Search

Abstract The MoEDAL’s Apparatus for Penetrating Particles (MAPP) Experiment is designed to expand the search for new physics at the LHC, significantly extending the physics program of the baseline MoEDAL Experiment. The Phase-1 MAPP detector (MAPP-1) is currently undergoing installation at the LHC’s UA83 gallery adjacent to the LHCb/MoEDAL region at Interaction Point 8 and will begin data-taking in early 2024. The focus of the MAPP experiment is on the quest for new feebly interacting particles — avatars of new physics with extremely small Standard Model couplings, such as minicharged particles (mCPs). In this study, we present the results of a comprehensive analysis of MAPP-1’s sensitivity to mCPs arising in the canonical model involving the kinetic mixing of a massless dark U(1) gauge field with the Standard Model hypercharge gauge field. We focus on several dominant production mechanisms of mCPs at the LHC across the mass-mixing parameter space of interest to MAPP: Drell-Yan pair production, direct decays of heavy quarkonia and light vector mesons, and single Dalitz decays of pseudoscalar mesons. The 95% confidence level background-free sensitivity of MAPP-1 for mCPs produced at the LHC’s Run 3 and the HL-LHC through these mechanisms, along with projected constraints on the minicharged strongly interacting dark matter window, are reported. Our results indicate that MAPP-1 exhibits sensitivity to sizable regions of unconstrained parameter space and can probe effective charges as low as 8 × 10 −4 e and 6 × 10 −4 e for Run 3 and the HL-LHC, respectively.

Abstract Background Estimating rates of disease importation by travellers is a key activity to assess both the risk to a country from an infectious disease emerging elsewhere in the world and the effectiveness of border measures. We describe a model used to estimate the number of travellers infected with SARS-CoV-2 into Canadian airports in 2021, and assess the impact of pre-departure testing requirements on importation risk. Methods A mathematical model estimated the number of essential and non-essential air travellers infected with SARS-CoV-2, with the latter requiring a negative pre-departure test result. The number of travellers arriving infected (i.e. imported cases) depended on air travel volumes, SARS-CoV-2 exposure risk in the departure country, prior infection or vaccine acquired immunity, and, for non-essential travellers, screening from pre-departure molecular testing. Importation risk was estimated weekly from July to November 2021 as the number of imported cases and percent positivity (PP; i.e. imported cases normalised by travel volume). The impact of pre-departure testing was assessed by comparing three scenarios: baseline (pre-departure testing of all non-essential travellers; most probable importation risk given the pre-departure testing requirements), counterfactual scenario 1 (no pre-departure testing of fully vaccinated non-essential travellers), and counterfactual scenario 2 (no pre-departure testing of non-essential travellers). Results In the baseline scenario, weekly imported cases and PP varied over time, ranging from 145 to 539 cases and 0.15 to 0.28%, respectively. Most cases arrived from the USA, Mexico, the United Kingdom, and France. While modelling suggested that essential travellers had a higher weekly PP (0.37 – 0.65%) than non-essential travellers (0.12 – 0.24%), they contributed fewer weekly cases (62 – 154) than non-essential travellers (84 – 398 per week) given their lower travel volume. Pre-departure testing was estimated to reduce imported cases by one third (counterfactual scenario 1) to one half (counterfactual scenario 2). Conclusions The model results highlighted the weekly variation in importation by traveller group (e.g., reason for travel and country of departure) and enabled a framework for measuring the impact of pre-departure testing requirements. Quantifying the contributors of importation risk through mathematical simulation can support the design of appropriate public health policy on border measures.

This research recounts a scholarship of teaching and learning (SoTL) project aimed at facilitating students’ empathic development while also offering ways to identify and assess students’ written expressions of empathy. I ground this work in an exploration of the many processes labelled as empathy and the reasons for including empathy as a course learning outcome. While participating in the Lighted School House program, I explored using progressive, or stacked, writing reflections to help students build, recognize, and articulate their own empathy. I conducted a close reading of final reflection papers in two offerings of a second-year community engagement course (in 2017 and 2019) in which students worked with an afterschool program in local elementary and middle schools. This enabled me to identify features of student writing—the evidence or “artifacts”— that illustrated their understanding of empathy, others’ perspectives, and positionality. To assess the depth and complexity with which students articulated their empathy, I devised a scale to identify these written expressions as novice, intermediate, or advanced. The analysis showed the importance of using an “imagine-other” perspective rather than merely imagining oneself in another’s situation, valuing others to inspire empathic action, and using conversation as a powerful tool for developing empathy. The project points to pedagogical practices that encourage students to employ effective conversation and listening skills in community engagement. This research suggests ways to help students better express their empathy by revising prompts and rubrics to clarify the particular empathic processes targeted and to foster strong writing skills.

Objective Guidelines recommend deprescribing benzodiazepine receptor agonists (BZRA) in older adults, yet implementation in clinical practice remains limited. Adapting effective, evidence-based interventions to a new context is a resource-saving strategy. In Canada, the D-PRESCRIBE intervention comprised a patient educational brochure and a pharmaceutical opinion inviting physicians to revise BZRA prescribing and consider safer alternatives. Due to its effectiveness on BZRA deprescribing among Canadian older adults, we aimed to adapt the D-PRESCRIBE intervention to the Belgian community setting.Design Recommendations from the ADAPT guidance, that provides a systematic approach for adapting interventions to new contexts, were followed. We conducted a mixed-methods study that comprised (1) group discussions and cognitive interviews to assess the acceptability and need for adaptation of the intervention’s components and (2) a survey on the adapted pharmaceutical opinion. A research committee involving stakeholders’ representatives decided on the adaptations, respecting the core functions of both tools. Changes in intervention components were reported following the Model for Adaptation Design and Impact framework.Setting Belgian French-speaking community setting.Participants Six older adults (≥65 years), six general practitioners (GPs) and seven pharmacists participated in the group discussions or interviews. 46 GPs and 91 pharmacists responded to the survey.Results Participants welcomed the brochure positively. Still, some changes in the vocabulary, wording, photos and icons were made for several purposes including making the patient feel concerned about the brochure and softening the use of fear. The pharmaceutical opinion aroused mixed perceptions. Its name, layout and content were adapted to enhance its acceptability and fit with our healthcare system, practices and national guidelines. The survey highlighted several enablers and barriers to its use from the perspectives of GP and pharmacist.Conclusions The Canadian D-PRESCRIBE intervention was adapted to the Belgian setting following a thorough and transparent process. Its feasibility will be tested in a future pilot study (NCT:05929417).

