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Summary: Two recombinases, RAD51 and DMC1, catalyze meiotic break repair to ensure crossovers (COs) between homologous chromosomes (interhomolog) rather than between sisters (intersister). FIDGETIN‐LIKE‐1 (FIGL1) downregulates both recombinases. However, the understanding of how FIGL1 functions in meiotic repair remains limited. Here, we discover new genetic interactions of Arabidopsis thaliana FIGL1 that are important in vivo determinants of meiotic repair outcome.In figl1 mutants, compromising RAD51‐dependent repair, either through the loss of RAD51 paralogs (RAD51B or XRCC2) or RAD54 or by inhibiting RAD51 catalytic activity, results in either unrepaired breaks or meiotic CO defects. Further, XRCC2 physically interacts with FIGL1 and partially counteracts FIGL1 activity for RAD51 focus formation. Our data indicate that RAD51‐mediated repair mechanisms compensate FIGL1 dysfunction.FIGL1 is not necessary for intersister repair in dmc1 but is essential for the completion of meiotic repair in mutants such as asy1 that have impaired DMC1 functions and interhomolog bias. We show that FIGL1 attenuates interhomolog repair, and ASY1 counteracts FIGL1 to promote interhomolog recombination.Altogether, this study underlines that multiple factors can counteract FIGL1 activity to promote accurate meiotic repair. [ABSTRACT FROM AUTHOR]

Objective: Mental health lived experience organizations (LEOs) and their lived experience workforce are increasingly recognized as invaluable. However, a deeper understanding of the elements that enhance or inhibit LEOs' efficacy is required to learn how to sustain LEOs and support their workforce. Rapid international expansion has resulted in significant LEO growth and change, challenging many LEOs to adapt. With this rapid expansion, the field is evolving faster than many LEOs can keep pace with. This review, codesigned and coproduced in partnership with a LEO to draw on both lived experience and academic perspectives, aims for a deeper understanding of which elements within a LEO enhance or inhibit its efficacy, growth, and support for its lived experience workforce. Methods: A systematic search of peer-reviewed and non–peer-reviewed literature, following the PRISMA-ScR guidelines and JBI methodology, identified 60 records published in English between 2000 and 2022. Results: The results indicate general agreement regarding which LEO elements are important (e.g., culture, leadership, board composition, organizational structure, financial arrangements, and professionalization). However, considerable disagreements exist regarding the relative influence of several of these elements, especially funding arrangements, in which funder and LEO values often diverge; training for increased lived experience professionalization; and partnerships with medical model–focused mental health services. Conclusions: Organizational disagreements relate to managing future LEO growth and advancing the lived experience workforce while preserving LEOs' unique characteristics that make them valued mental health services. Further research should examine community differences among LEOs, including hybrid LEOs within services and non-LEO mental health organizations. [ABSTRACT FROM AUTHOR]

This research shows that cationic polyacrylamide (CPAM) flocculants, widely used in wastewater treatment, are susceptible to degradation when in contact with various metallic surfaces. This is evidenced by the investigation of the evolution of CPAM's rheological properties during degradation within metallic Couette tools, observing a transition from elastic to viscous behavior. The degradation is clearly evident on various metallic surfaces, while thermoplastic surfaces have significantly less effect on CPAM degradation. Key findings indicate that chemical interactions, rather than mechanical stress, are the primary cause of degradation, and this reaction is activated by temperature. Techniques such as Fourier Transform Infrared spectroscopy, Nuclear Magnetic Resonance analysis, and polyelectrolyte titration provided some initial understanding of this mechanism. This research offers valuable insights into CPAM's interactions with metal surfaces, with important implications for environmental and industrial applications, and establishes the appropriate protocol for characterizing the intrinsic rheological properties of these materials. [ABSTRACT FROM AUTHOR]

Diverse microbial communities play a crucial role in maintaining the proper functioning of river ecosystems and are considered important indicators of river water quality. Although the Seine River being heavily impacted by human activities, little is known about the microbial communities in its surface waters. In order to monitor water quality and promote sustainable use, we studied its microbial diversity using high-throughput sequencing technology, and explored their relationships with physico-chemical properties. The dominant phyla identified were Proteobacteria, Actinobacteriota, Bacteriodota, and Cyanobacteria. The presence of the Alphaproteobacteria and Gammaproteobacteria indicates that the Seine River water nutrient profile is mainly determined by the recalcitrant organic compounds present in WWTP effluents. Bacterial diversity showed significant temporal variability with a highly significant difference in bacterial composition between 2020 and 2021, probably due to variations in water flow favoring Cyanobacteria growth. Summer displayed higher microbial activity and abundance than autumn, attributed to temperature and orthophosphate content. Spatial variation in bacterial composition was observed between sites upstream and downstream of Paris, as well as before and after of the Seine Valenton-WWTP, subject to an accumulation phenomenon and impacted by wastewater treatment. Further assessment of emerging contaminants and other pollutants is required to better understand these variations. These results provide a basic understanding of the microbial community in the Seine River, serving as a reference for assessing the impact of implementing new wastewater disinfection techniques in the near future. [ABSTRACT FROM AUTHOR]

