem population pharmacokinetic model in critically ill children receiving continuous renal replacement therapy and simulate dosing regimens to optimize patient exposure. Methods: Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem pharmacokinetics was investigated using a non-linear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration, according to the target of a 100% inter-dose interval time in which concentration is one to four times above the minimum inhibitory concentration (100% fT>1–4×MIC). Results: A total of 27 patients with a median age of 4 [interquartile range 0–11] years, a median body weight of 16 [range 7–35] kg receiving continuous renal replacement therapy were included. Concentration–time courses were best described by a one-compartment model with first-order elimination. Body weight (BW) produced significant effects on volume of distribution (V) and BW and continuous renal replacement therapy effluent flow rate (Qeff) produced significant effects on clearance (CL): V i = V pop x (BWi 70) 1 and CL i = CL pop x ( BWi 70) 0.75 x ( Qeffi 1200) 0.337 , where Vpop and CLpop estimates were 32.5 L and 5.88 L/h, respectively, normalized to a 70-kg BW and median Qeff at 1200 mL/h. Using this final model and Monte Carlo simulations, for patients with Qeff over 1200 mL/h, meropenem continuous infusion was adequate in most cases to attain 100% fT>1–4xMIC. For bacterial infections with a low minimum inhibitory concentration (≤2 mg/L), meropenem intermitent administration was appropriate for patients weighing more than 20 kg with Qeff <500 mL/h and for patients weighing more than 10 kg with Qeff <100 mL/h. Conclusions: Meropenem exposure in critically ill children receiving continuous renal replacement therapy needs dosing adjustments to the minimum inhibitory concentration that take into account body weight and the continuous renal replacement therapy effluent flow rate. [ABSTRACT FROM AUTHOR]

Semiaquatic bugs (Hemiptera: Heteroptera: Gerromorpha) are predatory insects that occupy a wide range of freshwater and marine habitats, with some secondary transitions to terrestrial life. They currently represent more than 2100 species distributed through all continents, except for Antarctica, and are especially rich in the Neotropical and Oriental regions. Although the fauna from the former region is relatively well known, some areas remain almost unexplored. Such is the case of French Guiana, where only a few species have been previously recorded, several of which based on collections made in the 19th and early 20th centuries. As a result of material recently collected in the territory, the descriptions of Rhagovelia depressa Rodrigues, Khila & Moreira, sp. nov., R. tantilloides Rodrigues, Khila & Moreira, sp. nov. and Steinovelia vittata Rodrigues, Khila & Moreira, sp. nov. (Veliidae) are presented here. New records for 28 species are also provided, of which Cylindrostethus hungerfordi Drake & Harris, 1934, Neogerris magnus (Kuitert, 1942), Rheumatobates mangrovensis (China, 1943), R. trinitatis (China, 1943), Ovatametra obesa Kenaga, 1942, Telmatometra fusca Kenaga, 1941, T. parva Kenaga, 1941 (Gerridae), Mesovelia amoena Uhler, 1894 (Mesoveliidae), Rhagovelia brunae Magalhães & Moreira, 2016, R. elegans Uhler, 1894, R. ephydros (Drake & Van Doesburg, 1966), R. equatoria D. Polhemus, 1997, R. evidis Bacon, 1948, R. guianana D. Polhemus, 1997, R. tenuipes Champion, 1898, Oiovelia cunucunumana (Drake & Maldonado-Capriles, 1952), Stridulivelia alia (Drake, 1957), S. stridulata (Hungerford, 1929), and S. tersa (Drake & Harris, 1941) (Veliidae) are reported from French Guiana for the first time. [ABSTRACT FROM AUTHOR]

Among the main metabolic pathways implicated in cancer cell proliferation are those of cholesterol and fatty acid synthesis, both of which are tightly regulated by sterol regulatory element-binding proteins (SREBPs). SREBPs are activated through specific cleavage by membrane-bound transcription factor protease 1 (MBTPS1), a serine protease that cleaves additional substrates (ATF6, BDNF, CREBs and somatostatin), some of which are also implicated in cell proliferation. The goal of this study was to determine whether MBTPS1 may serve as a master regulator in proliferation of colorectal cancer (CRC). Tumors from CRC patients showed variable levels of MBTPS1 mRNA, which were in positive correlation with the levels of SREBPs and ATF6, and in reverse correlation with BDNF levels. Chemical inhibition of MBTPS1 activity in two CRC-derived cell lines resulted in a marked decrease in the levels of SREBPs, but not of its other substrates and a marked decrease in cell proliferation, which suggested that MBTPS1 activity is critical for proliferation of these cells. In accordance, CRISPR/Cas9 targeted knockout (KO) of the MBTPS1 gene resulted in the survival of only a single clone that presented a phenotype of severely attenuated proliferation and marked downregulation of several energy metabolism pathways. We further showed that survival of the MBTPS1 KO clone was dependent upon significant upregulation of the type-1 interferon pathway, the inhibition of which halted proliferation entirely. Finally, rescue of the MBTPS1 KO cells, resulted in partial restoration of MBTPS1 levels, which was in accordance with partial recovery in proliferation and in SREBP levels. These finding suggest that MBTPS1 plays a critical role in regulating colon cancer proliferation primarily through SREBP-associated lipid metabolism, and as such may serve as a possible therapeutic target in CRC. [ABSTRACT FROM AUTHOR]