BackgroundThe effectiveness of public health measures (PHMs) depends on population adherence. Social media were suggested as a tool to assess adherence, but representativeness and accuracy issues have been raised. ObjectiveThe objectives of this repeated cross-sectional study were to compare self-reported PHM adherence and sociodemographic characteristics between people who used Twitter (subsequently rebranded X) and people who did not use Twitter. MethodsRepeated Canada-wide web-based surveys were conducted every 14 days from September 2020 to March 2022. Weighted proportions were calculated for descriptive variables. Using Bayesian logistic regression models, we investigated associations between Twitter use, as well as opinions in tweets, and self-reported adherence with mask wearing and vaccination. ResultsData from 40,230 respondents were analyzed. As self-reported, Twitter was used by 20.6% (95% CI 20.1%-21.2%) of Canadians, of whom 29.9% (95% CI 28.6%-31.3%) tweeted about COVID-19. The sociodemographic characteristics differed across categories of Twitter use and opinions. Overall, 11% (95% CI 10.6%-11.3%) of Canadians reported poor adherence to mask-wearing, and 10.8% (95% CI 10.4%-11.2%) to vaccination. Twitter users who tweeted about COVID-19 reported poorer adherence to mask wearing than nonusers, which was modified by the age of the respondents and their geographical region (odds ratio [OR] 0.79, 95% Bayesian credibility interval [BCI] 0.18-1.69 to OR 4.83, 95% BCI 3.13-6.86). The odds of poor adherence to vaccination of Twitter users who tweeted about COVID-19 were greater than those of nonusers (OR 1.76, 95% BCI 1.48-2.07). English- and French-speaking Twitter users who tweeted critically of PHMs were more likely (OR 4.07, 95% BCI 3.38-4.80 and OR 7.31, 95% BCI 4.26-11.03, respectively) to report poor adherence to mask wearing than non–Twitter users, and those who tweeted in support were less likely (OR 0.47, 95% BCI 0.31-0.64 and OR 0.96, 95% BCI 0.18-2.33, respectively) to report poor adherence to mask wearing than non–Twitter users. The OR of poor adherence to vaccination for those tweeting critically about PHMs and for those tweeting in support of PHMs were 4.10 (95% BCI 3.40-4.85) and 0.20 (95% BCI 0.10-0.32), respectively, compared to non–Twitter users. ConclusionsOpinions shared on Twitter can be useful to public health authorities, as they are associated with adherence to PHMs. However, the sociodemographics of social media users do not represent the general population, calling for caution when using tweets to assess general population-level behaviors.

Objectives To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.Methods CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score – C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP

We generalize the U(1) gauge transformations of electrodynamics by means of an analytical extension of their parameter space and observe that this leads naturally to two gauge potentials, one electric, one magnetic, which permit the writing of local Lagrangians describing elementary particles with electric and magnetic charges. Gauge invariance requires a conformal transformation of the metric tensor. We apply this approach, which borrows from Utiyama’s methodology, to a model with a massless scalar field and a model with a massless spinor field. We observed that for spinor models non-symmetrized Lagrangians can enable the existence of magnetic monopoles, but this is not possible with symmetrized Lagrangian. Such restrictions do not occur for spinless fields, but the model does not allow spin-one fields interacting with monopoles.

This paper presents a pioneering approach for simulation of economic activity, policy implementation, and pricing of goods in token economies. The paper proposes a formal analysis framework for wealth distribution analysis and simulation of interactions between economic participants in an economy. Using this framework, we define a mechanism for identifying prices that achieve the desired wealth distribution according to some metric, and stability of economic dynamics. The motivation to study tokenomics theory is the increasing use of tokenization, specifically in financial infrastructures, where designing token economies is in the forefront. Tokenomics theory establishes a quantitative framework for wealth distribution amongst economic participants and implements the algorithmic regulatory controls mechanism that reacts to changes in economic conditions. In our framework, we introduce a concept of tokenomic taxonomy where agents in the economy are categorized into agent types and interactions between them. This novel approach is motivated by having a generalized model of the macroeconomy with controls being implemented through interactions and policies. The existence of such controls allows us to measure and readjust the wealth dynamics in the economy to suit the desired objectives.

Abstract We revisit the thermal production and annihilation of magnetic monopoles and their relic abundance in order to gain a deeper physical interpretation on the monopole phenomenology predicted from the Baines et al.’s effective field theory, recently proposed in the description of monopole pair production via Drell–Yan and photon fusion processes. In this sense, we use of the vacuum cross sections for the Drell–Yan reactions derived within the mentioned framework to evaluate the cross section averaged over the thermal distribution associated to other particles that constitute the hot medium where the monopoles propagate. In the considered range of monopole mass with spin-zero and spin-half, our findings suggest that the thermally averaged cross sections for the pair production are highly suppressed, while at higher temperatures those for the annihilation of lighter pairs reach larger magnitudes. Besides, we observe that smaller temperature leads to a rate of annihilation for scalar monopoles smaller than the one for fermionic monopoles, which might be interpreted as a theoretical evidence of a more pronounced stability for spin-zero and heavier monopoles. Then we input these thermally averaged cross sections into the kinetic equation that describes the evolution of the monopole abundance via an extension of a freeze-out theory. Our results infer that heavier monopoles achieve the equilibrium at earlier stages of the expansion, and consequently at higher temperatures. In addition, larger monopole masses produce higher values of the relic abundance. Besides, the results indicate that the abundance does not behave differently for spin-zero and spin-half relic monopoles.

The COVID-19 pandemic triggered unprecedented expansion of telemedicine, including in the delivery of opioid agonist treatment (OAT) for people with opioid use disorder (OUD). However, many people with OUD lack the technological resources necessary for remote care, have complex needs, and are underserved, with precarious access to mainstream services. To address the needs of these individuals, we devised a unique program to deliver OAT via telemedicine with the support of community outreach workers in Montreal (Quebec, Canada). The program was co-constructed by the service de médecine des toxicomanies of the Centre hospitalier de l’Université de Montréal (CHUM-SMT)—a hospital-based addiction medicine service—and CACTUS Montréal—a community-based harm reduction organization known and trusted by its clientele. All procedures were jointly developed to enable flexible and rapid appointment scheduling. CACTUS Montréal workers promoted the program, facilitated private on-site telemedicine connections to the CHUM-SMT, accompanied patients during web-based appointments if requested, and provided ongoing holistic support and follow-up. The CHUM-SMT offered individualized OAT regimens and other health services as needed. Overall, our experience as clinicians and community-based workers intimately involved in establishing and running this initiative suggests that participants found it to be convenient, nonjudgmental, and responsive to their needs, and that the implication of CACTUS Montréal was highly valued and integral to patient engagement and retention. Beyond the context of the COVID-19 pandemic, similar programs may present a flexible and accessible means to deliver alternative treatment options for people with OUD disengaged from traditional care, bridge gaps between communities and health providers, and improve access to care in rural or remote settings.

Marinas are semi-enclosed environments characterised by reduced hydrodynamic energy, high sedimentation rates, and reduced oxygen levels. The ongoing development of activities and infrastructure construction are leading to deterioration in the quality of coastal aquatic environments, creating environmental risks. Trace metal elements (TMEs) and organotins are significant contaminants, prompting this study to evaluate the added value of spatiotemporal monitoring compared to one-time sediment assessments. Two Mediterranean harbours, Port Camargue (PC) and Port Carnon (C), differing in morphology and size, were monitored for a year with regular water sampling, focusing on TMEs and organotins. Sediment contamination, notably in the technical zone, revealed concentrations of Cu (309 and 1210 mg kg−1 for C and PC, respectively), Zn (242 and 425 mg kg−1 for C and PC, respectively), and tributyltin (TBT) (198 and 4678 µg (Sn) kg−1 for C and PC, respectively) surpassing the effect range medium (ERM), while other marina stations generally stayed below this threshold. Spatiotemporal water monitoring highlighted concentrations above environmental quality standards (EQS) at all stations of the larger marina. This exceedance was systematic for Cu and Zn in all samples, ranging respectively between 2.54 and 37.56 µg (Sn) L−1 and 0.63 and 33.48 µg (Sn) L−1. A notable temporal dynamic for TBT and Cu was also observed. Conversely, the open marina, connected to the open sea, rarely exhibited concentrations above EQS in water, despite sediment concentrations occasionally exceeding ERM values. This underscores that risk assessment in these ecosystems cannot rely solely on sediment characterisation.