Introduction: Total nephrectomies for the treatment of Wilms' tumor (WT) are more and more performed by laparoscopy, although indications for this approach following the UMBRELLA guidelines are currently very restrictive. The purpose of this study was to assess the compliance to the criteria of the UMBRELLA protocol for minimally invasive approach of WT. Methods: This retrospective multicenter study included children operated on by laparoscopic total nephrectomy for suspected WT before 2020. Imaging was reviewed centrally. Results: Fifty-six patients (50 WT and 6 nephrogenic rests) were operated on at a median age of 3.3 ± 2.6 years. Thirteen (23%) patients had metastasis at diagnosis. The mean operative time was 213 ± 84 min. There were eight (14.3%) conversions and five peroperative complications. A local stage III was confirmed in seven (12.5%) cases, including two for tumor rupture. Only one (1.8%) of the procedures followed the SIOP-UMBRELLA indications for laparoscopy. The criterion "ring of normal parenchyma" was met only once. Conservative surgery seemed possible in ten (17.9%) cases. The extension of the tumor beyond the ipsilateral edge of the vertebra after chemotherapy and a volume over 200 mL were associated with an increased risk of conversion (p = 0.0004 and p = 0.001 respectively). After a mean follow-up of 5.2 ± 4.0 years, although there was no local recurrence, one death occurred due to metastatic progression at 15 months postoperatively. Conclusions: The laparoscopic approach of WT beyond the UMBRELLA recommendations was feasible with low risk of local recurrence. Its indications may be updated and validated. [ABSTRACT FROM AUTHOR]

Purpose: Evidence on treatment preferences of patients with moderate-to-severe atopic dermatitis (AD) in the United States (US) is limited and an assessment of treatment preferences in this group is warranted. Materials and methods: An online discrete choice experiment survey was conducted (June 2023) among US adults with self-reported moderate-to-severe AD or experience with systemic therapy who had inadequate response to topical treatments. Preference weights estimated from conditional logistic regression models were used to calculate willingness to trade off and attributes’ relative importance (RI). Results: Participants (N=300; mean age: 45years; 70% females; 52% systemic therapy experienced) preferred treatments with higher efficacy, lower risk of adverse events (AEs), and less frequent blood tests (p<.05). Treatment attributes, from high to low RI, were itch control (38%), risk of cancer (23%), risk of respiratory infections (18%), risk of heart problems (11%), sustained improvement in skin appearance (5%), blood test frequency (3%), and frequency and mode of administration (2%); together, AE attributes accounted for more than half of the RI. Conclusions: Participants preferred AD treatments that maximize itch control while minimizing AE risks, whereas mode of administration had little impact on preferences. Understanding patients’ preferences may help improve shared decision-making, potentially leading to enhanced patient satisfaction with treatment, increased engagement, and better clinical outcomes. [ABSTRACT FROM AUTHOR]

Advanced genomic technologies such as whole exome or whole genome sequencing have improved diagnoses and disease outcomes for individuals with genetic diseases. Yet, variants of unknown significance (VUS) require rigorous validation to establish disease causality or modification, or to exclude them from further analysis. Here, we describe a young individual of Polynesian ancestry who in the first 13 mo of life presented with SARS-CoV-2 pneumonia, severe enterovirus meningitis and adenovirus gastroenteritis, and severe adverse reaction to MMR vaccination. Genomic analysis identified a previously reported pathogenic homozygous variant in IFNAR1 (c.1156G > T, p.Glu386* LOF), which is common in Western Polynesia. Moreover, a new and putatively deleterious canonical splice site variant in DOCK8 was also found in homozygosity (c.3234 + 2T > C). This DOCK8 variant is common in Polynesians and other under-represented ancestries in large genomic databases. Despite in silico bioinformatic predictions, extensive in vitro and ex vivo analysis revealed the DOCK8 variant likely be neutral. Thus, our study reports a novel case of IFNAR1 deficiency, but also highlights the importance of functional validation of VUS, including those predicted to be deleterious, and the pressing need to expand our knowledge of the genomic architecture and landscape of under-represented populations and ancestries. [ABSTRACT FROM AUTHOR]

Human Research Ethics Committee (HREC) reviewers often provide similar feedback across applications, which suggests that the problem lies in researcher awareness of key issues rather than novel, unsolvable challenges. If common problems can be addressed before lodgement by applicants referencing clear evidence-based supports (e.g., FAQs on common application shortcomings), it would improve efficiency for HREC members and expedite approvals. We aim to inform such supports by analysing the patterns in the most frequent feedback made by HREC members during review processes. We collected every instance (N = 4,195) of feedback made on N = 197 'low-risk' protocols by all HREC staff (N = 16) at one institution over the course of a full year (2019). Reflexive thematic analysis to identify themes (and content analysis to determine relative frequency) revealed that the top three themes are consistent with existing literature: Consent, Administrative, and Methodological concerns. However, we identified important new themes that are not captured in previous research, including 'Risk to Researchers', 'Commercial benefit, scope and scale', 'Diversity' (covering issues of cultural sensitivity, language and accessibility), as well as fair right to a complaints process. Our thorough exploration of information-rich primary data marks an important methodological improvement over previous studies and offers a theoretical contribution to understanding themes that have heretofore been overlooked in the ethics review process. By identifying the common challenges experienced in HREC review we can better inform tailored supports to applicants (by extension reducing workload burdens on HREC systems) and reduce their perceived barriers to engaging in challenging but meaningful research. [ABSTRACT FROM AUTHOR]