The present work focuses on the application of density-based topology optimization to the design of a surface cooler. This kind of device is used to cool down the oil circuit in aircraft engines thanks to the cold air in the bypass stream, and is subject to severe heat duty and pressure drop requirements. The optimization is carried out with an in-house implementation of the density method in OpenFOAM. A continuous adjoint strategy is employed to compute the sensitivities with respect to the design variables. Avoiding the so-called “frozen turbulence” assumption, the variations of the turbulent viscosity are taken into account in the computation of the sensitivity. The proposed model also considers the influence of the design variables on the wall distance function occurring in the formulation of the Spalart–Allmaras turbulence model. A simplified two-dimensional model is first employed to tune the optimization and the density model parameters. Then, the methodology is applied to a large-scale three-dimensional case, and the results are compared to a reference straight-fin geometry. The performance is finally evaluated with a reference solver, showing that the density model overestimates both the heat exchange and the total pressure loss, but that the methodology is still able to provide efficient designs in turbulent flow, starting from a very remote initialization. [ABSTRACT FROM AUTHOR]

Regulators of TLRs signaling pathways play an important role in the control of the pro-inflammatory response that contributes to sepsis-induced tissue injury. Mycophenolate mofetil, an immunosuppressive drug inhibiting lymphocyte proliferation, has been reported to be a regulator of TLRs signaling pathways. Whether MMF used at infra-immunosuppressive doses has an impact on survival and on innate immune response in sepsis is unknown. C57BL/6J mice were infected intraperitoneally with 108 CFU Staphylococcus aureus, and treated or not with low-dose of MMF (20mg/kg/day during 4 days). Survival rate and bacterial clearance were compared. Cytokine levels, quantitative and qualitative cellular responses were assessed. S. aureus -- infected mice treated with MMF exhibited improved survival compared to non-treated ones (48% vs 10%, p<0.001). With the dose used for all experiments, MMF did not show any effect on lymphocyte proliferation. MMF treatment also improved local and systemic bacterial clearance, improved phagocytosis activity of peritoneal macrophages resulting in decreased inflammatory cytokines secretion. MMF-treated mice showed enhanced activation of NF-κB seemed with a suspected TLR4-dependent mechanism. These results suggest that infra-immunosuppressive doses of MMF improve host defense during S. aureus sepsis and protects infected mice from fatal outcome by regulating innate immune responses. The signaling pathways involved could be TLR4-dependent. This work brings new perspectives in pathogenesis and therapeutic approaches of severe infections. [ABSTRACT FROM AUTHOR]

Regulators of TLRs signaling pathways play an important role in the control of the pro-inflammatory response that contributes to sepsis-induced tissue injury. Mycophenolate mofetil, an immunosuppressive drug inhibiting lymphocyte proliferation, has been reported to be a regulator of TLRs signaling pathways. Whether MMF used at infra-immunosuppressive doses has an impact on survival and on innate immune response in sepsis is unknown. C57BL/6J mice were infected intraperitoneally with 108 CFU Staphylococcus aureus, and treated or not with low-dose of MMF (20mg/kg/day during 4 days). Survival rate and bacterial clearance were compared. Cytokine levels, quantitative and qualitative cellular responses were assessed. S. aureus - infected mice treated with MMF exhibited improved survival compared to non-treated ones (48% vs 10%, p<0.001). With the dose used for all experiments, MMF did not show any effect on lymphocyte proliferation. MMF treatment also improved local and systemic bacterial clearance, improved phagocytosis activity of peritoneal macrophages resulting in decreased inflammatory cytokines secretion. MMF-treated mice showed enhanced activation of NF-κB seemed with a suspected TLR4-dependent mechanism. These results suggest that infra-immunosuppressive doses of MMF improve host defense during S. aureus sepsis and protects infected mice from fatal outcome by regulating innate immune responses. The signaling pathways involved could be TLR4-dependent. This work brings new perspectives in pathogenesis and therapeutic approaches of severe infections. [ABSTRACT FROM AUTHOR]