Abstract A search for highly electrically charged objects (HECOs) and magnetic monopoles is presented using 2.2 $$\hbox {fb}{^{-1}}$$ fb - 1 of $$p-p$$ p - p collision data taken at a centre of mass energy (E $$_{CM}$$ CM ) of 8 TeV by the MoEDAL detector during LHC’s Run-1. The data were collected using MoEDAL’s prototype Nuclear Track Detectord array and the Trapping Detector array. The results are interpreted in terms of Drell–Yan pair production of stable HECO and monopole pairs with three spin hypotheses (0, 1/2 and 1). The search provides constraints on the direct production of magnetic monopoles carrying one to four Dirac magnetic charges and with mass limits ranging from 590 GeV/c $$^{2}$$ 2 to 1 TeV/c $$^{2}$$ 2 . Additionally, mass limits are placed on HECOs with charge in the range 10e to 180e, where e is the charge of an electron, for masses between 30 GeV/c $$^{2}$$ 2 and 1 TeV/c $$^{2}$$ 2 .

Abstract Objectives: to describe the identification of fetal death during pregnancy in Brazilian and Canadian women. Methods: clinical-qualitative study with women who experienced the outcome of fetal death in their pregnancies, living in Maringá (Brazil) and participating in the Center d’intervention familiale (Canada). Data collection was performed through a semi-structured interview with the question: How did you find out about your baby’s death? Readings were performed and the relevant aspects were categorized into themes according to the places where the death was confirmed. Results: in both countries, the main causes of death were the same, related to complications in pregnancy and childbirth, and health problems of the pregnant woman or fetus. Brazilian women had a higher frequency of deaths in the third trimester and Canadian women experienceda majority of deaths in the second trimester. The stillbirthswere found in different places, times and moments categorized at prenatal routine consultation, emergency care, expected death from congenital malformations of poor prognosis and labor. Conclusions: the determination of fetal death during pregnancy was due to possible intrinsic intercurrences of the pregnancy period. Based on the women’s experiences, it was possible to demonstrate the clinical practice of identifying fetal death according to the cultural scenario. Continuous studies on prenatal care for women who had stillbirths are necessary for early detection of pathological conditions and appropriate interventions.

Research Framework: Childhood cancer relapse requires new meanings and new strategies for the family to cope with this phase. The way men deal with situations of childhood illness is influenced by social norms, beliefs, and cultural values. Therefore, medical anthropology and masculinities were chosen as theoretical frameworks of this study. Objectives: This article examines the experiences of fathers of children with cancer relapse. Methodology: Narrative research conducted with 13 Brazilian fathers. Data were collected through in-depth interviews, using a semi-structured script and then processed through inductive thematic analysis. Results: A thematic narrative synthesis was elaborated: “Good days, bad days: oscillating between the resignation of death and the hope of healing”. The news of the relapse in conjunction with the child’s signs of clinical worsening brought the fathers closer to the limits of treatment and the finitude of life, although they also presented with hope for a cure. As a result, fathers wavered between building emotion-centred strategies and adopting life-engaging behaviours and strategies. In addition to maintaining hope, fathers mobilized the following resources: religion, spirituality, and emotional and instrumental support. Conclusion: Culture, especially masculinities, influence and is influenced by fathers’ experiences throughout a child’s cancer relapse. Contribution: A better understanding of the particularities of men’s experiences facilitates the development of father-specific interventions. Palliative care can benefit fathers by helping them become aware of finitude and begin a process anticipatory mourning, which contributes to making sense of the experience and coming to terms with possible death.

Individual retinal cell types exhibit semi-regular spatial patterns called retinal mosaics. Retinal ganglion cells (RGCs) and starburst amacrine cells (SACs) are known to exhibit such layouts. Mechanisms responsible for the formation of mosaics are not well understood but follow three main principles: (i) homotypic cells prevent nearby cells from adopting the same type, (ii) cell tangential migration and (iii) cell death. Alongside experiments in mouse, we use BioDynaMo, an agent-based simulation framework, to build a detailed and mechanistic model of mosaic formation. We investigate the implications of the three theories for RGC's mosaic formation. We report that the cell migration mechanism yields the most regular mosaics. In addition, we propose that low-density RGC type mosaics exhibit on average low regularities, and thus we question the relevance of regular spacing as a criterion for a group of RGCs to form a RGC type. We investigate SAC mosaics formation and interactions between the ganglion cell layer (GCL) and inner nuclear layer (INL) populations. We propose that homotypic interactions between the GCL and INL populations during mosaics creation are required to reproduce the observed SAC mosaics' characteristics. This suggests that the GCL and INL populations of SACs might not be independent during retinal development.

Introduction to the proceedings of the 34th International Colloquium on Group Theoretical Methods in Physics.

We report on recent work concerning a new type of generalised Kac-Moody algebras based on the spaces of differentiable mappings from compact manifolds or homogeneous spaces onto compact Lie groups.

Background: Across the world, a growing number of couples are directly or indirectly affected by infertility. Advances in assisted reproductive technologies are now enabling many of them to plan to have a child. As pregnancies resulting from assisted reproductive technologies are being experienced by a growing number of couples, it is important to better understand their experiences and the difficulties they encounter during the prenatal period. Objective: This literature review aims to synthesize the qualitative results of primary studies in order to better understand couples’ experiences of pregnancy resulting from assisted reproductive technologies, after having experienced infertility. Design: A meta-synthesis was conducted in accordance with the guidelines put forth by Sandelowski and Barroso in order to carry out an integrative analysis of the knowledge resulting from qualitative studies on this phenomenon. Data sources: The literature search was carried out between October and November 2020. Seven electronic databases were searched (CINAHL, Medline, PsycNet, SCOPUS, ScienceDirect, CAIRN, ERUDIT) and 14 eligible articles were selected. Review methods: The data from the “results” and “findings” sections of each of the articles were synthesized through thematic analysis to examine and summarize the topics found in the articles selected and develop the main themes. Results: The thematic analysis is structured around four themes to describe and interpret different aspects of the experience of pregnancy resulting from ART, namely: 1) travelling a long and complex journey; 2) moving on with paradoxical emotions; 3) struggling with an emerging identity; and 4) reorganizing relationships. These results shed light on the complex issues faced by couples previously affected by infertility during a pregnancy resulting from assisted reproductive technologies. Conclusion: The journey of a pregnancy resulting from assisted reproductive technologies must be recognized in order to offer support in line with the challenges faced by couples. This research will allow for a deeper understanding of women's experience, as well as that of their partner's, in a more specific way, and to better understand the impact on family and loved ones.

Objectives: Ventilator-associated pneumonia (VAP) is a severe care-related disease. The Centers for Disease Control defined the diagnosis criteria; however, the pediatric criteria are mainly subjective and retrospective. Clinical decision support systems have recently been developed in healthcare to help the physician to be more accurate for the early detection of severe pathology. We aimed at developing a predictive model to provide early diagnosis of VAP at the bedside in a pediatric intensive care unit (PICU). Methods: We performed a retrospective single-center study at a tertiary-care pediatric teaching hospital. All patients treated by invasive mechanical ventilation between September 2013 and October 2019 were included. Data were collected in the PICU electronic medical record and high-resolution research database. Development of the clinical decision support was then performed using open-access R software (Version 3.6.1®). Measurements and main results: In total, 2077 children were mechanically ventilated. We identified 827 episodes with almost 48 h of mechanical invasive ventilation and 77 patients who suffered from at least one VAP event. We split our database at the patient level in a training set of 461 patients free of VAP and 45 patients with VAP and in a testing set of 199 patients free of VAP and 20 patients with VAP. The Imbalanced Random Forest model was considered as the best fit with an area under the ROC curve from fitting the Imbalanced Random Forest model on the testing set being 0.82 (95% CI: (0.71, 0.93)). An optimal threshold of 0.41 gave a sensitivity of 79.7% and a specificity of 72.7%, with a positive predictive value (PPV) of 9% and a negative predictive value of 99%, and with an accuracy of 79.5% (95% CI: (0.77, 0.82)). Conclusions: Using machine learning, we developed a clinical predictive algorithm based on clinical data stored prospectively in a database. The next step will be to implement the algorithm in PICUs to provide early, automatic detection of ventilator-associated pneumonia.