In this study, we disclose for the first time that formate salt can be used as a bifunctional reagent for the synthesis of phenol derivatives and as a CO source for carbonylative cross‐coupling processes using the COware gas reactor under activation free conditions. Key to this success is the in‐situ synthesis of aryl formate via an unprecedented nickel/organophotocatalyst system under blue LED irradiation. This developed system demonstrated high applicability to various aryl iodide substrates for synthesizing phenol derivatives. Moreover, the generated CO could be utilized in a range of carbonylative C‐heteroatom and C−C processes. Notably, commercially available H13COONa salt can serve as a bifunctional reagent for both synthesizing phenols and generating 13CO. [ABSTRACT FROM AUTHOR]

Detection of botulinum neurotoxins (BoNTs) involves a combination of technical challenges that call for the execution of inter-laboratory proficiency tests (PTs) to define the performance and ease of implementation of existing diagnostic methods regarding representative BoNT toxin-types spiked in clinical, food, or environmental matrices. In the framework of the EU project EuroBioTox, we organized an international proficiency test for the detection and quantification of the clinically relevant BoNT/A, B, E, and F sero- and subtypes including concentrations as low as 0.5 ng/mL. BoNTs were spiked in serum, milk, and soil matrices. Here, we evaluate the results of 18 laboratories participating in this PT. Participants have implemented a wide array of detection methods based on functional, immunological, and mass spectrometric principles. Methods implemented in this proficiency test notably included endopeptidase assays either coupled to mass spectrometry (Endopep-MS) or enzyme-linked immunosorbent assays (Endopep-ELISA). This interlaboratory exercise pinpoints the most effective and complementary methods shared by the greatest number of participants, also highlighting the importance of combining the training of selected methods and of distributing toxin reference material to reduce the variability of quantitative data. [ABSTRACT FROM AUTHOR]

Asymptomatic carriers of Plasmodium falciparum represent important parasite reservoirs maintaining malaria transmission in the community. This study aimed on the one hand to screen the other household members living with children under seasonal malaria chemoprevention (SMC) coverage in order to determine the level of malaria infection in this population and on the other hand to determine the appropriate type of rapid diagnostic test (RDT) for this screening to detect these asymptomatic carriers in the community. During the 2022 SMC campaign (July to October), a cross-sectional survey was carried out in 745 participants who were screened by ultrasensitive rapid diagnostic test (usRDT), standard rapid diagnostic test (rRDT) and microscopy. Out of them, 395 had microscopy results available and were included in the data analysis. The prevalence of asymptomatic carriers of asexual forms of Plasmodium falciparum was 26.58% (105/395) while sexual forms were found in 5.32% (21/395) of the study population. Children from 5 to 15 years had the highest prevalence of P. falciparum asexual forms 35.76% (59/165) compared with older participants. Malaria positivity rate for rRDT and usRDT was 29.40% (219/745) and 40.49% (305/745) respectively. The usRDT had a higher sensitivity than the rRDT (72.38% (95% CI 62.8–80.66) vs. 60.95% (95% CI 50.94–70.33)). In terms of specificity, rRDT had a higher specificity 82.41% (95% CI 77.53–86.62) versus 69.66% (95% CI 64.01–74.89) for usRDT. This study reports a high prevalence of parasite carriers in household members of children under SMC coverage in Nanoro, Burkina Faso. In conclusion, usRDT seems more appropriate for strategies based on detection and treatment of parasite carriers within the community. [ABSTRACT FROM AUTHOR]

Background: There is established evidence of complicated grief among people with an intellectual disability. This paper describes the process of adapting complicated grief therapy (CGT) for this population. Method: Action research documented the adaptation of CGT. Qualitative methods included analysing meeting notes, reflective interviews with two members of the team involved in adapting the materials, and interviews with six professionals working in disability settings who reviewed the adapted materials. Results: Key processes included adapting the standardised tools that form part of CGT and developing adapted approaches to abstract concepts related to death, dying and bereavement. Key therapeutic components such as imaginal revisiting and the role of significant others required adaptation for implementation with people with intellectual disabilities. Conclusion: The importance of adapting evidence‐based therapies for people with intellectual disabilities is emphasised. This research provides an adapted form of an established therapy for piloting with this population. [ABSTRACT FROM AUTHOR]

Introduction: Faced to the growing development of collecting systematic molecular analyses in relapsed pediatric cancers to transform their targeted matched therapies, this study aimed to assess the clinical and therapeutic indications of systematic diagnostic genomic explorations performed in pediatric solid cancers to determine which type of screening and if it afford at relapse time an accurate targeted strategy. Methods: A total of 280 patients less than 22 years, referred at the University Hospitals of Strasbourg for a newly diagnosed solid tumor from January 2015 to December 2021, were prospectively genomically investigated since diagnosis. Using 7 different molecular tests going from single-gene methods (IHC, FISH, RT-PCR, Sanger sequencing, droplet digital PCR) to largescale analyses (Next-Generation sequencing, RNAsequencing and FoundationOne®CDx), we explored retrospectively the molecular findings in those pediatric solid tumors (except hematolymphoid cancers) to improve diagnosis, prognosis assessment and relapse therapeutics. Results: One hundred and ninety-eight patients (71%) underwent molecular biology (MB) at diagnosis. Thirty-eight different histologies were grouped into cerebral tumors (30%), sarcomas (26%, bone and soft tissues), various blastomas (27%), and other entities (17%). Over a median 40-month follow-up, the overall survival rate of patients was 85% and the relapse rate 28%. Of the 326 analyses carried out, 245 abnormalities (single nucleotide variations: 50%, fusions: 25%, copy number alteration: 20%) concerning 70 oncogenes were highlighted. The overall clinical impact rate was 84%. Broad-spectrum analyses had a higher therapeutic impact (57%) than the targeted analyses (28%). 75% of broad-spectrum tests found an actionable variant conducting 23% of patients to receive rapidly a matched targeted therapy since first relapse. Conclusion: Our experience highlighted the clinical utility of molecular profiling of solid tumors as soon as at diagnosis in children to expect improving access to innovative agents at relapse. [ABSTRACT FROM AUTHOR]