The genus Bordetella includes bacteria that are found in the environment and/or associated with humans and other animals. A few closely related species, including Bordetella pertussis, are human pathogens that cause diseases such as whooping cough. Here, we present a large database of Bordetella isolates and genomes and develop genotyping systems for the genus and for the B. pertussis clade. To generate the database, we merge previously existing databases from Oxford University and Institut Pasteur, import genomes from public repositories, and add 83 newly sequenced B. bronchiseptica genomes. The public database currently includes 2582 Bordetella isolates and their provenance data, and 2085 genomes (https://bigsdb.pasteur.fr/bordetella/). We use core-genome multilocus sequence typing (cgMLST) to develop genotyping systems for the whole genus and for B. pertussis, as well as specific schemes to define antigenic, virulence and macrolide resistance profiles. Phylogenetic analyses allow us to redefine evolutionary relationships among known Bordetella species, and to propose potential new species. Our database provides an expandable resource for genotyping of environmental and clinical Bordetella isolates, thus facilitating evolutionary and epidemiological research on whooping cough and other Bordetella infections. The genus Bordetella includes environmental bacteria as well as human pathogens. Here, the authors present a large database of environmental and clinical Bordetella isolates and genome sequences, and develop genotyping systems to facilitate evolutionary and epidemiological studies. [ABSTRACT FROM AUTHOR]

The article offers comments on the article "The Heart of Institutions: Emotional Competence and Institutional Actorhood" by M. Voronov and K. Weber in volume 41 of the journal. Topics include the concepts of emotional competence and emotional investment, the notion of an ethos in relation to institutional theory, and the relation of emotions to institutional norms.

In this paper, we explore how emotions influence organizations in situations of institutional complexity. In particular, we study members' and leaders' emotive responses and influence activities in response to a disruptive event that led to a violation of expectations. Our findings show that when people's expectations of an organization's actions are violated it can trigger a process of emotional escalation that leads to destabilization of the organization through the emotion-laden influence activities of shaming and shunning. The violation in our case resulted in strong negative emotions expressed on Facebook. Facebook acted as an emotional echo chamber where negative emotions were amplified and led to members' emotion-driven influence activities, eventually triggering regret and adaptation by the organization. We discuss implications for the study of emotions in institutional dynamics. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme. Methods: Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC0-24 h/MIC ratio ≥ 125. Results: A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance. Conclusion: The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC0-24 h to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m2) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually. [ABSTRACT FROM AUTHOR]

Electronic cigarettes are increasingly being used as smoking cessation aids. Most studies assess the dual use of e-cigarettes and traditional cigarettes, but there remains a paucity of literature concerning individuals who use e-cigarettes exclusively. Objective: The aim of this study is to examine the sociodemographic and clinical characteristics of exclusive e-cigarette users, and consider their willingness to quit e-cigarette use. Methods: A French online survey was conducted from March to December 2017. We assessed the following factors: sociodemographic factors; the clinical characteristics of e-cigarette use and its social acceptability; and the self-perceived effectiveness of nicotine replacement therapy (NRT). Associations between the listed factors and a willingness to quit e-cigarette use were examined. Results: A total of 386 exclusive e-cigarette users (70% men) participated in the study and were included in the analysis. Most respondents were not planning to quit e-cigarette use (75%). Compared to those who did not want to quit, a desire to quit was associated with using smoking cessation services (OR [95%CI]: 3.45 [1.82–6.56]), e-cigarette craving (OR [95%CI]: 2.63 [1.44–4.80]) and NRT past-use (1.78 [1.12–2.87]). Users who planned to quit expressed more concerns about smoking initiation among youths using e-cigarettes (OR [95%CI]: 3.62 [1.90–6.93]). In multivariate analysis, these associations remained significant for the use of smoking cessation services, e-cigarette cravings, and concerns about youth tobacco initiation. Conclusion: Most exclusive e-cigarette users were not likely to quit. Planned cessation was associated with using smoking cessation services, experiencing e-cigarette dependence symptoms, and being concerned about smoking initiation among teenager e-cigarette users. [ABSTRACT FROM AUTHOR]

