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Abstract Environmental cleaning is essential to patient and health worker safety, yet it is a substantially neglected area in terms of knowledge, practice, and capacity-building, especially in resource-limited settings. Public health advocacy, research and investment are urgently needed to develop and implement cost-effective interventions to improve environmental cleanliness and, thus, overall healthcare quality and safety. We outline here the CLEAN Group Consensus exercise yielding twelve urgent research questions, grouped into four thematic areas: standards, system strengthening, behaviour change, and innovation.

Abstract Background In contrast with Advanced Footwear Technology-AFT running shoes for long-distance, little is known about AFT sprint spikes on performance and acceleration parameters. However, their use has become widespread since the Tokyo 2020 Olympics, and knowledge of their effects would seem to be an essential starting point before any clinical or socio-economic considerations. Objectives Our objectives were to determine intra- and inter-subject sprinting performance modifications with Nike® AFT spikes (NAS) compared to standard spiked-shoes (SS). Methods Healthy regional to national sprint athletes (n = 21, ≥ 750 pts World Athletics) performed 16 repetitions of 30-m sprints with either the NAS or SS condition during a single session, based on the multiple N-of-1 method, with pairwise randomisation and double-blind procedure. Time on 30-m sprints (Stalker radar), force-velocity profile (F 0, V 0, V max, P max, RF, D RF and FVP slope), and confounding factors (wind and shoe mass) were measured. Statistical analyses included a mixed linear regression model for group analyses, and randomisation test inversion and non-overlap-of-all-pair (NAP) methods for intra-individual analysis. Results NAS improved 30-m time by a mean of − 0.02 s (SMD = 0.4, p = 0.014), with no interaction with any confounding factors. Significant changes were seen in velocity (V max : SMD = 0.9, p

Abstract Less than 15–20% of patients who meet the criteria for hereditary breast and ovarian cancer (HBOC) carry pathogenic coding genetic mutations, implying that other molecular mechanisms may contribute to the increased risk of this condition. DNA methylation in peripheral blood has been suggested as a potential epigenetic marker for the risk of breast cancer (BC). We aimed to discover methylation marks in peripheral blood associated with BC in 231 pre-treatment BC patients meeting HBOC criteria, testing negative for coding pathogenic variants, and 156 healthy controls, through methylation analysis by targeted bisulfite sequencing on 18 tumor suppressor gene promoters (330 CpG sites). We found i) hypermethylation in EPCAM (17 CpG sites; p = 0.017) and RAD51C (27 CpG sites; p = 0.048); ii) hypermethylation in 36 CpG-specific sites (FDR q

Connectivity, a fundamental concept in ecology, refers to the extent to which different habitats or ecosystems are interconnected through the movement of organisms, nutrients, and energy. Lateral hydrological connectivity (LHC) plays an especially critical role in shaping aquatic community organization in river-floodplain systems. However, a comprehensive understanding of various trait responses to LHC remains elusive. We characterized how attributes of fish community traits, specifically composition, divergence, and temporal variability respond to LHC in the Austrian-Hungarian floodplains of the Danube River using environmental DNA (eDNA) metabarcoding. Trait composition was quantified by community-level weighted means (CWM) as the degree of changes in trait responses along the LHC gradient from isolated oxbows to the main river. Divergence was measured using Rao’s quadratic functional diversity index and a null model approach to calculate standardized effect sizes (SES), with larger SES values indicating greater divergence and smaller values indicating convergence. Temporal variability, representing the degree of instability in community traits over time, was calculated using a functional beta diversity measure for multiple communities. Our findings revealed apparent compositional changes for many trait variables, highlighting the significance of LHC in shaping community functional diversity. Divergence patterns indicated that isolated habitats foster trait convergence presumably due to habitat filtering, whereas more connected areas promote trait divergence due to higher species richness and habitat availability. Temporal variability of traits associated with flow preference exhibited a hump-shaped relationship with LHC, suggesting intermediate connectivity zones are hotspots of ecological dynamism. The study suggests that examining composition, divergence, and temporal variability together provides a more complete understanding of trait responses to connectivity, stressing the importance of maintaining diverse connectivity levels in river-floodplain systems for effective conservation and ecosystem management.

Abstract Background Following publication of the 2009 World Health Organizations Guidelines for Hand Hygiene in Health Care, a debate has emerged regarding the relative antimicrobial efficacy of the different formats (rinse, gel, foam) of ABHRs and their ability to contribute to reduction of healthcare-associated infections (HAIs). Methods Data regarding the in-vivo antimicrobial efficacy of ABHRs and other factors that likely affect their effectiveness in reducing HAIs were reviewed, and a comprehensive review of studies that reported the effectiveness of each of the three ABHR formats to improve hand hygiene compliance and reduce HAIs was conducted. Results The amount of rubbing time it takes for hands to feel dry (dry time) is the major driver of ABHR antimicrobial efficacy. ABHR format is not a major factor, and several studies found that rinse, gel, and foam ABHRs have comparable in-vivo antimicrobial efficacy. Other factors that likely impact the ability of ABHRs to reduce transmission of healthcare-associated pathogens and HAIs include ABHR formulation, the volume applied to hands, aesthetic characteristics, skin tolerance, acceptance by healthcare personnel, and hand hygiene compliance rates. When accompanied by complementary strategies, promoting the use of each of the three ABHR formats has been associated with improvements in hand hygiene compliance rates. A review of 67 studies failed to identify an ABHR format that was significantly more effective in yielding statistically significant reductions in transmission of healthcare-associated pathogens or HAIs. Conclusions Current evidence is insufficient to definitively determine if one ABHR format is more effective in reducing transmission of healthcare-associated pathogens and HAIs. More rigorous studies such as multicenter randomized controlled trials comparing the different formats are needed to establish if one format is significantly more effective in reducing HAIs.