Poorly-treated wastewater harbors harmful microorganisms, posing risks to both the environment and public health. To mitigate this, it is essential to implement robust disinfection techniques in wastewater treatment plants. The use of performic acid (PFA) oxidation has emerged as a promising alternative, due to its powerful disinfection properties and minimal environmental footprint. While PFA has been used to inactivate certain microbial indicators, its potential to tackle the entire microbial community in effluents, particularly resistant bacterial strains, remains largely unexplored. The present study evaluates the efficacy of PFA disinfection on the microbial communities of a WWTP effluent, through microbial resistance mechanisms due to their membrane structure. The effluent microbiome was quantified and identified. The results showed that the number of damaged cells increases with CT, reaching a maximum for CT = 240 mg/L•min and plateauing around 60 mg/L•min, highlighting the optimal conditions for PFA-disinfection against microbial viability. A low PFA level with a 10-min contact time significantly affected the microbial composition. It is worth noting the sensitivity of several bacterial genera such as Flavobacterium, Pedobacter, Massilia, Exiguobacterium, and Sphingorhabdus to PFA, while others, Acinetobacter, Leucobacter, Thiothrix, Paracoccus, and Cloacibacterium, showed resistance. The results detail the resistance and sensitivity of bacterial groups to PFA, correlated with their Gram-positive or Gram-negative membrane structure. These results underline PFA effectiveness in reducing microbial levels and remodeling bacterial composition, even with minimal concentrations and short contact times, demonstrating its suitability for widespread application in WWTPs. [ABSTRACT FROM AUTHOR]

Healthy ageing, which is the target of life' s later developmental stage, can be achieved through building a wise perspective towards life and existence. However, it may not be achievable for older people when the societal sources are limited. The TILDA project aimed to evaluate the associated factors with healthy ageing and to transfer that knowledge into practice. Hence, determining the perspectives of older people support and advocacy organisations on the enablers and facilitators of the healthy ageing strategies of TILDA is essential to gain a better understanding of the project and plan future strategies. This study aimed to investigate how the TILDA project has influenced or impacted upon these organisations from education, policy, or practice perspectives. The participants (n = 15) included in the study's sample were reached through representative organisations acting to support older people in the Republic of Ireland. Semi-structured interviews were conducted online via Zoom. A systematic thematic data analysis procedure was followed, and three themes emerged from the qualitative data, revealing the perceptions of participants about the TILDA project: (1) Limitations of TILDA, (2) Contributions of TILDA, and (3) Future recommendations for TILDA. In conclusion, among the disadvantages of TILDA, the most significant is not being representative and visible enough; it is evident that it is pivotal to develop a more inclusive culture of TILDA with close cooperation and effective marketing strategies. It is also apparent that TILDA has several advantages that include providing insights into ageing and rich data to plan future support for older people. [ABSTRACT FROM AUTHOR]

Purpose: Peripheral nerve stimulation (PNS) limits the usability of state‐of‐the‐art whole‐body and head‐only MRI gradient coils. We used detailed electromagnetic and neurodynamic modeling to set an explicit PNS constraint during the design of a whole‐body gradient coil and constructed it to compare the predicted and experimentally measured PNS thresholds to those of a matched design without PNS constraints. Methods: We designed, constructed, and tested two actively shielded whole‐body Y‐axis gradient coil winding patterns: YG1 is a conventional symmetric design without PNS‐optimization, whereas YG2's design used an additional constraint on the allowable PNS threshold in the head‐imaging landmark, yielding an asymmetric winding pattern. We measured PNS thresholds in 18 healthy subjects at five landmark positions (head, cardiac, abdominal, pelvic, and knee). Results: The PNS‐optimized design YG2 achieved 46% higher average experimental thresholds for a head‐imaging landmark than YG1 while incurring a 15% inductance penalty. For cardiac, pelvic, and knee imaging landmarks, the PNS thresholds increased between +22% and +35%. For abdominal imaging, PNS thresholds did not change significantly between YG1 and YG2 (−3.6%). The agreement between predicted and experimental PNS thresholds was within 11.4% normalized root mean square error for both coils and all landmarks. The PNS model also produced plausible predictions of the stimulation sites when compared to the sites of perception reported by the subjects. Conclusion: The PNS‐optimization improved the PNS thresholds for the target scan landmark as well as most other studied landmarks, potentially yielding a significant improvement in image encoding performance that can be safely used in humans. [ABSTRACT FROM AUTHOR]