Abstract Objectives The introduction of a new technology has the potential to modify clinical practices, especially if easy to use, reliable and non-invasive. This observational before/after multicenter service evaluation compares fluid management practices during surgery (with fluids volumes as primary outcome), and clinical outcomes (secondary outcomes) before and after the introduction of the Pleth Variability Index (PVI), a non-invasive fluid responsiveness monitoring. Results In five centers, 23 anesthesiologists participated during a 2-years period. Eighty-eight procedures were included. Median fluid volumes infused during surgery were similar before and after PVI introduction (respectively, 1000 ml [interquartile range 25–75 [750–1700] and 1000 ml [750–2000]). The follow-up was complete for 60 from these and outcomes were similar. No detectable change in the fluid management was observed after the introduction of a new technology in low to moderate risk surgery. These results suggest that the introduction of a new technology should be associated with an implementation strategy if it is intended to be associated with changes in clinical practice.

Introduction Globally, the COVID-19 pandemic has significantly disrupted the provision of healthcare and efficiency of healthcare systems and is likely to have profound implications for pregnant and postpartum women and their families including those who experience the tragedy of stillbirth or neonatal death. This study aims to understand the psychosocial impact of COVID-19 and the experiences of parents who have accessed maternity, neonatal and bereavement care services during this time.Methods and analysis An international, cross-sectional, online and/or telephone-based/face-to-face survey is being administered across 15 countries and available in 11 languages. New, expectant and bereaved parents during the COVID-19 pandemic will be recruited. Validated psychometric scales will be used to measure psychosocial well-being. Data will be analysed descriptively and by assessing multivariable associations of the outcomes with explanatory factors. In seven of these countries, bereaved parents will be recruited to a nested, qualitative interview study. The data will be analysed using a grounded theory analysis (for each country) and thematic framework analysis (for intercountry comparison) to gain further insights into their experiences.Ethics and dissemination Ethics approval for the multicountry online survey, COCOON, has been granted by the Mater Misericordiae Human Research Ethics Committee in Australia (reference number: AM/MML/63526). Ethics approval for the nested qualitative interview study, PUDDLES, has been granted by the King’s College London Biomedical & Health Sciences, Dentistry, Medicine and Natural & Mathematical Sciences Research Ethics Subcommittee (reference number: HR-19/20-19455) in the UK. Local ethics committee approvals were granted in participating countries where required. Results of the study will be published in international peer-reviewed journals and through parent support organisations. Findings will contribute to our understanding of delivering maternity care services, particularly bereavement care, in high-income, lower middle-income and low-income countries during this or future health crises.

Abstract Background Recent genome-wide studies of many species reveal the existence of a myriad of RNAs differing in size, coding potential and function. Among these are the long non-coding RNAs, some of them producing functional small peptides via the translation of short ORFs. It now appears that any kind of RNA presumably has a potential to encode small peptides. Accordingly, our team recently discovered that plant primary transcripts of microRNAs (pri-miRs) produce small regulatory peptides (miPEPs) involved in auto-regulatory feedback loops enhancing their cognate microRNA expression which in turn controls plant development. Here we investigate whether this regulatory feedback loop is present in Drosophila melanogaster. Results We perform a survey of ribosome profiling data and reveal that many pri-miRNAs exhibit ribosome translation marks. Focusing on miR-8, we show that pri-miR-8 can produce a miPEP-8. Functional assays performed in Drosophila reveal that miPEP-8 affects development when overexpressed or knocked down. Combining genetic and molecular approaches as well as genome-wide transcriptomic analyses, we show that miR-8 expression is independent of miPEP-8 activity and that miPEP-8 acts in parallel to miR-8 to regulate the expression of hundreds of genes. Conclusion Taken together, these results reveal that several Drosophila pri-miRs exhibit translation potential. Contrasting with the mechanism described in plants, these data shed light on the function of yet undescribed primary-microRNA-encoded peptides in Drosophila and their regulatory potential on genome expression.

Abstract Sarcolipin (SLN), a single-spanning membrane protein, is a regulator of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA1a). Chemically synthesized SLN, palmitoylated or not (pSLN or SLN), and recombinant wild-type rabbit SERCA1a expressed in S. cerevisiae design experimental conditions that provide a deeper understanding of the functional role of SLN on the regulation of SERCA1a. Our data show that chemically synthesized SLN interacts with recombinant SERCA1a, with calcium-deprived E2 state as well as with calcium-bound E1 state. This interaction hampers the binding of calcium in agreement with published data. Unexpectedly, SLN has also an allosteric effect on SERCA1a transport activity by impairing the binding of ATP. Our results reveal that SLN significantly slows down the E2 to Ca2.E1 transition of SERCA1a while it affects neither phosphorylation nor dephosphorylation. Comparison with chemically synthesized SLN deprived of acylation demonstrates that palmitoylation is not necessary for either inhibition or association with SERCA1a. However, it has a small but statistically significant effect on SERCA1a phosphorylation when various ratios of SLN-SERCA1a or pSLN-SERCA1a are tested.

Gene targeting approaches have demonstrated the essential role for the malaria parasite of membrane transport proteins involved in lipid transport and in the maintenance of membrane lipid asymmetry, representing emerging oportunites for therapeutical intervention. This is the case of ATP2, a Plasmodium-encoded 4 P-type ATPase (P4-ATPase or lipid flippase), whose activity is completely irreplaceable during the asexual stages of the parasite. Moreover, a recent chemogenomic study has situated ATP2 as the possible target of two antimalarial drug candidates. In eukaryotes, P4-ATPases assure the asymmetric phospholipid distribution in membranes by translocating phospholipids from the outer to the inner leaflet. In this work, we have used a recombinantly-produced P. chabaudi ATP2 (PcATP2), to gain insights into the function and structural organization of this essential transporter. Our work demonstrates that PcATP2 associates with two of the three Plasmodium-encoded Cdc50 proteins: PcCdc50B and PcCdc50A. Purified PcATP2/PcCdc50B complex displays ATPase activity in the presence of either phosphatidylserine or phosphatidylethanolamine. In addition, this activity is upregulated by phosphatidylinositol 4-phosphate. Overall, our work describes the first biochemical characterization of a Plasmodium lipid flippase, a first step towards the understanding of the essential physiological role of this transporter and towards its validation as a potential antimalarial drug target.

Recent studies have shown that hundreds of small proteins were occulted when protein-coding genes were annotated. These proteins, called alternative proteins, have failed to be annotated notably due to the short length of their open reading frame (less than 100 codons) or the enforced rule establishing that messenger RNAs (mRNAs) are monocistronic. Several alternative proteins were shown to be biologically active molecules and seem to be involved in a wide range of biological functions. However, genome-wide exploration of the alternative proteome is still limited to a few species. In the present article, we describe a deep peptidomics workflow which enabled the identification of 401 alternative proteins in Drosophila melanogaster. Subcellular localization, protein domains, and short linear motifs were predicted for 235 of the alternative proteins identified and point toward specific functions of these small proteins. Several alternative proteins had approximated abundances higher than their canonical counterparts, suggesting that these alternative proteins are actually the main products of their corresponding genes. Finally, we observed 14 alternative proteins with developmentally regulated expression patterns and 10 induced upon the heat-shock treatment of embryos, demonstrating stage or stress-specific production of alternative proteins.