Since the beginning of the COVID-19 pandemic, other respiratory illnesses decreased worldwide. This study described the consequences of public health measures on respiratory syncytial virus (RSV) severe infections in France, where an interseasonal resurgence of RSV occurred recently. All patients admitted to Necker Hospital (Paris) between August 2018 and April 2021 with a diagnosis of RSV-associated acute lung respiratory infection (ALRI) were enrolled. Characteristics of subjects with RSV-associated ALRI in 2020/2021 were compared to those infected during the two previous outbreaks. Overall, 664 inpatients were diagnosed with RSV-associated ALRI: 229, 183, and 252 during the 2018/2019, 2019/2020, and 2020/2021 outbreaks, respectively. During autumn 2020, a national lockdown began in France but schools remained open. A 3-month delayed RSV epidemic occurred at the end of this lockdown. Compared to previous outbreaks, the 2020/2021 epidemics involved more children aged 6 to 11 months (25.8% versus 13.1%, p < 0.0001), but less infants aged < 6 months (41.3% versus 56.6%, p < 0.0001) and less adults (0.0 versus 2.7%, p < 0.0001). Shorter length of stay at hospital, less frequent requirement of admission to intensive care unit, use of non-invasive ventilation, and/or high-flow nasal oxygen were observed in 2020/2021 than during previous epidemics (p < 0.0001). Delayed RSV outbreak was associated with more hospitalizations for ALRI, higher age of pediatric inpatients, but milder median clinical phenotype. Reinforced public health measures (even while keeping nurseries and schools open with mandatory face masks since six years of age) could impact, at least transiently, the burden of RSV-related hospitalizations. [ABSTRACT FROM AUTHOR]

A highly frequented beach in Marseille, France, was monitored on an hourly basis during a summer day in July 2018, to determine possible water and sand fecal pollution, in parallel with influx of beach users from 8 a.m. to 8 p.m. Fecal indicator bacteria were enumerated, together with four host-associated fecal molecular markers selected to discriminate human, dog, horse, or gull/seagull origins of the contamination. The antimicrobial resistance of bacteria in water and sand was evaluated by quantifying (i) the class 1, 2, and 3 integron integrase genes intI , and (ii) bla TEM, bla CTX–M, and bla SHV genes encoding endemic beta-lactamase enzymes. The number of beach users entering and leaving per hour during the observation period was manually counted. Photographs of the beach and the bathing area were taken every hour and used to count the number of persons in the water and on the sand, using a photo-interpretation method. The number of beach users increased from early morning to a peak by mid-afternoon, totaling more than 1,800, a very large number of users for such a small beach (less than 1 ha). An increase in fecal contamination in the water corresponded to the increase in beach attendance and number of bathers, with maximum numbers observed in the mid-afternoon. The human-specific fecal molecular marker HF183 indicated the contamination was of human origin. In the water, the load of Intl 2 and 3 genes was lower than Intl 1 but these genes were detected only during peak attendance and highest fecal contamination. The dynamics of the genes encoding B-lactamases involved in B-lactams resistance notably was linked to beach attendance and human fecal contamination. Fecal indicator bacteria, integron integrase genes intI , and genes encoding B-lactamases were detected in the sand. This study shows that bathers and beach users can be significant contributors to contamination of seawater and beach sand with bacteria of fecal origin and with bacteria carrying integron-integrase genes and beta lactamase encoding genes. High influx of users to beaches is a significant factor to be considered in order to reduce contamination and manage public health risk. [ABSTRACT FROM AUTHOR]

In this article, we take stock of the institutional logics perspective and highlight opportunities for new scholarship. While we celebrate the growth and generativity of the literature on institutional logics, we also note that there has been a troubling tendency in recent work to use logics as analytical tools, feeding disquiet about reification and reductionism. Seeding a broader scholarly agenda that addresses such weaknesses in the literature, we highlight nascent efforts that aim to more systematically understand institutional logics as complex, dynamic phenomena in their own right. In doing so, we argue for more research that probes how logics cohere and endure by unpacking the role of values, the centrality of practice, and the governance dynamics of institutional logics and their orders. Furthermore, we encourage bridging the study of institutional logics with various literatures, including ethnomethodology, phenomenology, professions, elites, world society, and the old institutionalism, to enhance progress in these directions. [ABSTRACT FROM AUTHOR]

Reported incidence of pertussis in the European Union (EU) and the European Economic Area (EEA) varies and may not reflect the real situation, while vaccine-induced protection against diphtheria and tetanus seems sufficient. We aimed to determine the seroprevalence of DTP antibodies in EU/EEA countries within the age groups of 40–49 and 50–59 years. Eighteen countries collected around 500 samples between 2015 and 2018 (N = 10,302) which were analysed for IgG-DTP specific antibodies. The proportion of sera with pertussis toxin antibody levels ≥100 IU/mL, indicative of recent exposure to pertussis was comparable for 13/18 countries, ranging between 2.7–5.8%. For diphtheria the proportion of sera lacking the protective level (<0.1 IU/mL) varied between 22.8–82.0%. For tetanus the protection was sufficient. Here, we report that the seroprevalence of pertussis in these age groups indicates circulation of B. pertussis across EU/EEA while the lack of vaccine-induced seroprotection against diphtheria is of concern and deserves further attention. Recent outbreaks of pertussis have highlighted the importance of surveillance of vaccine-preventable diseases. Here, the authors performed a cross-sectional seroprevalence study of pertussis, diphtheria, and tetanus in Europe and found evidence of circulation of pertussis in middle-aged adults. [ABSTRACT FROM AUTHOR]