Purpose: We propose and evaluate multiphoton parallel transmission (MP‐pTx) to mitigate flip angle inhomogeneities in high‐field MRI. MP‐pTx is an excitation method that utilizes a single, conventional birdcage coil supplemented with low‐frequency (kHz) irradiation from a multichannel shim array and/or gradient channels. SAR analysis is simplified to that of a conventional birdcage coil, because only the radiofrequency (RF) field from the birdcage coil produces significant SAR. Methods: MP‐pTx employs an off‐resonance RF pulse from a conventional birdcage coil supplemented with oscillating z$$ z $$‐directed fields from a multichannel shim array and/or the gradient coils. We simulate the ability of MP‐pTx to create uniform nonselective brain excitations at 7 T using realistic B1+$$ {\mathrm{B}}_1^{+} $$ and ΔB0$$ \Delta {\mathrm{B}}_0 $$ field maps. The RF, shim array, and gradient waveform's amplitudes and phases are optimized using a genetic algorithm followed by sequential quadratic programming. Results: A 1 ms MP‐pTx excitation using a 32‐channel shim array with current constrained to less than 50 Amp‐turns reduced the transverse magnetization's normalized root‐mean‐squared error from 29% for a conventional birdcage excitation to 6.6% and was nearly 40% better than a 1 ms birdcage coil 5 kT‐point excitation with optimized kT‐point locations and comparable pulse power. Conclusion: The MP‐pTx method resembles conventional pTx in its goals and approach but replaces the parallel RF channels with cheaper, low‐frequency shim channels. The method mitigates high‐field flip angle inhomogeneities to a level better than 3 T CP‐mode and comparable to 7 T pTx while retaining the straightforward SAR characteristics of conventional birdcage excitations, as low‐frequency shim array fields produce negligible SAR. [ABSTRACT FROM AUTHOR]

Fluorinated, manganese‐redox cation‐disordered rocksalts are promising candidates for high‐performance cobalt‐free Li‐ion cathode active material. A need for reactive fluorinated precursors was however identified. While manganese oxyfluorides are promising precursor candidates, none stable at room temperature was reported prior to 2023. The key to their recent synthesis by reacting molecular fluorine with MnO was a procedure to continuously scan the temperature axis in search of activation temperatures. In line with this philosophy of continuous exploration of the chemical space, two experimental procedures are reported to scan the stoichiometry axis of a gas‐solid phase diagram in search of transitions and intermediate compounds. Their application to F2 ‐ Mn3O4 and F2 ‐ Mn2O3 phase diagrams resulted in the discovery of two new ranges of stable manganese oxyfluorides of respective compositions MnO1.33‐0.13xFx with x<0.5 and MnO1.5‐0.22xFx with x<1. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease (DED) is one of the most prevalent eye conditions worldwide, with artificial tears serving as a primary treatment option. Despite their wide availability on the European market, there is a lack of established classifications based on their physicochemical properties. The aim of our study was therefore (i) to develop an analytical method that measures the concentration and the molecular weight (MW) of the hyaluronic acid (HA) in commercialized products, and (ii) to propose an overview based on their various physicochemical parameters. Methods: The intrinsic viscosity and MW of the HA, as well as osmolarity, pH, rheological profile, and viscosity, were measured or determined. A specific method was developed to measure the average intrinsic viscosity and HA content using a liquid size-exclusion chromatography system. The MW was determined using the Mark–Houwink equation. Results: Thirty-seven products commercialized in Europe were analyzed, with 21 of them containing HA. The HA MW was lowest (300 kDa) for Thealose®, Thealoz Duo® Gel, and Hyabak®, and highest (1300 kDa) for Vismed® Multi, Vismed® Gel, and Neovis® Gel. The pH values varied between 5.94 for Treovis® and 8.06 for Systane® Ultra. Osmolarity ranged between 148 mOsm/L and 325 mOsm/L for Neovis® and Treovis®, respectively. Viscosity was highly variable, ranging from 0.38 mPas·s for Hylolipid® to 337.47 mPas·s for Thealoz® Duo Gel. Finally, rheological profile analysis revealed different shear-thinning behaviors. Conclusion: While the perfect eye drop does not exist, a multitude of options are available to choose from. This study improves our understanding of the major tear substitutes available on the European market based on several physicochemical properties. A better understanding and awareness of these parameters is crucial in order to offer the best treatment for patients with DED. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study is to assess the real-life efficacy and tolerance of a new preservative-free, surfactant-free latanoprost (PFSF-LAT) formulation. Methods: Retrospective, multicentre, non-comparative, observational study in patients with ocular hypertension or open angle glaucoma, naïve or non-naïve to previous intraocular pressure (IOP)-lowering treatment, and treated for at least 3 months with the study eye drop. IOP for worse eye, ocular signs and symptoms, and concomitant use of artificial tears were collected at study drug initiation and at last visit under treatment. Reasons for discontinuing the study eye drop (if relevant) and investigators' satisfaction were also assessed. Results: In the per protocol population (103 eyes; 63 naïve, 39 switched, 1 not classified because of missing data), IOP decreased significantly (p < 0.001) from 21.6 ± 5.0 mmHg at baseline to 16.1 ± 3.5 mmHg at the end of the study (mean reduction of − 5.5 ± 4.6 mmHg; − 25.5%). IOP in naïve patients was significantly improved, with a mean reduction of 7.1 mmHg (− 30.7%), which was within expected latanoprost IOP-lowering effect. Interestingly, in previously treated patients, switching to PFSF-LAT also allowed for a further 2.9 mmHg decrease in IOP (p < 0.001). The incidence of ocular side effects at study initiation was significantly (p < 0.001) reduced from 31.1% to 11.3% in the overall population, and from 65.0% to 7.5% in switched patients. This included conjunctival hyperaemia and superficial punctate keratitis (from 42.5% to 2.5% and from 37.5% to 2.5% in switched patients, respectively). According to investigators, tolerance and efficacy of the study eye drop were satisfactory or very satisfactory in 98.1% and 83.2% of patients, respectively. Conclusion: PFSF-LAT is an efficient treatment for patients with glaucoma with an improved tolerance profile. It can be considered as initial therapy in naïve patients or in patients with poor ocular tolerance to previous IOP-lowering eye drops. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is a congenital condition characterized by a third copy of chromosome 21, resulting in a unique phenotype, physical, and intellectual development delays and multisystem health effects. Swimming is a commonly recommended exercise mode for individuals with DS because it has been shown to confer cardiovascular, neuromuscular, and psychological benefits. Local and international organizations offer athletes with DS opportunities to compete in swimming. Swimming athletes with DS benefit from individualized resistance training (RT) delivered by qualified strength and conditioning (S&C) practitioners. The purpose of this article is to provide the S&C practitioner with a needsdriven framework for RT program design with recommendations relevant to potential orthopedic, systemic, and sensorimotor considerations of swimming athletes with DS. Programming and periodization strategies are proposed for maximizing the effectiveness of dry-land RT for this population. [ABSTRACT FROM AUTHOR]