The aim of this study is to evaluate the efficacy of taking a daily supplement based on active compounds (AUDISTIM® Day Night: A D/N) in alleviating tinnitus-related disability, as suggested by previous real-life studies. This double-blind randomized placebo-controlled study was conducted in adults with mild to severe tinnitus receiving a 3-month supplementation with A D/N (magnesium, vitamins, phytochemicals) or placebo (excipients without active ingredients). Tinnitus-related handicap (THI), psychological stress (MSP-9), and sleep quality (PSQI) were assessed at baseline and during intervention, perceived impression of tinnitus improvement at the end of the follow-up. The full set analysis included 114 patients (59 A D/N, 55 placebo) aged 53.8 ± 11.4 years, 58% women, with fluctuating (45%) or permanent (55%) tinnitus from 9.3 ± 9.4 years. A D/N supplementation led to greater changes in THI (−13.2 ± 16.0 vs. −6.2 ± 14.4, p = 0.0158, Cohen’s d = 0.44) at 3 months (primary outcome), especially with continuous tinnitus (−15.0 ± 16.3 vs. −4.6 ± 12.8, p = 0.0065), and, to a lesser extent, at 1 month (−9.8 ± 13.1 for A vs. −4.3 ± 12.1, p = 0.0213). PSQI significantly improved over time in both groups, but MSP-9 only with A D/N. In lines with previous observational studies, both clinical (THI score > 7 pts) and statistical (vs. placebo) improvement, more pronounced in permanent tinnitus, demonstrate the effectiveness of the combination of active compounds and support its use in the management of mild to severe tinnitus.

Abstract Background Hand hygiene is a crucial measure for the prevention of healthcare-associated infections (HAIs). The Hand Hygiene Excellence Award (HHEA) is an international programme acknowledging healthcare facilities for their leadership in implementing hand hygiene improvement programmes, including the World Health Organisation’s Multimodal Improvement Strategy. This study aimed at summarising the results of the HHEA campaign between 2010 and 2021 and investigating the relationship between different hand hygiene parameters based on data from participating healthcare facilities. Methods A retrospective analysis was performed on datasets from HHEA forms, including data on hand hygiene compliance, alcohol-based handrub (ABHR) consumption, and Hand Hygiene Self-Assessment Framework (HHSAF) scores. Descriptive statistics were reported for each variable. The correlation between variables was inspected through Kendall’s test, while possible non-linear relationships between hand hygiene compliance, ABHR consumption and HHSAF scores were sought through the Locally Estimated Scatterplot Smoothing or logistic regression models. A tree-structured partitioning model was developed to further confirm the obtained findings. Results Ninety-seven healthcare facilities from 28 countries in three world regions (Asia-Pacific, Europe, Latin America) were awarded the HHEA and thus included in the analysis. HHSAF scores indicated an advanced hand hygiene promotion level (median 445 points, IQR 395–480). System change (100 [95–100] points) and institutional safety climate (85 [70–95] points) showed the highest and lowest score, respectively. In most cases, hand hygiene compliance was above 70%, with heterogeneity between countries. ABHR consumption above 20 millilitres per patient-day (ml/PD) was widely reported, with overall increasing trends. HHSAF scores were positively correlated with hand hygiene compliance (τ = 0.211, p = 0.007). We observed a positive correlation between compliance rates and ABHR consumption (τ = 0.193, p

Introduction: PRP is gaining increasing interest for pain relief and improvement of joint function in patients with knee osteoarthritis (KOA) but practices and results remain heterogeneous limiting its adoption as standard of care. Current international recommendations are to collect real-life evidence of efficacy with a systematic monitoring of PRP quality and patients' outcomes. We aimed to analyze the response of patients presenting KOA and treated with standardized PRP injection in routine care. We also investigated the potential contributing factors including patient's phenotype and PRP characteristics. Methods: Patients with symptomatic KOA and that failed first-line therapy received a single injection of a qualified PRP prepared using medical devices allowing to recover a high/very high volume of very pure PRP. Visual analogue scale (VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded at baseline and during 18 months follow-up. Results: 431 patients had available follow-up data at 3 months, 291 at 6 months, 137 at 12 months and 44 at 18 months. PRP induced a significant decrease of WOMAC score at all follow up endpoints (29.2 ± 19.2 at 3 months, p

This study compares cryogenic freezing (–80 °C and 0.5 m/s air velocity) and mechanical freezing (–40 °C and 4 m/s air velocity) conditions/methods on the quality of melon and apple tissues during a 90-day storage. Samples were analysed on the 7th, 30th, 60th, and 90th day for various qualities: pH, TSS, titratable acidity, total quality index, enzymology, vitamin C, firmness, colour, exudate, soluble protein, and microstructure. Results show pH, °Brix, titratable acidity, and total quality index changes after freezing. Trends differed between melon and apple. Melon pH increased after freezing, while apple pH decreased. Titratable acidity decreased post-freezing for both. °Brix in melon initially decreased but increased in apples with longer storage. Freezing conditions and storage durations affected total quality index. Melon firmness increased, while apple firmness decreased compared to fresh samples post-freezing. Freezing condition did not affect firmness, but storage duration impacted it. Colour was influenced by both freezing treatment and methods, as well as the duration of frozen storage for melons. The L* value decreased for both matrices following freezing treatment. The a* and b* values of apples increased after post-freezing treatment compared to fresh. The a* value of fresh and cryogenically frozen melons was similar. Colour differences were more pronounced for mechanically frozen samples, increasing during storage for apples, while a fluctuating trend was observed for melons. Apple samples exhibited a reduction in polyphenol oxidase (PPO) activity post-freezing, while peroxidase activity (POD) displayed some increase in melons. PPO activity was lower for cryogenic freezing, decreasing with storage, while POD activity was storage-duration impacted. Exudation was lower in cryogenic freezing for both matrices. Soluble protein content was higher in cryogenic frozen samples, though fluctuating. Cryogenic freezing slightly reduced pore sizes in apples, preserving microstructure better, unlike mechanical freezing which damaged cellular structure.

