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Abstract Background Posttraumatic stress disorder (PTSD) is a common mental disorder. However, many cases of PTSD remain untreated because of limited healthcare resources and other treatment-seeking barriers. Effective internet-based interventions could help to improve access to PTSD treatments. Therefore, the main objective of the planned randomized controlled trial is to evaluate the efficacy of the Lithuanian version of the guided internet-based self-help programme (Spring) in reducing ICD-11 PTSD symptoms. Methods The planned sample size is 50 participants exposed to different traumatic experiences. Participants eligible for the study will be randomized into two study groups: the immediate treatment group and the delayed treatment control group. Both groups will receive guided trauma-focused ICBT intervention, but the delayed treatment group will receive access to the programme five months after randomization. The International Trauma Interview (ITI) will be used for the assessment of ICD-11 PTSD symptoms at pre-treatment, post-treatment, and at a 3-month follow-up. Changes in disturbances in self-organization, depression and anxiety levels, as well as posttraumatic cognitions and trauma-related shame, will also be evaluated. In addition, associations between changes in symptoms of PTSD and readiness for treatment, treatment expectations and working alliance will be explored. Changes in treatment outcomes will be evaluated using multiple Latent Change Models. Discussion This study is expected to contribute to valuable knowledge on the efficacy of internet-based interventions for posttraumatic stress disorder. Trial registration ClinicalTrials.gov NCT06475716. Registered on 25 June 2024.

Ischia island represents the westernmost portion of the Phlegraean Volcanic District (Campania Region, Italy) and is characterized by the presence of Mt. Epomeo, a giant centrally located resurgent volcanic horst. This horst is controlled by fault systems and magmatic dynamics able to generate recurrent seismicity. Such seismicity, associated with the presence of volcanic terrains with different degrees of erodibility, makes Ischia highly subjected to several ground instability phenomena such as landslides. This multidisciplinary study aimed to map the seismically induced landslide susceptibility of the island, taking into account the Md 4.0 earthquake that occurred on August 21, 2017, as a reference seismic event. Eight parameters were isolated as relevant predisposing factors for landslide occurrence and combined, through GIS elaborations, to compute a numerical index (SNAP index) that quantified the seismically induced landslide susceptibility for each 5 × 5 m area. The resulting map, through five classes of susceptibility, highlights that the highest exposed areas are mainly localized along the N–NW flanks of Mt. Epomeo, involving mainly the municipality of Casamicciola Terme. Moreover, the map is discussed considering the spatial distribution of historical and recent seismically induced ground effects, an ERT field survey carried out on significant test sites, and the displacement map obtained by 2015–2022 InSAR data.

Abstract Background The primary objective of this cross-sectional study, conducted in Québec and Bristish Columbia (Canada) between February 2021 and January 2022, was to measure the prevalence of viral RNA in oronasal and rectal swabs and serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) amongst cats living in households with at least one confirmed human case. Secondary objectives included a description of potential risk factors for the presence of SARS-CoV-2 antibodies and an estimation of the association between the presence of viral RNA in swabs as well as SARS-CoV-2 antibodies and clinical signs. Oronasal and rectal swabs and sera were collected from 55 cats from 40 households at most 15 days after a human case confirmation, and at up to two follow-up visits. A RT-qPCR assay and an ELISA were used to detect SARS-CoV-2 RNA in swabs and serum SARS-CoV-2 IgG antibodies, respectively. Prevalence and 95% Bayesian credibility intervals (BCI) were calculated, and associations were evaluated using prevalence ratio and 95% BCI obtained from Bayesian mixed log-binomial models. Results Nine (0.16; 95% BCI = 0.08–0.28) and 38 (0.69; 95% BCI = 0.56–0.80) cats had at least one positive RT-qPCR and at least one positive serological test result, respectively. No risk factor was associated with the prevalence of SARS-CoV-2 serum antibodies. The prevalence of clinical signs suggestive of COVID-19 in cats, mainly sneezing, was 2.12 (95% BCI = 1.03–3.98) times higher amongst cats with detectable viral RNA compared to those without. Conclusions We showed that cats develop antibodies to SARS-CoV-2 when exposed to recent human cases, but detection of viral RNA on swabs is rare, even when sampling occurs soon after confirmation of a human case. Moreover, cats with detectable levels of virus showed clinical signs more often than cats without signs, which can be useful for the management of such cases.