In this study, we report a biological temperature-sensing electrical regulator in the cytochrome c oxidase of the Devil Worm, Halicephalobus mephisto. This extremophile metazoan was isolated 1.3 km underground in a South African goldmine, where it adapted to heat and potentially to hypoxia, making its mitochondrial sequence a likely target of adaptational change. We obtained the complete mitochondrial genome sequence of this organism and show through dN/dS analysis evidence of positive selection in H. mephisto cytochrome c oxidase subunits. Seventeen of these positively selected amino acid substitutions were located in proximity to the H- and K-pathway proton channels of the complex. Surprisingly, the H. mephisto cytochrome c oxidase completely shuts down at low temperatures (20 °C), leading to a 4.8-fold reduction in the transmembrane proton gradient (ΔΨm) compared to optimal temperature (37 °C). Direct measurement of oxygen consumption found a corresponding 4.6-fold drop at 20 °C compared to 37 °C. Correspondingly, the lifecycle of H. mephisto takes four times longer at low temperature than at higher. This elegant evolutionary adaptation creates a finely-tuned mitochondrial temperature sensor, allowing this ectothermic organism to maximize its reproductive success across varying environmental temperatures. Here, an evolutionary adaptation converting mitochondrial respiration into a thermometer is reported. The adaptive changes center around the proton channels of cytochrome c oxidase. [ABSTRACT FROM AUTHOR]

Background and Aims Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297). Methods MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH. Results Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio.74, 95% confidence interval.66–.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio.85, 95% confidence interval.74–.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality. Conclusions Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care. [ABSTRACT FROM AUTHOR]

Background: Psychological interventions delivered in inpatient settings have rarely been coproduced with those who receive them. The aim of this study is to outline the coproduction process which led to the development of an adapted inpatient intervention underpinned by a Cognitive Behaviour Therapy for psychosis model. Method: Our coproduction group was comprised of experts by experience, family and carers, multi-disciplinary clinicians, and researchers. The group met monthly to develop the intervention and focused on eight key areas of the intervention, including therapist values, assessment, formulation, coping strategies, crisis/safety plans, and discharge plans. Results: The coproduction panel highlighted the importance of flexible delivery of the intervention, developing a trusting relationship with the therapist, advocacy, prioritising patient safety on the ward, managing the impacts of inpatient care, preparing for discharge, and having family, carer and community involvement. Challenges of the coproduction process included having a pre-existing intervention model that was being adapted rather than coproducing a new one, discussing emotionally charged issues, and having limited time to coproduce the intervention. Discussion: Coproduction brought immense value to the development of this intervention, ensuring it was culturally competent and suitable for the inpatient setting. Further research should be undertaken exploring the coproduction process applied to clinical research. [ABSTRACT FROM AUTHOR]

Laboratory experiments suggest that the evolution of in-plane shear rupture along an interface separating two elastic blocks typically shows a transition from slow to fast slip. In contrast to the commonly used continuum mechanics-based approaches, here we study the shear rupture process along a weak interface using the discontinuous deformation analysis (DDA) method. We incorporate a slip-weakening constitutive friction law to simulate the initiation and propagation of shear rupture under external conditions of a constant normal load and a steadily increased shear load. As the shear load increases, our modeling results reveal a sharp transition from episodic expansion and arrest to unstable runaway rupture, consistent with previous experimental results. In the stage of dynamic runaway, rupture velocity is limited by the Rayleigh wave velocity. We further investigate the effects of external loading conditions including load point velocity and normal stress on rupture behavior. We find that the dynamic rupture velocity increases with load point velocity and normal stress, also consistent with previous studies. Our results indicate that the DDA method can well capture some of the general characteristics of shear rupture process and, hence, can be applied to study other aspects of dynamic shear ruptures. Highlights: The slip-weakening friction law is incorporated into DDA to simulate shear rupture processes along a weak interface. Under the DDA model, rupture evolution is characterized by episodic expansion and arrest, followed by a sharp transition to dynamic runaway. The DDA model reproduces a suite of shear rupture behavior, consistent with previous studies. [ABSTRACT FROM AUTHOR]