Abstract Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) pose threats to global health. Effective hand hygiene is essential for preventing HAIs and the spread of AMR in healthcare. We aimed to highlight the recent progress and future directions in hand hygiene and alcohol-based handrub (ABHR) use in the healthcare setting. In September 2023, 42 experts in infection prevention and control (IPC) convened at the 3rd International Conference on Prevention and Infection Control (ICPIC) ABHR Taskforce in Geneva, Switzerland. The purpose of this meeting was to provide a synthesis of recent evidence and formulate a research agenda on four critical areas for the implementation of effective hand hygiene practices: (1) ABHR formulations and hand rubbing techniques, (2) low-resource settings and local production of ABHR, (3) hand hygiene monitoring and technological innovations, and (4) hand hygiene standards and guidelines.

Abstract The 5th edition of the Global Ministerial Summit on Patient Safety was held in Montreux, Switzerland, in February 2023, delayed by three years due to the COVID-19 pandemic. The overarching theme of the summit was “Less Harm, Better Care – from Resolution to Implementation”, focusing on the challenges of implementation of infection prevention and control (IPC) strategies as well as antimicrobial stewardship programs (ASP) around the world. IPC strategies and ASP are of increasing importance due to the substantial burden of healthcare-associated infections and antimicrobial resistance threatening patient safety. Here, we summarize countries’ and regional experiences and activities related to the implementation of IPC strategies and ASP shared at the meeting. Full implementation of effective programs remains a major challenge in all settings due to limited support by political and healthcare leaders, and human and financial constraints. In addition, the COVID-19 pandemic challenged already well-established programs. By enforcing sustained implementation by dedicated, cross-disciplinary healthcare personnel with a broad skill set, a reduction in healthcare-associated infections and multidrug-resistant pathogens can be achieved, leading ultimately to improved patient safety.

The aim of this study is to examine the effect of the partial replacement of sand by Glass Fiber-Reinforced Polymer (GFRP) waste on the mechanical properties of cement mortars. Compressive and flexural tests were carried out on mortars containing 0, 3, 5, 10, and 15% (by volume) of GFRP waste. It appears that the incorporation of 3% GFRP waste did not significantly affect the mechanical strength. However, further increasing the GFRP waste content led to a reduction in the mechanical strength. The flexural strength seemed less affected than the compressive strength, since the decrease in flexural strength at a 10% replacement was only 37%, while it was 54% for the compressive strength. However, an improvement in the toughness of the mortar with an increase in the substitution rate was observed. The reference sample displayed a flexural toughness of 0.351 N·m, while the mortar incorporating 15% of GFRP exhibited a flexural toughness of 0.642 N·m. The reuse of GFRP waste in cementitious materials, therefore, constitutes an interesting recycling solution.

Abstract Bismuth ferrite has garnered considerable attention as a promising candidate for magnetoelectric spin-orbit coupled logic-in-memory. As model systems, epitaxial BiFeO3 thin films have typically been deposited at relatively high temperatures (650–800 °C), higher than allowed for direct integration with silicon-CMOS platforms. Here, we circumvent this problem by growing lanthanum-substituted BiFeO3 at 450 °C (which is reasonably compatible with silicon-CMOS integration) on epitaxial BaPb0.75Bi0.25O3 electrodes. Notwithstanding the large lattice mismatch between the La-BiFeO3, BaPb0.75Bi0.25O3, and SrTiO3 (001) substrates, all the layers in the heterostructures are well ordered with a [001] texture. Polarization mapping using atomic resolution STEM imaging and vector mapping established the short-range polarization ordering in the low temperature grown La-BiFeO3. Current-voltage, pulsed-switching, fatigue, and retention measurements follow the characteristic behavior of high-temperature grown La-BiFeO3, where SrRuO3 typically serves as the metallic electrode. These results provide a possible route for realizing epitaxial multiferroics on complex-oxide buffer layers at low temperatures and opens the door for potential silicon-CMOS integration.

Background: The quantification of electromyographic activity using surface electrodes is invaluable for understanding gait disorders in patients with central nervous system lesions. We propose to evaluate a commercially available low-cost system compared to a reference system in participants with stroke-related movement disorders in functional situations. Methods: Three hemiparetic participants performed three functional tasks: two treadmill walks at different speeds and a sit-to-stand test. The vastus lateralis and gastrocnemius medialis muscles were equipped with two EMG sensors. The comparison between the two EMG systems was based on 883 identified cycles. Spearman’s correlation coefficients (SCs), linear correlation coefficients (LCCs), and cross-correlation coefficients (CCCs) were calculated. Results: The main results indicate good to very good similarity of the EMG signals collected from the two tested sEMG systems. In the comfortable-walking condition, an SC of 0.894 ± 0.091 and an LCC of 0.909 ± 0.094 were noted. In the fast-walking condition, an SC of 0.918 ± 0.064 and an LCC of 0.935 ± 0.056 were observed. For the 1 min sit-to-stand test, an SC of 0.880 ± 0.058 and an LCC of 0.881 ± 0.065 were noted. Conclusions: This study demonstrates good to very good similarity between the two sEMG systems, enabling the analysis of muscle activity during functional tasks.