P4-ATPases flip lipids from the exoplasmic to the cytosolic leaflet, thus maintaining lipid asymmetry in eukaryotic cell membranes. Mutations in several human P4-ATPase genes are associated with severe diseases, for example in ATP8B1 causing progressive familial intrahepatic cholestasis, a rare inherited disorder progressing toward liver failure. ATP8B1 forms a binary complex with CDC50A and displays a broad specificity to glycerophospholipids, but regulatory mechanisms are unknown. Here, we report functional studies and the cryo-EM structure of the human lipid flippase ATP8B1-CDC50A at 3.1 Å resolution. We find that ATP8B1 is autoinhibited by its N- and C-terminal tails, which form extensive interactions with the catalytic sites and flexible domain interfaces. Consistently, ATP hydrolysis is unleashed by truncation of the C-terminus, but also requires phosphoinositides, most markedly phosphatidylinositol-3,4,5-phosphate (PI(3,4,5)P3), and removal of both N- and C-termini results in full activation. Restored inhibition of ATP8B1 truncation constructs with a synthetic peptide mimicking the C-terminal segment further suggests molecular communication between N- and C-termini in the autoinhibition and demonstrates that the regulatory mechanism can be interfered with by exogenous compounds. A recurring (G/A)(Y/F)AFS motif of the C-terminal segment suggests that this mechanism is employed widely across P4-ATPase lipid flippases in plasma membrane and endomembranes.

Introduction : Une grossesse sur cinq ne se rend pas à terme au Canada et ce type de perte est une expérience douloureuse pour les parents. Les chercheurs qui se sont intéressés au vécu de ces familles endeuillées décrivent des interventions à privilégier, mais en les généralisant à l’ensemble des populations touchées par ce phénomène. Or, l’expérience spécifique des parents immigrants est peu étudiée. Par conséquent, leurs besoins sont méconnus et les interventions de soutien et d’accompagnement à leur endroit sont peu développées et personnalisées. Objectifs : Cette étude vise à décrire l’expérience, à travers le parcours de soins, de parents immigrants ayant vécu un décès périnatal. En deuxième lieu, elle vise à décrire leurs besoins. Méthode : Une recherche de type qualitative descriptive, par l’entremise d’entretiens semi-dirigés, a permis de rencontrer 18 parents immigrants ayant vécu un décès périnatal dans les 5 dernières années et vivant dans 3 régions différentes du Québec (Canada). Résultats : L’analyse de leur expérience fait émerger 3 thèmes : une méconnaissance du réseau de la santé, l’importance des soins personnalisés et un isolement teinté par le parcours migratoire. Discussion et conclusion : L’expérience d’avoir vécu un décès périnatal comporte des spécificités propres à la communauté immigrante. Les parents issus de cette communauté vivent des défis plus marqués considérant le contexte d’immigration. Des recommandations cliniques simples pourraient permettre de reconnaître leur expérience particulière liée à leur vécu de parent immigrant. Il incombe de personnaliser les soins qui leur seront offerts.

We present an exploratory study carried out with a new miniature portable emission measurement system (Mini-PEMS) specifically designed at the Technical University of Liberec (CZ) for applications on two-wheeler vehicles owing to its reduced size (45cm×30×20cm) and weight (≈15 kg). It measures the exhaust gas concentrations of hydrocarbons and carbon mono- and dioxide with a nondispersive infrared method and nitrogen mono- and dioxides and oxygen using an electrochemical cell. In addition, the instrument acquires the engine speed, manifold absolute pressure, inlet and exhaust gas temperature, geo-localization, and vehicle speed. The exhaust mass flow rate is calculated from engine and emission data. The Mini-PEMS was validated on three two-wheelers (one moped and two motorcycles) against laboratory-grade instrumentation in the Vehicle Emissions Laboratory of the European Commission in terms of measured concentrations, exhaust flow, fuel consumption, and mass emission of pollutants. The mean absolute deviations of gas concentrations were 8 % for HC, 8 % for CO, 13 % for NOx, and 2 % for CO2, while the mass emissions (which include the exhaust flow determination uncertainty) were 7 % for HC, 7 % for CO, 9 % for NOx, and 5 % for CO2. An agreement of 2 % was achieved between the fuel consumption measured in the laboratory and calculated by the Mini-PEMS. As an application, the instrument was tested on board the vehicles during on-road trips. The emissions measured on the road were consistent among repeated runs, with differences between laboratory and on-road tests much larger than those between the Mini-PEMS and laboratory. We found similar or larger HC and NOx real-driving emissions and larger CO emissions from motorcycles and smaller ones for the moped. Considering its size and weight, the Mini-PEMS proved to be an efficient tool for vehicle monitoring, research and development and could be tested for in-service monitoring applications related to carbon monoxide and nitrogen oxides emissions. A tentative approach to characterize particulate mass and particle number was presented and compared to the existing filter method and nonvolatile particle number protocol.

Introduction: Miscarriage is common, occurring in nearly 20% of pregnancies. Most women experiencing symptoms such as bleeding or abdominal pain in early pregnancy consult emergency services, the front line of care. While research has shown the psychological and physical effects of miscarriage on women, less is known about how emergency services are organized to manage their care. Objective: To describe and analyze the organization of emergency services for women experiencing miscarriage. Methods: A multiple case study was conducted in four emergency rooms in Quebec, Canada, between 2014 and 2015. A reference framework setting out an organized system of action in care adapted to emergency services was used to analyze 198 medical records of women who experienced miscarriage and were treated in these emergency rooms. Results: From the analysis, observations were made regarding the accessibility, responsiveness, and productivity of emergency services, as well as deficiencies in care continuity. While medical treatments generally corresponded to standards, system responsiveness was poor, with long waits that may have added to women’s psychological distress. Gaps were observed in care continuity, effectiveness, and quality, including missing notes in charts, high readmission rates, and lack of referrals to relevant psychosocial and other support services. Discussion and conclusion: Recommendations include developing clinical guidelines, care trajectories, and checklists for nurses’ clinical assessments. As well, early pregnancy assessment clinics are an innovative care delivery model that has proven effective in reducing admissions, shortening hospitalizations, and providing comprehensive support services.

Abstract Background Approximately 50% of systemic lupus erythematosus (SLE) patients develop nephritis, which is among the most severe and frequent complications of the disease and a leading cause of morbidity and mortality. Despite intensive research, there are still no reliable lupus nephritis (LN) markers in clinical use that can assess renal damage and activity with a high sensitivity and specificity. To this end, the aim of this study was to identify new clinically relevant tissue-specific protein biomarkers and possible underlying molecular mechanisms associated with renal involvement in SLE, using mass spectrometry (MS)-based proteomics. Methods Kidneys were harvested from female triple congenic B6.NZMsle1/sle2/sle3 lupus mice model, and the respective sex- and age-matched C57BL/6 control mice at 12, 24 and 36 weeks of age, representing pre-symptomatic, established and end-stage LN, respectively. Proteins were extracted from kidneys, purified, reduced, alkylated and digested by trypsin. Purified peptides were separated by liquid chromatography and analysed by high-resolution MS. Data were processed by the Progenesis QIp software, and functional annotation analysis was performed using DAVID bioinformatics resources. Immunofluorescence and multiple reaction monitoring (MRM) MS methods were used to confirm prospective biomarkers in SLE mouse strains as well as human serum samples. Results Proteomic profiling of kidney tissues from SLE and control mice resulted in the identification of more than 3800 unique proteins. Pathway analysis revealed a number of dysregulated molecular pathways that may be mechanistically involved in renal pathology, including phagosome and proximal tubule bicarbonate reclamation pathways. Proteomic analysis supported by human transcriptomic data and pathway analysis revealed Coronin-1A, Ubiquitin-like protein ISG15, and Rho GDP-dissociation inhibitor 2, as potential LN biomarkers. These results were further validated in other SLE mouse strains using MRM-MS. Most importantly, experiments in humans showed that measurement of Coronin-1A in human sera using MRM-MS can segregate LN patients from SLE patients without nephritis with a high sensitivity (100%) and specificity (100%). Conclusions These preliminary findings suggest that serum Coronin-1A may serve as a promising non-invasive biomarker for LN and, upon validation in larger cohorts, may be employed in the future as a screening test for renal disease in SLE patients.