Formulations designed to address ocular conditions and diseases are predominantly administered topically. While in vitro test systems have been developed to assess corneal permeation under extended contact conditions, methods focusing on determining the penetration depth and kinetics of a substance within the cornea itself rather than through it, are scarce. This study introduces a method for time-dependent penetration depth analysis (10 and 60 min) by means of a semiquantitative imaging method in comparison with a quantitative corneal depth-cut technique, employing fluorescein sodium at concentrations of 0.2 and 0.4 mg/mL as a small molecule model substance and sheep cornea as a human surrogate. Excised tissues exhibited sustained viability in modified artificial aqueous humor and maintained thickness (746 ± 43 µm) and integrity (electrical resistance 488 ± 218 Ω∙cm2) under the experimental conditions. Both methods effectively demonstrated the expected concentration- and time-dependent depth of penetration of fluorescein sodium, displaying a significantly strong correlation. The traceability of the kinetic processes was validated with polysorbate 80, which acted as a penetration enhancer. Furthermore, the imaging-based method enabled detecting the retention of larger structures, such as hyaluronic acid and nanoemulsions from the commercial eyedrop formulation NEOVIS® TOTAL multi, inside the lacrimal layer. [ABSTRACT FROM AUTHOR]

High pathogenicity avian influenza viruses (HPAIVs) have caused major epizootics in recent years, with devastating consequences for poultry and wildlife worldwide. Domestic and wild ducks can be highly susceptible to HPAIVs, and infection leads to efficient viral replication and massive shedding (i.e., high titres for an extended time), contributing to widespread viral dissemination. Importantly, ducks are known to shed high amounts of virus in the earliest phase of infection, but the dynamics and impact of environmental contamination on the epidemiology of HPAIV outbreaks are poorly understood. In this study, we monitored mule ducks experimentally infected with two H5N8 clade 2.3.4.4b goose/Guangdong HPAIVs sampled in France in 2016–2017 and 2020–2021 epizootics. We investigated viral shedding dynamics in the oropharynx, cloaca, conjunctiva, and feathers; bird-to-bird viral transmission; and the role of the environment in viral spread and as a source of samples for early detection and surveillance. Our findings showed that viral shedding started before the onset of clinical signs, i.e., as early as 1 day post-inoculation (dpi) or post-contact exposure, peaked at 4 dpi, and lasted for up to 14 dpi. The detection of viral RNA in aerosols, dust, and water samples mirrored viral shedding dynamics, and viral isolation from these environmental samples was successful throughout the experiment. Our results confirm that mule ducks can shed high HPAIV titres through the four excretion routes tested (oropharyngeal, cloacal, conjunctival, and feather) while being asymptomatic and that environmental sampling could be a non-invasive tool for early viral RNA detection in HPAIV-infected farms. [ABSTRACT FROM AUTHOR]

Background: Trunk inclination in patients with Acute Respiratory Distress Syndrome (ARDS) in the supine position has gained scientific interest due to its effects on respiratory physiology, including mechanics, oxygenation, ventilation distribution, and efficiency. Changing from flat supine to semi-recumbent increases driving pressure due to decreased respiratory system compliance. Positional adjustments also deteriorate ventilatory efficiency for CO2 removal, particularly in COVID-19-associated ARDS (C-ARDS), indicating likely lung parenchyma overdistension. Tilting the trunk reduces chest wall compliance and, to a lesser extent, lung compliance and transpulmonary driving pressure, with significant hemodynamic and gas exchange implications. Methods: A prospective, pilot physiological study was conducted on early ARDS patients in two ICUs at CHU Clermont-Ferrand, France. The protocol involved 30-min step gradual verticalization from a 30° semi-seated position (baseline) to different levels of inclination (0°, 30°, 60°, and 90°), before returning to the baseline position. Measurements included tidal volume, positive end-expiratory pressure (PEEP), esophageal pressures, and pulmonary artery catheter data. The primary endpoint was the variation in transpulmonary driving pressure through the verticalization procedure. Results: From May 2020 through January 2021, 30 patients were included. Transpulmonary driving pressure increased slightly from baseline (median and interquartile range [IQR], 9 [5–11] cmH2O) to the 90° position (10 [7–14] cmH2O; P < 10–2 for the overall effect of position in mixed model). End-expiratory lung volume increased with verticalization, in parallel to decreases in alveolar strain and increased arterial oxygenation. Verticalization was associated with decreased cardiac output and stroke volume, and increased norepinephrine doses and serum lactate levels, prompting interruption of the procedure in two patients. There were no other adverse events such as falls or equipment accidental removals. Conclusions: Verticalization to 90° is feasible in ARDS patients, improving EELV and oxygenation up to 30°, likely due to alveolar recruitment and blood flow redistribution. However, there is a risk of overdistension and hemodynamic instability beyond 30°, necessitating individualized bed angles based on clinical situations. Trial registration ClinicalTrials.gov registration number NCT04371016, April 24, 2020. [ABSTRACT FROM AUTHOR]

Background/Aims: Being 'with woman' is a fundamental concept of midwifery and profoundly impacts maternal and infant wellbeing and outcomes. Understanding student midwives' experiences is vital in shaping learning strategies for positive and effective student-centred learning outcomes. This scoping review's aims were to gain meaningful insight into existing literature on students' experiences of learning to be 'with woman'. Methods: The scoping review searched the CINAHL, PubMed, AusHealth, Medline and PsycInfo databases in July 2023, October 2023 and April 2024. The search included qualitative and quantitative research studies published in English between 2018 and 2024. Articles were screened for eligibility by title, abstract and full-text review by three reviewers. Results: A total of 1172 articles were screened, with nine articles included in the review from various countries. Key themes identified were 'continuity of care', 'partnership with woman', 'preceptor and practitioner impact' and 'context and contrast'. Conclusions: Limited literature exists to explore and provide an understanding of the learning experiences and outcomes of midwifery students providing woman-centred care and developing a midwifery philosophy to be 'with woman'. [ABSTRACT FROM AUTHOR]