Abstract There are two known mechanisms by which natural killer (NK) cells recognize and kill diseased targets: (i) direct killing and (ii) antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated an indirect NK cell activation strategy for the enhancement of human NK cell killing function. We did this by leveraging the fact that toll-like receptor 9 (TLR9) agonism within pools of human peripheral blood mononuclear cells (PBMCs) results in a robust interferon signaling cascade that leads to NK cell activation. After TLR9 agonist stimulation, NK cells were enriched and incorporated into assays to assess their ability to kill tumor cell line targets. Notably, differential impacts of TLR9 agonism were observed—direct killing was enhanced while ADCC was not increased. To ensure that the observed differential effects were not attributable to differences between human donors, we recapitulated the observation using our Natural Killer—Simultaneous ADCC and Direct Killing Assay (NK-SADKA) that controls for human-to-human differences. Next, we observed a treatment-induced decrease in NK cell surface CD16—known to be shed by NK cells post-activation. Given the essential role of CD16 in ADCC, such shedding could account for the observed differential impact of TLR9 agonism on NK cell-mediated killing capacity.

Abstract Background Patients who have recurrent atrial fibrillation (AF) following redo catheter ablation may eventually be managed with a pace‐and‐ablate approach, involving pacemaker implant followed by atrioventricular nodal ablation (AVNA). We sought to determine which factors would predict subsequent AVNA in patients undergoing redo AF ablation. Methods We analyzed patients undergoing redo AF ablations between 2013 and 2019 at our institution. Follow‐up was censored on December 31, 2021. Patients with no available follow‐up data were excluded. Time‐to‐event analysis with Cox proportional hazard regression was used to compare those who underwent AVNA to those who did not. Results A total of 467 patients were included, of whom 39 (8.4%) underwent AVNA. After multivariable adjustment, female sex (aHR 4.68 [95% CI 2.30–9.50]; p

Research suggests new foreign language (FL) words are learned more easily if their phonology follows the phonotactic rules of the native language. Very little is known, however, about the impact of orthography on FL learning. This study investigated the cognitive mechanisms supporting the learning of words with familiar and unfamiliar orthographies. Participants took part in learning and meaning recall tasks, as well as a series of cognitive tasks (short-term and working memory tasks and tasks assessing their phonological and acoustic abilities). Orthographic and phonological familiarity judgments were collected using another sample of participants. Using a mixed-effects model, the results showed that orthographic familiarity impacted FL word learning even after controlling for phonological familiarity. However, there were no interactions with cognitive abilities.

Objective Chronic pain affects approximately 7.6 million Canadians and access to care remains an issue. The Power Over Pain (POP) Portal offers immediate access to evidence-based resources ranging from low- (e.g. education, self-management), to high- (e.g. individual counseling) intensity. We explored the POP Portal's acceptability, usability, and perceived usefulness among patients newly referred to a tertiary care pain clinic. Methods We used a descriptive, qualitative approach with a prospective cohort of 60 adult patients recently referred to The Ottawa Hospital Pain Clinic. Patients were offered an orientation session and asked to participate in a seven-week follow-up interview. Data were thematically analyzed in an iterative process, whereby responses were reviewed and coded by two members of the research team. Results Of the 60 patients referred to the POP Portal by clinic clerks, 45 participated in the orientation session, and 40 completed a four-week follow-up. All 40 patients had used the POP Portal and recommended that we continue to offer the POP Portal to patients awaiting care. We identified overarching themes of acceptability (five subthemes), usability (ten subthemes), accessibility (three subthemes), and patient value of the POP Portal (three subthemes). This includes (1) the POP Portal provides easy access to chronic pain resources; (2) the POP Portal is helpful in developing an understanding of chronic pain; and (3) improvements to the POP Portal are needed to increase usability and foster a user-friendly experience. Conclusions The POP Portal offers accessible and diverse resources for people living with pain awaiting a tertiary care consultation; however, patients would like to see resources specific to diagnosis. Improvements are suggested to allow greater increase the POP Portal usability.