Temperate rainforest soils of the Pacific Northwest are often carbon (C) rich and encompass a wide range of fertility, reflecting varying nitrogen (N) and phosphorus (P) availability. Soil resource stoichiometry (C : N : P) may provide an effective measure of site nutrient status and help refine species-dependent patterns in forest productivity across edaphic gradients. We determined mineral soil and forest floor nutrient concentrations across very wet (perhumid) rainforest sites of southwestern Vancouver Island (Canada) and employed soil element ratios as covariates in a long-term planting density trial to test their utility in defining basal area growth response of four conifer species. There were strong positive correlations in mineral soil C, N, and organic P (Po) concentrations and close alignment in C : N and C : Po both among and between substrates. Stand basal area after 5 decades was best reflected by mineral soil and forest floor C : N, but in either case included a significant species–soil interaction. The conifers with ectomycorrhizal fungi had diverging growth responses displaying either competitive (Picea sitchensis) or stress-tolerant (Tsuga heterophylla, Pseudotsuga menziesii) attributes, in contrast to a more generalist response by an arbuscular mycorrhizal tree (Thuja plicata). Despite the consistent patterns in organic matter quality, we found no evidence for increased foliar P concentrations with declining element ratios (C : Po or C : Ptotal) as we did for N. The often high C : Po ratios (as much as 3000) of these soils may reflect a stronger immobilization sink for P than N, which, along with ongoing sorption of PO4-, could limit the utility of C : Po or N : Po to adequately reflect P supply. The dynamics and availability of soil P to trees, particularly as Po, deserves greater attention, as many perhumid rainforests were co-limited by N and P, or, in some stands, possibly P alone.

Background. Diverticulosis is not well characterized in the Caribbeans. Our aim was to compare the anatomical presentation of colonic diverticulosis in African Caribbeans (group AC) versus Europeans (group E) and severity. Methods. We conducted a prospective controlled study involving 274 patients admitted for lower gastrointestinal haemorrhage (LGIH) in France (center 1: Guadeloupe; center 2: La Roche-sur-Yon); 179 cases with diverticular haemorrhage, including 129 in group AC and 40 in group E. Exploration of the colon included a detailed assessment of diverticula using a dedicated endoscopic grid. Results. AC and E had similar characteristics in terms of age, gender, previous history of LGIH, body mass index, dietary habits, and medications, but AC had significantly poorer hemodynamic parameters at admission and required more blood transfusions (66.7% vs. 42.5%; p=0.01) during hospitalization. Out of the 169 patients included in the study, a complete exploration of the colon was achieved in 81% (N = 137) (AC, n = 106; E, n = 31), and revealed right-side diverticulosis in AC (in 90.6%, included into a pancolonic form in 73.6% vs. 35.5%; p=0.0002) and left-side diverticulosis in E (in 96.8%, isolated form in 58.1% vs. 9.4%, p=0.0002). These data were confirmed by a sensitivity analysis using an endoscopic grid in 92 patients, achieving a higher frequency and larger size of diverticula in AC. Conclusion. Our study has shown that diverticulosis was pancolonic in AC and more frequently associated with more severe haemorrhage than the left-sided diverticulosis of Europeans. This anatomical presentation may be driven by the genetic background more than the environment and diet.

Background: Although prior studies have demonstrated racial disparities regarding acute coronary syndrome (ACS) care within private or mixed healthcare systems, few researchers have explored such disparities within universal healthcare systems. We aimed to evaluate the quality and outcomes of in-hospital ACS management for White patients vs patients of colour, within a universal healthcare context. Methods: We performed a post hoc analysis of the Acute Myocardial Infarction - Knowledge Translation to Optimize Adherence to Evidence-Based Therapy study, a cluster-randomized trial evaluating a knowledge-translation intervention at 24 hospitals in Quebec, Canada (years: 2009 and 2012). The primary endpoint was coronary catheterization. The secondary endpoints included in-hospital mortality, percutaneous and surgical coronary revascularization, major bleeding, total stroke, and discharge prescription of evidence-based medical therapy. Results: Of 3444 included patients, 2738 were White, and 706 were people of colour. The mean age was 68.2 years (33.3% women) among White patients and 69.5 years (36.0% women) among patients of colour. Patients of colour were less likely to undergo in-hospital coronary catheterization than were White patients (74.5% vs 80.3%, P = 0.001). This difference was attenuated after adjusting for patient-level characteristics (odds ratio 0.89; 95% confidence interval 0.73-1.09), and it was eliminated after adjusting for hospital-level characteristics (odds ratio 1.04; 95% confidence interval 0.73-1.49). Conclusions: Racial disparity in coronary catheterization for ACS persists within a universal healthcare context. Patients’ comorbidities and hospital-level factors may be partially responsible for this inequality. Future research on cardiovascular healthcare in patients with diverse racial/ethnic backgrounds in universal healthcare systems is needed to remediate racial inequality in ACS management. RÉsumÉ: Contexte: Bien que des études antérieures aient démontré l’existence de disparités raciales dans la prise en charge du syndrome coronarien aigu (SCA) au sein de systèmes de santé privés ou mixtes, peu de chercheurs ont étudié ces disparités au sein de systèmes universels de soins de santé. Nous avons cherché à évaluer la qualité et les résultats de la prise en charge du SCA à l’hôpital pour les patients blancs par rapport aux patients de couleur, dans un contexte de soins de santé universels. Méthodologie: Nous avons effectué une analyse a posteriori de l’étude AMI-OPTIMA, un essai sur échantillon en grappes aléatoire évaluant une intervention d’application des connaissances dans 24 hôpitaux du Québec, au Canada (années : 2009 et 2012). Le paramètre d’évaluation principal était le cathétérisme coronaire. Les paramètres d’évaluation secondaires comprenaient la mortalité à l’hôpital, la revascularisation coronaire percutanée et chirurgicale, l’hémorragie majeure, l’accident vasculaire cérébral et la prescription au congé d’un traitement médical fondé sur des données probantes. Résultats: Sur les 3444 patients étudiés, 2738 étaient blancs et 706 étaient des personnes de couleur. L’âge moyen était de 68,2 ans (33,3 % de femmes) chez les patients blancs, et de 69,5 ans (36,0 % de femmes) chez les patients de couleur. Les patients de couleur étaient moins susceptibles de subir un cathétérisme coronaire à l’hôpital que les patients blancs (74,5 % contre 80,3 %, p = 0,001). Cette différence a été atténuée après ajustement pour tenir compte des caractéristiques des patients (rapport de cotes : 0,89; intervalle de confiance [IC] à 95 % : 0,73-1,09), et éliminée après ajustement pour tenir compte des caractéristiques des hôpitaux (rapport de cotes : 1,04; IC à 95 % : 0,73-1,49). Conclusions: La disparité raciale en ce qui a trait au cathétérisme coronaire pour un SCA persiste dans un contexte de soins de santé universels. Les comorbidités des patients et des facteurs liés à l’hôpital peuvent être partiellement responsables de cette inégalité. De plus amples recherches sur les soins cardiovasculaires chez les patients de diverses origines raciales ou ethniques dans les systèmes universels de soins de santé sont nécessaires pour remédier aux inégalités raciales dans la prise en charge du SCA.