Background: Three-dimensional motion analysis using optoelectronic cameras and force platforms is typically used to quantify gait disorders. However, these systems have various limitations, particularly when assessing patients in an ecological environment. To address these limitations, several wearable devices have been developed. However, few studies have reported metrological information regarding their repeatability and sensitivity to change. Methods: A healthy adult performed 6 min walking tests with FeetMe® system insoles under different walking conditions overground and on a treadmill. The standard error of measurement (SEM), the minimum detectable differences (MDDs), and the effect size (ES) were calculated for spatio-temporal parameters, and the ground reaction force was calculated from the 16,000 steps recorded. Results: SEM values were below 3.9% for the ground reaction force and below 6.8% for spatio-temporal parameters. ES values were predominantly high, with 72.9% of cases between overground and treadmill conditions with induced asymmetry, and 64.5% of cases between treadmill conditions with and without induced asymmetry exhibiting an ES greater than 1.2. The minimum detectable differences ranged from 4.5% to 10.7% for ground reaction forces and 2.1% to 18.9% for spatio-temporal parameters. Conclusion: Our study demonstrated that the FeetMe® system is a reliable solution. The sensitivity to change showed that these instrumented insoles can effectively reflect patient asymmetry and progress.

Abstract A large stretch of the east coast of Australia experienced unprecedented rainfall and flooding over a two‐week period in early 2022. It is difficult to reliably estimate the likelihood of such a rare event from the relatively short observational record, so an alternative is to use data from an ensemble prediction system (e.g., a seasonal or decadal forecast system) to obtain a much larger sample of simulated weather events. This so‐called ‘UNSEEN’ method has been successfully applied in several scientific studies, but those studies typically rely on a single prediction system. In this study, we use data from the Decadal Climate Prediction Project to explore the model uncertainty associated with the UNSEEN method by assessing 10 different hindcast ensembles. Using the 15‐day rainfall total averaged over the river catchments impacted by the 2022 east coast event, we find that the models produce a wide range of likelihood estimates. Even after excluding a number of models that fail basic fidelity tests, estimates of the event return period ranged from 320 to 1814 years. The vast majority of models suggested the event is rarer than a standard extreme value assessment of the observational record (297 years). Such large model uncertainty suggests that multi‐model analysis should become part of the standard UNSEEN procedure.

BackgroundAdapted physical activity programs have shown promising results in reducing the physical, social and psychological side effects associated with breast cancer, but the extent to which they can be effectively adopted, implemented and maintained is unclear. The aim of this study is to use the framework to guide the planning and evaluation of programs according to the 5 following keys: Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate a fencing program under the French acronym RIPOSTE (Reconstruction, Image de soi, Posture, Oncologie, Santé, Thérapie, Escrime) literally in English (Reconstruction, Self-Image, Posture, Oncology, Health, Therapy, Fencing). This program is an innovative intervention focused on improving the quality of life (QoL) of breast cancer surgery patients through fencing.MethodsA convergent mixed methods pilot study was conducted to preliminary evaluate the different RE-AIM dimension of the pilot program. Twenty-four participants who have just undergone surgery for invasive breast cancer were randomly allocated in two groups: one group started immediately after their inclusion (Early RIPOSTE group) and the other started 3 months following their inclusion (Delayed RIPOSTE group). Participants answered a questionnaire at inclusion and at the end of the program on QoL, shoulder functional capacity, fatigue, anxiety-depression and physical activity.ResultsRIPOSTE program was able to reach mainly young and dynamic participants, attracted by the originality of fencing and keen to improve their physical condition. Regarding effectiveness, our results suggest a trend to the improvement of QoL, shoulder functional capacity, fatigue and anxiety-depression state, even without any significant differences between the Early RIPOSTE group and the Delayed RIPOSTE group.DiscussionsThe cooperation, exchanges and cohesion within the group greatly facilitated the adoption of the program, whereas interruptions during school vacations were the main barriers. The intervention was moderately well implemented and adherence to the protocol was suitable.ConclusionRIPOSTE is an acceptable and effective program for involving breast cancer survivors in physical activity, that needs to be tested at a larger scale to investigate its effectiveness, but has the potential to be transferred and scaled up worldwide.

Abstract Background Mosquitoes (Diptera: Culicidae) can have a significant negative impact on human health. The urbanization of natural environments and their conversion for agricultural use, as well as human population growth, may affect mosquito populations and increase the risk of emerging or re-emerging mosquito-borne diseases. We report on the variety and number of adult mosquitoes found in four environments with varying degrees of human impact (rural, urban, rice fields, and forest) located in a savannah zone of West Africa. Methods Mosquitoes were collected from two regions (Hauts-Bassins and Sud-Ouest) of Burkina Faso during five periods between August 2019 and June 2021. Sampling sites were grouped according to environment. Mosquitoes were collected using BG-Sentinel traps and double net traps, and Prokopack Aspirators. Statistical analyses were performed using R software version 4.1.2. Logistic regression, using generalised mixed linear models, was used to test the effect of environment on mosquito abundance and diversity. Alpha diversity analysis was also performed, using the vegan package. Results A total of 10,625 adult mosquitoes were collected, belonging to 33 species and five genera: Culex, Aedes, Anopheles, Mansonia, and Ficalbia. The most dominant species were Culex quinquefasciatus, Anopheles gambiae sensu lato and Aedes aegypti. Alpha diversity was similar in the two regions. Habitat had a significant effect on mosquito species richness, the Shannon index and the Simpson index. The rural environment had the highest species richness (n = 28) followed by the forest environment (n = 24). The highest number of mosquitoes (4977/10,625) was collected in the urban environment. Conclusions The species composition of the mosquito populations depended on the type of environment, with fewer species in environments with a high human impact such as urban areas and rice fields. Due to the diversity and abundance of the mosquito vectors, the human populations of all of the environments examined are considered to be at potential risk of mosquito-borne diseases. Graphical Abstract