The complexity of cancer requires a comprehensive approach to understand its diverse manifestations and underlying mechanisms. Initially outlined by Hanahan and Weinberg in 2000 and updated in 2010, the hallmarks of cancer provide a conceptual basis for understanding inherent variability in cancer biology. Recent expansions have further elucidated additional hallmarks, including phenotypic plasticity and senescent cells. The International Agency for Research on Cancer (IARC) has identified the key characteristics of carcinogens (KCCs) to evaluate their carcinogenic potential. We analyzed chemicals of concern for environmental exposure that interact with specific receptors to induce genomic instability, epigenetic alterations, immune suppression, and receptor-mediated effects, thereby contributing to chronic inflammation. Despite their varying degrees of carcinogenicity, these chemicals have similar KCC profiles. Our analysis highlights the pivotal role of receptor binding in activating most other KCCs, underscoring their significance in cancer initiation. Although KCCs are associated with early molecular or cellular events, they do not encompass processes directly linked to full cellular malignancy. Thus, there is a need to integrate clear endpoints that anchor KCCs to the acquisition of a complete malignant phenotype into chemical testing. From the perspective of toxicology and cancer research, an all-encompassing strategy that incorporates both existing and novel KCCs and cancer hallmarks is essential to enable the targeted identification of prevalent carcinogens and facilitate zone-specific prevention strategies. To achieve this goal, collaboration between the KCC and cancer hallmarks communities becomes essential.

Madalina Patron,1,2,* Mattias Neset,1,2,* Mariia Mielkozorova,2,* Daniel G Bisson,1,3,* Marie Vigouroux,4 Juan Pablo Cata,5,6 Pablo M Ingelmo,4,7,8 Jean A Ouellet,1,3 Lisbet Haglund,1,3,* Svetlana V Komarova1,2,* 1Shriners Hospital for Children, Montreal, Canada; 2Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, Canada; 3Orthopaedic Research Laboratory, Department of Surgery, McGill University, Montreal, Canada; 4Edwards Family Interdisciplinary Center for Complex Pain, Montreal Children’s Hospital, Montreal, QC, Canada; 5Department of Anesthesia and Perioperative Medicine, The University of Texas – MD Anderson Cancer Center, Houston, TX, USA; 6Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA; 7Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada; 8Research Institute, McGill University Health Center, Montreal, Canada*These authors contributed equally to this workCorrespondence: Svetlana V Komarova, Shriners Hospital for Children, 1003 Decarie Boulevard, Montreal, Quebec, H4A 0A9, Canada, Tel +1 514 282-7153, Email svetlana.komarova@mcgill.caPurpose: Pain is an understudied physiological effect of spaceflight. Changes in inflammatory and tissue degradation markers are often associated with painful conditions. Our aim was to evaluate the changes in markers associated with tissue deterioration after a short-term spaceflight.Patients and Methods: Plasma levels of markers for systemic inflammation and tissue degeneration markers were assessed in two astronauts before and within 24 h after the 17-day Axiom Space AX-1 mission.Results: After the spaceflight, C-reactive protein (CRP) was reduced in both astronauts, while INFγ, GM-CSF, TNFα, BDNF, and all measured interleukins were consistently increased. Chemokines demonstrated variable changes, with consistent positive changes in CCL3, 4, 8, 22 and CXCL8, 9, 10, and consistent negative change in CCL8. Markers associated with tissue degradation and bone turnover demonstrated consistent increases in MMP1, MMP13, NTX and OPG, and consistent decreases in MMP3 and MMP9.Conclusion: Spaceflight induced changes in the markers of systemic inflammation, tissue deterioration, and bone resorption in two astronauts after a short, 17-day, which were often consistent with those observed in painful conditions on Earth. However, some differences, such as a consistent decrease in CRP, were noted. All records for the effect of space travel on human health are critical for improving our understanding of the effect of this unique environment on humans.Keywords: spaceflight, astronaut, cytokine, interleukin, chemokine, bone turnover