Les effets d’un décès périnatal ont été largement documentés, mais on a rarement proposé un regard englobant sur le décès périnatal comme point de jonction temporelle à partir duquel bifurquent le parcours de vie des personnes touchées. L’approche processuelle permet de complexifier l’examen de la fausse couche en introduisant une conception « épaisse » de la temporalité, et d’examiner des phénomènes qui ont été jusqu’ici perçus indépendamment les uns des autres. Des entrevues semi-structurées ont été menées auprès de 48 femmes du Québec ayant vécu une fausse couche précoce. Une analyse thématique a permis de dégager quatre sphères touchées par cette bifurcation : 1. (para)professionnelle ; 2. conjugale ; 3. parentale ; 4. existentielle. L’analyse a permis ainsi de dégager les contours de la bifurcation générée par la fausse couche, en termes d’imprévisibilité, d’irréversibilité et de contagion, et de mettre en lumière les différents enchevêtrements qui sous-tendent cette bifurcation.

Abstract This paper examines the effects of a new form of the extended generalized uncertainty principle in the Snyder–de Sitter model on the thermodynamics of the Schwarzschild and Reissner–Nordström black holes. Firstly, we present a generalization of the minimal length uncertainty relation with two deformation parameters. Then we obtain the corrected mass–temperature relation, entropy and heat capacity for Schwarzschild black hole. Also we investigate the effect of the corrected uncertainty principle on the thermodynamics of the charged black holes. Our discussion of the corrected entropy involves a heuristic analysis of a particle which is absorbed by the black hole. Finally, we compare the thermodynamics of a charged black hole with the thermodynamics of a Schwarzschild black hole and with the usual forms, that is, without corrections to the uncertainty principle.

Abstract We examine the effects of gravitational fields produced by topological defects on a Dirac field and a Dirac oscillator in a spinning cosmic string spacetime. We obtain the eigenfunctions and the energy levels of the relativistic field in that background and consider the effect of various parameters, such as the frequency of the rotating frame, the oscillator’s frequency, the string density and other quantum numbers.

Abstract Background Negative experiences in early life can induce long-lasting effects on the welfare, health, and performance of farm animals. A delayed placement of chicks in rearing houses has negative effects on their performance, and results in fecal-specific odors detectable by rats. Based on this observation, the volatile organic compounds (VOCs) and metabolites from the feces of 12-day-old chickens were screened for early markers of response to negative events using gas-chromatography and liquid-chromatography coupled with mass spectrometry (GC-MS, LC-HRMS). Results The low reproducibility of solid-phase micro-extraction of the VOCs followed by GC-MS was not suitable for marker discovery, in contrast to liquid extraction of metabolites from freeze-dried feces followed by GC-MS or LC-HRMS analysis. Therefore, the fecal metabolome from 12-day-old chicks having experienced a normal or delayed placement were recorded by GC-MS and LC-HRMS in two genotypes from two experiments. From both experiments, 25 and 35 metabolites, respectively explaining 81% and 45% of the difference between delayed and control chickens, were identified by orthogonal partial least-squares discriminant analysis from LC-HRMS and GC-MS profiling. Conclusion The sets of molecules identified will be useful to better understand the chicks’ response to negative events over time and will contribute to define stress or welfare biomarkers.

Introduction and aim: Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. Material and methods: A prospective cohort of adult patients with CHC treated in French general hospitals. Results: Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. Conclusions: The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.

The growing demand for molecules of interest from microalgal biomass, such as phycobiliproteins, has led to an accumulation of unused by-products. For example, phycocyanin, obtained by the extraction of Spirulina, generated cakes rich in non-polar molecules of interest, such as free fatty acids (FFAs). These FFAs were generally considered as markers of lipidome degradation, but represented a relevant alternative to topical antibiotics, based on a biomimetic approach. In order to develop a sustainable Spirulina biorefinery scheme, different pretreatments and alternative solvents were screened to identify the best combination for the valorization of FFAs. Thus, five pre-treatments were studied including a phycocyanin extraction by-product. The following three biobased solvents were selected: ethyl acetate (EtOAc), dimethyl carbonate (DMC) and a fatty acid-based natural deep eutectic solvent (NaDES). The pigment and fatty acid profiles were established by spectroscopic and chromatographic approaches. NaDES demonstrated superior extraction capacity and selectivity compared to other biobased solvents, regardless of pretreatment. In contrast, EtOAc and DMC showed a greater diversity of FFAs, with a predominance of polyunsaturated fatty acids (PUFAs). The by-product has also been highlighted as a relevant raw material facilitating the recovery of FFAs. These results pave the way for a green biorefinery of the lipid fraction and phycobiliproteins of microalgae.

SERCA1a is an ATPase calcium pump that transports Ca2+ from the cytoplasm to the sarco/endoplasmic reticulum lumen. Sarcolipin (SLN), a transmembrane peptide, regulates the activity of SERCA1a by decreasing its Ca2+ transport rate, but its mechanism of action is still not well-understood. To decipher this mechanism, we have performed normal mode analysis in the all-atom model, with the SERCA1a-SLN complex, or the isolated SERCA1a, embedded in an explicit membrane. The comparison of the results allowed us to provide an explanation at the atomic level for the action of SLN that is in good agreement with experimental observations. In our analyses, the presence of SLN locally perturbs the TM6 transmembrane helix and as a consequence modifies the position of D800, one of the key metal-chelating residues. Additionally, it reduces the flexibility of the gating residues, V304, and E309 in TM4, at the entrance of the Ca2+ binding sites, which would decrease the affinity for Ca2+. Unexpectedly, SLN has also an effect on the ATP binding site more than 35 Å away, due to the straightening of TM5, a long helix considered as the spine of the protein. The straightening of TM5 modifies the structure of the P-N linker that sits above it, and which comprises the 351DKTG354 conserved motif, resulting in an increase of the distance between ATP and the phosphorylation site. As a consequence, the turn-over rate could be affected. All this gives SERCA1a the propensity to go toward a Ca2+ low-affinity E2-like state in the presence of SLN and toward a Ca2+ high-affinity E1-like state in the absence of SLN. In addition to a general mechanism of inhibition of SERCA1a regulatory peptides, this study also provides an insight into the conformational transition between the E2 and E1 states.