Molecular hydrogen (H2) is crucial for agricultural microbial systems. However, the mechanisms underlying its influence on crop yields is yet to be fully elucidated. This study observed that H2-based irrigation significantly increased strawberry (Fragaria × ananassa Duch.) yield with/without nutrient fertilization. The reduction in soil available nitrogen (N), phosphorus (P), potassium (K), and organic matter was consistent with the increased expression levels of N/P/K-absorption-related genes in root tissues at the fruiting stage. Metagenomics profiling showed the alterations in rhizosphere microbial community composition achieved by H2, particularly under the conditions without fertilizers. These included the enrichment of plant-growth-promoting rhizobacteria, such as Burkholderia, Pseudomonas, and Cupriavidus genera. Rhizobacteria with the capability to oxidize H2 (group 2a [NiFe] hydrogenase) were also enriched. Consistently, genes related to soil carbon (C) fixation (i.e., rbcL, porD, frdAB, etc.), dissimilar nitrate reduction (i.e., napAB and nrfAH), and P solublization, mineralization, and transportation (i.e., ppx-gppA, appA, and ugpABCE) exhibited higher abundance. Contrary tendencies were observed in the soil C degradation and N denitrification genes. Together, these results clearly indicate that microbe-mediated soil C, N, and P cycles might be functionally altered by H2, thus increasing plant nutrient uptake capacity and horticultural crop yield.

Abstract The World Health Organization’s (WHO) World Hand Hygiene Day continues to “bring people together and accelerate hand hygiene action at the point of care in health care to contribute to a reduction in health care-associated infections and the achievement of safer, quality health care for all”.

Abstract Background Few studies have investigated how the effectiveness of hand washing in removing hand contaminants is influenced by the performance and duration of each step involved. We conducted an observational study by recruiting participants from a university campus, with the aim to comprehensively evaluate how performance, duration and demographic factors influence hand washing effectiveness. Methods A total of 744 videos were collected from 664 participants in July-October 2022 and independently evaluated by two infection control experts through labelling videos for correct and incorrect performance of each step. The individual hand washing effectiveness was determined by quantifying the percentage of residual fluorescent gel on the dorsum and palm areas of each participant’s hands. A logistic regression analysis was conducted to identify factors that were significantly associated with better hand washing effectiveness. An exposure-response relationship was constructed to identify optimal durations for each step. Approximately 2300 hand images were processed using advanced normalization algorithms and overlaid to visualize the areas with more fluorescence residuals after hand washing. Results Step 3 (rub between fingers) was the most frequently omitted step and step 4 (rub the dorsum of fingers) was the most frequently incorrectly performed step. After adjustment for covariates, sex, performance of step 4 and step 7 (rub wrists), rubbing hands during rinsing, and rinsing time were significantly associated with hand washing effectiveness. The optimal overall hand washing time was 31 s from step 1 to step 7, and 28 s from step 1 to step 6, with each step ideally lasting 4–5 s, except step 3. The palms of both hands had less fluorescence residuals than the dorsums. The areas where residuals most likely appeared were wrists, followed by finger tips, finger webs and thumbs. Conclusions Performance and duration of some hand washing steps, sex and rinsing time were associated with hand washing effectiveness. The optimal duration might be applied to all seven steps to achieve the best decontamination results. Further studies are needed to refine hand hygiene standards and enhance compliance.

Abstract Quantitative biomarkers of facial skin ageing were studied from one hundred healthy Caucasian female volunteers, aged 20–70 years, using in vivo 3D Line-field Confocal Optical Coherence Tomography (LC-OCT) imaging coupled with Artificial Intelligence (AI)-based quantification algorithms. Layer metrics, i.e. stratum corneum thickness (SC), viable epidermal thickness and Dermal–Epidermal Junction (DEJ) undulation, as well as cellular metrics were measured for the temple, cheekbone and mandible. For all three investigated facial areas, minimal age-related variations were observed in the thickness of the SC and viable epidermis layers. A flatter and more homogeneous epidermis (decrease in the standard deviation of the number of layers means), a less dense cellular network with fewer cells per layer (decrease in cell surface density), and larger and more heterogeneous nuclei within each layer (increase in nuclei volume and their standard deviation) were found with significant variations with age. The higher atypia scores further reflected the heterogeneity of nuclei throughout the viable epidermis. The 3D visualisation of fine structures in the skin at the micrometric resolution and the 1200 µm × 500 µm field of view achieved with LC-OCT imaging enabled to compute relevant quantitative biomarkers for a better understanding of skin biology and the ageing process in vivo.