Abstract Background Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. Methods From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. Results 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49–2.09] and 1.57 [1.35–1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13–1.67] and 1.47 [1.24–1.75], respectively). Conclusions Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Lahars represent some of the most dangerous phenomena in volcanic areas for their destructive power, causing dramatic changes in the landscape with no premonitory signs and impacting the population and infrastructure. In this regard, the Campanian Plain turns out to be very prone to the development of these phenomena, since the slopes of the Somma–Vesuvius and Campi Flegrei volcanoes, along with the Apennine reliefs, are mantled by pyroclastic deposits that can be easily remobilized, especially after intense and/or prolonged rainfall. This study focuses on the analysis of pyroclastic fall and flow deposits and of the syn- and post-eruptive lahar deposits related to two sub-Plinian eruptions of Vesuvius in 472 CE (Pollena) and 1631. To begin with, historical and field data from the existing literature and from hundreds of outcrops were collected and organized into a database, which was integrated with several new pieces of data. In particular, stratigraphic, sedimentological (facies analysis and laboratory), and archeological analyses were carried out, in addition to rock magnetic investigations and impact parameter calculations. The new data are also referenced to the finding of ash beds in more distal areas, which were included in new isopach maps for the two sub-Plinian eruptions. The results show that for both eruptions the distribution of the primary deposits is wider than previously known. A consequence of these results is that a wider areal impact should be expected in terms of civil protection, as the sub-Plinian scenario is the reference one for a future large eruption of Vesuvius. Such a distribution of the pyroclastic deposits directly affects the one of the lahar deposits, also because a significant remobilization took place during and after the studied eruptions, which involved distal phreatomagmatic ash. From these integrated analyses, it was possible to constrain the timing of the deposition and the kind of deposits remobilized (pyroclastic fall vs. flow), and it was possible to calculate the velocities and dynamic pressures of the lahars and ultimately infer the lahar transport and emplacement mechanisms. The multidisciplinary approach adopted in this work shows how it is crucial to assess the impact of lahars in densely populated areas even at distances of several to tens of kilometers from active volcanoes. This especially applies to large parts of the densely populated areas around Somma–Vesuvius up to the nearby Apennine valleys.

In this study we present a novel general methodology for probabilistic volcanic hazard assessment (PVHA) for lahars. We apply the methodology to perform a probabilistic assessment in the Campanian Plain (southern Italy), focusing on syn-eruptive lahars from a reference size eruption from Somma–Vesuvius. We take advantage of new field data relative to volcaniclastic flow deposits in the target region (Di Vito et al., 2024b) and recent improvements in modelling lahars (de' Michieli Vitturi et al., 2024). The former allowed defining proper probability density functions for the parameters related to the flow initial conditions, and the latter allowed computationally faster model runs. In this way, we are able to explore the effects of uncertainty in the initial flow conditions on the invasion of lahars in the target area by sampling coherent sets of values for the input model parameters and performing a large number of simulations. We also account for the uncertainty in the position of lahar generation by running the analysis on 11 different catchments threatening the Campanian Plain. The post-processing of the simulation outputs led to the production of hazard curves for the maximum flow thickness reached on a grid of points covering the Campanian Plain. By cutting the hazard curves at selected threshold values, we produce a portfolio of hazard maps and probability maps for the maximum flow thickness. We also produce hazard surface and probability maps for the simultaneous exceeding of pairs of thresholds in flow thickness and dynamic pressure. The latter hazard products represent, on one hand, a novel product in PVHA for lahars and, on the other hand, a useful means of impact assessment by assigning a probability to the occurrence of lahars that simultaneously have a relevant flow thickness and large dynamic pressure.

Abstract Aims Heart failure (HF) is a chronic disease affecting 64 million people worldwide and places a severe burden on society because of its mortality, numerous re‐hospitalizations and associated costs. HeartLogic™ is an algorithm programmed into implanted devices incorporating several biometric parameters which aims to predict HF episodes. It provides an index which can be monitored remotely, allowing pre‐emptive treatment of congestion to prevent acute decompensation. We aim to assess the impact and security of pre‐emptive HF management, guided by the HeartLogic™ index. Methods and results The HeartLogic™ France Cohort Study is an investigator‐initiated, prospective, multi‐centre, non‐randomized study. Three hundred ten patients with a history of HF (left ventricular ejection fraction ≤40%; or at least one episode of clinical HF with elevated NT‐proBNP ≥450 ng/L) and implanted with a cardioverter defibrillator enabling HeartLogic™ index calculation will be included across 10 French centres. The HeartLogic™ index will be monitored remotely for 12 months and in the event of a HeartLogic™ index ≥16, the local investigator will contact the patient for assessment and adjust HF treatment as necessary. The primary endpoint is unscheduled hospitalization for HF. Secondary endpoints are all‐cause mortality, cardiovascular death, HF‐related death, unscheduled hospitalizations for ventricular or atrial arrhythmia and HeartLogic™ index evolution over time. Blood samples will be collected for biobanking, and quality of life will be assessed. Finally, the safety of a HeartLogic™‐triggered strategy for initiating or increasing diuretic therapy will be assessed. A blind and independent committee will adjudicate the events. Conclusions The HeartLogic™ France Cohort Study will provide robust real‐world data in a cohort of HF patients managed with the HeartLogic™ algorithm allowing pre‐emptive treatment of heart failure exacerbations.