Optimal management of gilt reproduction requires oestrus synchronization. Hormonal treatments are used for this purpose, but there is a growing demand for non-hormonal alternatives, especially in organic farms. The boar effect is an important alternative opportunity to induce and synchronize oestrus without hormones. Before puberty, gilts exhibit a ‘waiting period’ during which boar exposure could induce and synchronize the first ovulation. We searched for salivary biomarkers of this period of boar effect receptivity to improve detection of the gilts to stimulate with the perspective of enhancing the efficacy of the boar effect. Saliva samples were collected from 30 Large-White×Landrace crossbred gilts between 140 and 175 days of age. Gilts were exposed twice a day to a boar and subjected to oestrus detection from 150 to 175 days of age. Among the 30 gilts, 10 were detected in oestrus 4 to 7 days after the first introduction of the boar and were considered receptive to the boar effect, 14 were detected in oestrus more than 8 days after first boar contact, and six did not show oestrus and were considered non-receptive. Saliva samples from six receptive and six non-receptive gilts were analyzed for steroidome and for metabolome using gas chromatography coupled to tandem mass spectrometry and 1H nuclear magnetic resonance spectroscopy, respectively. Four saliva samples per gilt were analyzed: 25 days and 11 days before boar introduction, the day of boar introduction, 3 days later for receptive gilts or 7 days later for non-receptive gilts. Twenty-nine steroids and 31 metabolites were detected in gilt saliva. Salivary concentrations of six steroids and three metabolites were significantly different between receptive and non-receptive gilts: progesterone and glycolate 25 days before boar introduction, 3α5β20α- and 3β5α20β-hexahydroprogesterone, dehydroepiandrosterone, androstenediol, succinate, and butyrate 11 days before boar introduction, and 3β5α-tetrahydroprogesterone on the day of boar introduction. Thus, nine potential salivary biomarkers of boar effect receptivity were identified in our experimental conditions. Further studies with higher numbers of gilts and salivary sampling points are necessary to ascertain their reliability.

The loss of an infant during the perinatal period has been recognized as a complex and potentially traumatic life event and can have a significant impact on women’s mental health. However, often times, psychological aftercare is typically not offered, and manualized interventions are rarely used in clinical care practice and have seldom been evaluated. In recent years, a growing number of studies have demonstrated the efficacy of virtual reality (VR) interventions to facilitate the expression and coping with emotions linked to a traumatic event. The objective of the proposed paper is to present the protocol of a randomized control trial aimed to assess a novel VR-based intervention for mothers who experienced a perinatal loss. We hypothesize that the VR-based intervention group will show significantly reduced symptoms related to grief, postnatal depression and general psychopathology after treatment relative to a treatment-as-usual (TAU) group. Participants would be randomly assigned to the TAU + VR or to the VR + TAU condition. The TAU condition as well as the VR-based intervention will last 3 weeks, after which women will complete a post-assessment. The proposed VR-based intervention will consist in three weekly sessions focused, respectively on: (1) collect information about the loss and psychoeducation about perinatal grief, and introduction to the virtual environment; (2) through the use of the virtual environment, women will be assisted in the elaboration and acceptation of loss; (3) recreate, using the specific features of the virtual environment a positive metaphor representing woman’s future life. VR has proved to be a valid intervention tool in clinical psychology, and in the last years VR technologies have become more affordable to be used in clinical practice. With the present study we propose to answer to the unquestionable need for interventions addressed to ameliorate the emotional effects in women who experienced perinatal loss, by exploiting also the therapeutic opportunities offered by a new technology as VR.

We present a strategy for searching for heavy neutrinos at the Large Hadron Collider using the MoEDAL Experiment's MAPP detector. We hypothesize the heavy neutrino to be a member of a fourth generation lepton doublet, with the electric dipole moment (EDM) introduced within a dimension-five operator. In this model the heavy neutrino is produced in association with a heavy lepton. According to our current experimental and theoretical understanding, the electric dipole moment of this heavy neutrino may be as high as 10−15 e cm. Taking advantage of the sensitivity of MoEDAL detector, we examine the possibility of detecting such a heavy neutrino in the MAPP as an apparently fractionally charged particle, via ionization due to the neutrino's EDM. Keywords: Heavy neutrino, Electric dipole moment, Heavy lepton, LHC, MilliQan, MoEDAL

Stemming from a critical reflexion on the concept of disenfranchised grief (DG), this article examines the way (non) acknowledgement unfolds in the context of perinatal death/grief, along spatial and temporal lines. It was shown that acknowledgment tends to decrease as we move along the temporal axis (i.e. the further away we move from the time of the perinatal death), and as we move along the spatial axis (i.e. more homogeneous in the medical sphere, less so in the family and social sphere, and often absent in the professional sphere). (Non) acknowledgment is neither monolithic, nor binary or static. Tangibility, social scripts and the relationship to the emotions of other are three notions that have been found to help us make sense of these results.

We have previously reported that the female genital tract (FGT) of Beninese HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs), presented elevated frequencies of a myeloid HLA-DR+CD14+CD11c+ population presenting “tolerogenic” monocyte derived dendritic cells (MoDC) features. In order to assess whether a differential profile of monocytes may be involved in the generation of these genital MoDCs, we have herein characterized the blood monocyte compartment of Beninese HESNs (HIV-uninfected ≥ 10 years CSWs) and relevant controls (HIV-uninfected 2.5–5 years CSWs herein termed “early HESNs”), HIV-infected CSWs, and low-risk HIV-uninfected women from the general population. Transcriptomic analyses by RNA-Seq of total sorted blood monocytes demonstrate that in comparison to the control groups, HESNs present increased expression levels of FCGR2C, FCAR, ITGAX, ITGAM, CR2, CD68, and CD163 genes, associated with effector functions. Moreover, we found increased expression levels of genes associated with protection/control against SHIV/HIV such as CCL3, CCL4, CCL5, BHLHE40, and TNFSF13, as well as with immune regulation such as IL-10, Ahr, CD83, and the orphan nuclear receptor (NR)4A1, NR4A2, and NR4A3. Through multicolor flow cytometry analyses, we noticed that the frequencies of intermediate and non-classical monocyte populations tended to be elevated in the blood of HESNs, and exhibited increased expression levels of effector CD16, CD11c, CD11b, as well as regulatory HLA-G, IL-10, and IFN-α markers when compared to HIV-uninfected women and/or HIV-infected CSWs. This profile is compatible with that previously reported in the FGT of HESNs, and likely confers an enormous advantage in their resistance to HIV infection.

We update our previous search for trapped magnetic monopoles in LHC Run 2 using nearly six times more integrated luminosity and including additional models for the interpretation of the data. The MoEDAL forward trapping detector, comprising 222 kg of aluminium samples, was exposed to 2.11 fb−1 of 13 TeV proton–proton collisions near the LHCb interaction point and analysed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to the Dirac charge or above are excluded in all samples. The results are interpreted in Drell–Yan production models for monopoles with spins 0, 1/2 and 1: in addition to standard point-like couplings, we also consider couplings with momentum-dependent form factors. The search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.

Abstract Background Prenatal education is a core component of perinatal care and services provided by health institutions. Whereas group prenatal education is the most common educational model, some health institutions have opted to implement online prenatal education to address accessibility issues as well as the evolving needs of future parents. Various studies have shown that prenatal education can be effective in acquisition of knowledge on labour and delivery, reducing psychological distress and maximising father’s involvement. However, these results may depend on educational material, organization, format and content. Furthermore, the effectiveness of online prenatal education compared to group prenatal education remains unclear in the literature. This project aims to evaluate the impacts of group prenatal education and online prenatal education on health determinants and users’ health status, as well as on networks of perinatal educational services maintained with community-based partners. Methods This multipronged mixed methods study uses a collaborative research approach to integrate and mobilize knowledge throughout the process. It consists of: 1) a prospective cohort study with quantitative data collection and qualitative interviews with future and new parents; and 2) a multiple case study integrating documentary sources and interviews with stakeholders involved in the implementation of perinatal information service networks and collaborations with community partners. Perinatal health indicators and determinants will be compared between prenatal education groups (group prenatal education and online prenatal education) and standard care without these prenatal education services (control group). Discussion This study will provide knowledge about the impact of online prenatal education as a new technological service delivery model compared to traditional group prenatal education. Indicators related to the complementarity of these interventions and those available in community settings will refine our understanding of regional perinatal services networks. Results will assist decision-making regarding service organization and delivery models of prenatal education services. Protocol version Version 1 (February 9 2018).