Background: Genitourinary (GU) or gastrointestinal (GI) complications and tumor relapse can occur in the long term after radiotherapy for prostate cancer. Objective: To assess the late tolerance and relapse-free survival (RFS) in patients undergoing hypofractionated stereotactic boost therapy after external beam radiotherapy (EBRT) for intermediate-risk prostate cancer. Design, setting, and participants: Seventy-six patients with intermediate-risk prostate carcinoma between August 2010 and April 2013 were included. The first course delivered a dose of 46 Gy by conventional fractionation; the second course was a boost of 18 Gy (3 × 6 Gy) within 10 d. Outcome measurements and statistical analysis: GU and GI toxicities were evaluated as the primary outcomes. The secondary outcomes were overall survival and RFS. The cumulative incidence of toxicity was calculated using a competing-risk approach. Overall survival and RFS were estimated using the Kaplan-Meier method. Results and limitations: The median follow-up period was 88 mo (range, 81–99 mo). Sixty (79%) patients were treated with the CyberKnife and 16 (21%) using a linear accelerator. The cumulative incidences of GU and GI grade ≥2 toxicities at 120 mo were 1.4% (95% confidence interval [CI]: 0.1–6.6%) and 11.0% (95% CI: 5.1–19.4%), respectively. The overall survival and RFS rates at 8 yr were 89.1% (95% CI: 77–95%) and 76.9% (95% CI: 63.1–86.1), respectively. Conclusions: A very long follow-up showed low GU and GI toxicities after a hypofractionated stereotactic boost after EBRT for intermediate-risk prostate cancer. Dose escalation of the boost delivered by hypofractionated radiation therapy appears safe for use in future trials. Patient summary: We found low toxicity and good survival rates after a short and high-precision boost after external beam radiotherapy for intermediate-risk prostate cancer, with a long-term follow-up of 88 mo. This long-term treatment is safe and should be considered in future trials.

Abstract Background “Train-the-Trainers in hand hygiene” (TTT) is a standardized training to train infection prevention and control (IPC) practitioners with the aim to promote hand hygiene in health care according to the World Health Organization (WHO) multimodal improvement strategy. Little is known in the literature about the sustained impact of hand hygiene and IPC trainings adapted locally. The aim of this study is to describe the impact of three TTT courses conducted annually in Japan on the adoption of the WHO multimodal improvement strategy by local IPC practitioners who became a “trainer” after their first TTT participation as a “trainee”. Methods Three TTT courses were conducted annually from 2020 to 2022 in Japan. A team “TTT-Japan” composed of more than 20 IPC practitioners who completed their first TTT participation adapted the original TTT program to reflect the local healthcare context in Japan, and subsequently convened the 2nd and 3rd TTTs. Pre- and post-course evaluations and post-course satisfaction surveys of the course participants were conducted to assess improvement in knowledge on hand hygiene and perception towards the course, respectively. Attitude and practice surveys of the TTT-Japan trainers were conducted to assess their perception and experience in hand hygiene promotion. The Hand Hygiene Self-Assessment Framework (HHSAF), a validated tool created by WHO to monitor the capacity of hand hygiene promotion at facility level, was applied at TTT-Japan trainers’ facilities to compare results before and after trainers’ engagement. We applied inductive thematic analysis for qualitative analyses of open-ended survey questions of the trainers’ attitude and practice surveys, and the Wilcoxon Sign Rank test for quantitive comparisons of pre- and post-data for the surveys and HHSAF. Results 158 Japanese healthcare workers participated in three TTT courses, the majority of whom (131, 82.9%) were nurses. Twenty-seven local trainers were involved in 2nd and 3rd TTTs. The scores of pre- and post-course evaluations significantly improved after the course (P

Purpose: High-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer. Methods: Patients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed. Results: We recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p

Cells are exposed to a wide variety of internal and external stresses. Although many studies have focused on cellular responses to acute and severe stresses, little is known about how cellular systems adapt to sublethal chronic stresses. Using mammalian cells in culture, we discovered that they adapt to chronic mild stresses of up to two weeks, notably proteotoxic stresses such as heat, by increasing their size and translation, thereby scaling the amount of total protein. These adaptations render them more resilient to persistent and subsequent stresses. We demonstrate that Hsf1, well known for its role in acute stress responses, is required for the cell size increase, and that the molecular chaperone Hsp90 is essential for coupling the cell size increase to augmented translation. We term this translational reprogramming the ‘rewiring stress response’, and propose that this protective process of chronic stress adaptation contributes to the increase in size as cells get older, and that its failure promotes aging.

ABSTRACTOptimal pharmacokinetic (PK) properties of therapeutic monoclonal antibodies (mAbs) are essential to achieve the desired pharmacological benefits in patients. To accomplish this, we followed an approach comprising structure-based mAb charge engineering in conjunction with the use of relevant preclinical models to screen and select humanized candidates with PK suitable for clinical development. Murine mAb targeting TDP-43, ACI-5891, was humanized on a framework (VH1–3/VK2–30) selected based on the highest sequence homology. Since the initial humanized mAb (ACI-5891.1) presented a fast clearance in non-human primates (NHPs), reiteration of humanization on a less basic human framework (VH1-69-2/VK2–28) while retaining high sequence homology was performed. The resulting humanized variant, ACI-5891.9, presented a six-fold reduction in clearance in NHPs resulting in a significant increase in half-life. The observed reduced clearance of ACI-5891.9 was attributed not only to the overall reduction in isoelectric point (pI) by 2 units, but importantly to a more even surface potential. These data confirm the importance and contribution of surface charges to mAb disposition in vivo. Consistent low clearance of ACI-5891.9 in Tg32 mice, a human FcRn transgenic mouse model, further confirmed its utility for early assessment and prediction of human PK. These data demonstrate that mAb surface charge is an important parameter for consideration during the selection and screening of humanized candidates in addition to maintaining the other key physiochemical and target binding characteristics.

Abstract Binding antibody levels against SARS-CoV-2 have shown to be correlates of protection against infection with pre-Omicron lineages. This has been challenged by the emergence of immune-evasive variants, notably the Omicron sublineages, in an evolving immune landscape with high levels of cumulative incidence and vaccination coverage. This in turn limits the use of widely available commercial high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. Here we show that anti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an indirect correlate of protection against Omicron BA.1/BA.2 for individuals previously infected by SARS-CoV-2. Leveraging repeated serological measurements between April 2020 and December 2021 on 1083 participants of a population-based cohort in Geneva, Switzerland, and using antibody kinetic modeling, we found up to a three-fold reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave for anti-S antibody levels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a reduction in hazard among uninfected participants. These results provide reassuring insights into the continued interpretation of SARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.

Background: Children and adolescents are highly vulnerable to the impact of sustained stressors during developmentally sensitive times. We investigated how demographic characteristics intersect with socioeconomic dimensions to shape the social patterning of quality of life and mental health in children and adolescents, two years into the COVID-19 pandemic. Methods: We used data from the prospective SEROCoV-KIDS cohort study of children and adolescents living in Geneva (Switzerland, 2022). We conducted an intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy by nesting participants within 48 social strata defined by intersecting sex, age, immigrant background, parental education and financial hardship in Bayesian multilevel logistic models for poor health-related quality of life (HRQoL, measured with PedsQL) and mental health difficulties (measured with the Strengths and Difficulties Questionnaire). Results: Among participants aged 2–17 years, 240/2096 (11.5%, 95%CI 10.1–12.9) had poor HRQoL and 105/2135 (4.9%, 95%CI 4.0–5.9) had mental health difficulties. The predicted proportion of poor HRQoL ranged from 3.4% for 6–11 years old Swiss girls with highly educated parents and no financial hardship to 34.6% for 12–17 years old non-Swiss girls with highly educated parents and financial hardship. Intersectional strata involving adolescents and financial hardship showed substantially worse HRQoL than their counterparts. Between-stratum variations in the predicted frequency of mental health difficulties were limited (range 4.4%–6.5%). Conclusions: We found considerable differences in adverse outcomes across social strata. Our results suggest that, post-pandemic, interventions to address social inequities in HRQoL should focus on specific intersectional strata involving adolescents and families experiencing financial hardship, while those aiming to improve mental health should target all children and adolescents.

Abstract Healthcare environmental hygiene (HEH) has become recognized as being increasingly important for patient safety and the prevention of healthcare-associated infections. At the 2022 Healthcare Cleaning Forum at Interclean in Amsterdam, the academic lectures focused on a series of main areas of interest. These areas are indicative of some of the main trends and avenues for research in the coming years. Both industry and academia need to take steps to continue the momentum of HEH as we transition out of the acute phase of the Covid-19 pandemic. There is a need for new ways to facilitate collaboration between the academic and private sectors. The Clean Hospitals® network was presented in the context of the need for both cross-disciplinarity and evidence-based interventions in HEH. Governmental bodies have also become more involved in the field, and both the German DIN 13603 standard and the UK NHS Cleaning Standards were analyzed and compared. The challenge of environmental pathogens was explored through the example of how P. aeruginosa persists in the healthcare environment. New innovations in HEH were presented, from digitalization to tracking, and automated disinfection to antimicrobial surfaces. The need for sustainability in HEH was also explored, focusing on the burden of waste, the need for a circular economy, and trends towards increasingly local provision of goods and services. The continued focus on and expansion of these areas of HEH will result in safer patient care and contribute to better health systems.

Introduction: Arteriovenous fistula (AVF) rarely occurs in the portal venous system. Aetiologies include iatrogenic, surgical, and penetrating trauma of the abdomen. Clinical manifestations of superior mesenteric portal arteriovenous fistula (SMPAVF) are right heart failure, mesenteric ischaemia, or signs of portal hypertension. Report: The case of a 42 year old man with a history of Crohn's disease who had a delayed symptomatic mesenteric portal AVF, occurring 20 years after ileocecal resection, which was subsequently managed by endovascular approach is reported. The patient presented with post-prandial abdominal pain for almost one year, and dyspnoea New York Heart Association stage II. There were no signs of portal hypertension. Pre-operative contrast enhanced computed tomography showed a high flow SMPAVF, with a short and wide neck (9 mm × 16 mm) at the level of the last collateral of the superior mesenteric artery. It was associated with a large aneurysm of the mesenteric vein. Vascular plug embolisation (Amplatzer 18 × 18 mm, Abbott, Chicago, IL, USA) by femoral access allowed exclusion of the SMPAVF and preserved arterial flow in the distal collaterals. During follow up, the patient developed portal vein thrombosis and required therapeutic anticoagulation for six months. Discussion: In most cases, endovascular approaches are preferred in the management of SMPAVF. Endovascular approaches are based on minimally invasive techniques including embolisation (coiling or plug) and covered stenting. Vascular plug embolisation of SMPAVF is feasible and seems to be an effective technique, with the advantage of saving collaterals. Therapeutic anticoagulation should be considered post-operatively in cases with venous dilatation and reduced flow linked to exclusion of the AVF.

In eastern Australia we expect to experience wet conditions during La Niña and dry during El Niño events. We explore how well these expectations match historical outcomes by assessing, for spring, how much rain fell during past La Niña and El Niño events. We use a tercile framing and find that for rainfall averaged across eastern Australia, La Niña approximately doubles the chance of spring rainfall being in the wet tercile whereas El Niño approximately doubles the chance of a dry spring. Also of note is that during La Niña, the dry tercile is mostly vacant and during El Niño, the wet tercile is mostly vacant, indicating that one should not expect dry conditions in La Niña or wet in El Niño for eastern Australia as a whole. At individual locations across Australia, the results vary, and in some cases, including the eastern seaboard, La Niña or El Niño events do not change the odds of wet and dry springs significantly beyond chance expectations. For example, in the Sydney region, the normal chance of experiencing a wet tercile spring is 33% and this increases only slightly in a La Niña to 38%, suggesting that La Niña is not a strong indicator for wet conditions in this region. These outcomes may help to manage our expectations for the likely rainfall outcomes during future El Niño–Southern Oscillation (ENSO) events.

Abstract The highly contagious respiratory syncytial virus (RSV) is responsible for up to approximately 50,000 hospitalisations during each RSV season in children aged under 5 years in France, with the burden greatest in infants younger than 1 year who were born at term. There is a need for a strategy to universally protect young children from RSV infection, and thereby reduce the pressure that RSV places every year on RSV-infected children, their parents, and French healthcare systems. Potential strategies currently undergoing clinical investigation include passive immunisation via maternal vaccination or administration of long-acting monoclonal antibodies at or soon after birth, followed by vaccination later in infancy or childhood. An ongoing partnership and collaboration between parents, public health authorities, and frontline primary healthcare will need to be reinforced once these new RSV prevention strategies are available, to facilitate their use and ensure that all children receive adequate protection from the start of their first RSV season.

Here, the authors use an advanced data-mining method to show how “extreme modes” of large-scale climate variability, such as El Niño, can lead to devastating marine heatwaves.

Abstract Background Large-scale trials have shown that hypofractionated adjuvant breast radiotherapy was as effective in terms of survival and local control as conventional fractionated radiotherapy, and acute toxicity was reduced with hypofractionated radiotherapy. However, there is a lack of data about the toxicity of breast with regional nodal irradiation (RNI). The aim of this study was to assess the effect of fractionation on radiation-related acute skin toxicity in patients receiving RNI in addition to whole-breast or chest wall irradiation, using real-life data. Methods We conducted a prospective, multicenter cohort study with systematic computerized data collection integrated into Mosaiq®. Three comprehensive cancer centers used a standardized form to prospectively collect patient characteristics, treatment characteristics and toxicity. Results Between November 2016 and January 2022, 1727 patients were assessed; 1419 (82.2%) and 308 (17.8%) patients respectively received conventional fractionated and hypofractionated radiation therapy. Overall, the incidence of acute grade 2 or higher dermatitis was 28.4% (490 patients). Incidence was lower with hypofractionated than with conventional fractioned radiation therapy (odds ratio (OR) 0.34 [0.29;0.41]). Two prognostic factors were found to increase the risk of acute dermatitis, namely 3D (vs IMRT) and breast irradiation (vs chest wall). Conclusion Using real-life data from unselected patients with regional nodal irradiation, our findings confirm the decreased risk of dermatitis previously reported with hypofractionated radiation therapy in clinical trials. Expansion of systematic data collection systems to include additional centers as well as dosimetric data is warranted to further evaluate the short- and long-term effects of fractionation in real life.

Abstract Background Infection prevention and control (IPC) measures in Japan are facilitated by a financial incentive process at the national level, where facilities are categorized into three groups (Tier 1, Tier 2, or no financial incentive). However, its impact on IPC at the facility level using a validated tool has not been measured. Methods A nationwide cross-sectional study was conducted from August 2019 to January 2020 to evaluate the situation of IPC programs in Japan, using the global IPC Assessment Framework (IPCAF) developed by the World Health Organization. Combined with the information on the national financial incentive system, the demographics of facilities and each IPCAF item were descriptively analyzed. IPCAF scores were analyzed according to the facility level of care and the national financial incentive system for IPC facility status, using Dunn-Bonferroni and Mann–Whitney U tests. Results Fifty-nine facilities in Japan responded to the IPCAF survey: 34 private facilities (57.6%) and 25 public facilities (42.4%). Of these, 11 (18.6%), 29 (49.2%), and 19 (32.3%) were primary, secondary, and tertiary care facilities, respectively. According to the national financial incentive system for IPC, 45 (76.3%), 11 (18.6%), and three (5.1%) facilities were categorized as Tier 1, Tier 2, and no financial incentive system, respectively. Based on the IPCAF total score, more than half of the facilities were categorized as “Advanced” (n = 31, 55.3%), followed by “Intermediate” (n = 21, 37.5%). The IPCAF total score increased as the facility level of care increased, while no statistically significant difference was identified between the secondary and tertiary care facilities (p = 0.79). There was a significant difference between Tier 1 and Tier 2 for all core components and total scores. Core components 5 (multimodal strategies for implementation of IPC interventions) and 6 (monitoring/audit of IPC and feedback) were characteristically low in Japan with a median score of 65.0 (interquartile range 40.0–85.0) and 67.5 (interquartile range 52.5–87.5), respectively. Conclusions The national financial incentive system was associated with IPC programs at facility level in Japan. The current financial incentive system does not emphasize the multimodal strategy or cover monitoring/audit, and an additional systematic approach may be required to further promote IPC for more practical healthcare-associated infection prevention.