Working memory (WM) has been consistently linked to reading. However, the mechanism(s) linking WM to reading remain unclear. WM may indirectly exert an effect onto reading through mediators such as phonemic awareness (PA) and/or rapid automatized naming (RAN). In a sample of children with reading difficulty (n = 117), separate mediation analyses tested direct and indirect (through PA and RAN) effects of WM on untimed word decoding and recognition (i.e., basic reading skills) and timed word decoding and recognition (i.e., reading fluency). WM exerted a direct effect on basic reading skills and reading fluency. For basic reading skills, there was a significant indirect effect of WM on reading through the mediation of PA (but not through RAN). By contrast, for reading fluency, there was a significant indirect effect of WM on reading through the mediation of RAN (but not through PA). Findings reinforce the importance of WM, PA, and RAN for broad reading skills, while offering a mechanistic explanation for why poor PA and/or RAN may differentially lead to reading difficulty. [ABSTRACT FROM AUTHOR]

Smartphones have become everyday objects on which the accumulation of fingerprints is significant. In addition, a large proportion of the population regularly uses a smartphone, especially younger people. The objective of this study was to evaluate smartphones as a new matrix for toxico-epidemiology. This study was conducted during two separate events (techno and trance) at an electronic music nightclub in Grenoble, France. Data on reported drug use and whether drugs were snorted directly from the surface of the smartphone were collected using an anonymous questionnaire completed voluntarily by drug users. Then, a dry swab was rubbed for 20 s on all sides of the smartphone. The extract was analyzed by liquid chromatography coupled to tandem mass spectrometry on a Xevo TQ-XS system (Waters). In total, 122 swabs from 122 drug users were collected. The three main drugs identified were MDMA (n=83), cocaine (n=59), and THC (n=51). Based on declarative data, sensitivity ranged from 73 to 97.2 % and specificity from 71.8 to 88.1 % for MDMA, cocaine, and THC. Other substances were identified such as cocaine adulterants, ketamine, amphetamine, LSD, methamphetamine, CBD, DMT, heroin, mescaline, and several NPS. Numerous medications were also identified, such as antidepressants, anxiolytics, hypnotics, and painkillers. Different use patterns were identified between the two events. This proof-of-concept study on 122 subjects shows that smartphone swab analysis could provide a useful and complementary tool for drug testing, especially for harm-reduction programs and toxico-epidemiolgy studies, with acceptable test performance, despite declarative data. [ABSTRACT FROM AUTHOR]

Blood transfusion remains an important aspect of patient management in visceral leishmaniasis (VL). However, transfusion triggers considered are poorly understood. This review summarises the transfusion practices adopted in VL efficacy studies using the Infectious Diseases Data Observatory VL clinical trials library. Of the 160 studies (1980–2021) indexed in the IDDO VL library, description of blood transfusion was presented in 16 (10.0%) (n=3459 patients) studies. Transfusion was initiated solely based on haemoglobin (Hb) measurement in nine studies, combining Hb measurement with an additional condition (epistaxis/poor health/clinical instability) in three studies and the criteria was not mentioned in four studies. The Hb threshold range for triggering transfusion was 3–8 g/dL. The number of patients receiving transfusion was explicitly reported in 10 studies (2421 patients enrolled, 217 underwent transfusion). The median proportion of patients who received transfusion in a study was 8.0% (Interquartile range: 4.7% to 47.2%; range: 0–100%; n=10 studies). Of the 217 patients requiring transfusion, 58 occurred before VL treatment initiation, 46 during the treatment/follow-up phase and the time was not mentioned in 113. This review describes the variation in clinical practice and is an important initial step in policy/guideline development, where both the patient's Hb concentration and clinical status must be considered. [ABSTRACT FROM AUTHOR]

The lack of access to dermatological care is a global health crisis, with skin diseases being the fourth leading cause of nonfatal disease burden worldwide. To address this issue, the GLODERM international mentorship program was launched by the International League of Dermatological Societies – International Foundation for Dermatology. The program pairs dermatology trainees and clinicians from low- and middle-income countries with experienced mentors in global health dermatology. The program includes monthly meetings, virtual lectures, and personalized professional development opportunities. The first cohort of mentees reported improvements in leadership skills and the ability to train healthcare providers and serve patients in underserved areas. The program aims to build a network of dermatology leaders to improve access to skin health globally. [Extracted from the article]

COVID-19 and infectious diseases have been included in strategic development goals (SDG) of United Nations (UN). The SARS-CoV-2 pandemic has unveiled complex pathophysiological mechanisms underpinning COVID-19, notably inducing a systemic acquired vascular hemopathy characterized by endothelial dysfunction and intussusceptive angiogenesis, a rapid vascular remodeling process identified as a hallmark in severe COVID-19 cases affecting pulmonary and cardiac tissues. Stem cell migration have been proposed as significant regulators of this neoangiogenic process. In a monocentric cross-sectional study, through spectral flow cytometry analysis of peripheral blood mononuclear cells, we identified a distinct stem cell subpopulation mobilized in critical COVID-19. Indeed, by an unsupervised analysis generating a UMAP representation we highlighted eleven different clusters in critical and non-critical COVID-19 patients. Only one cluster was significantly associated to critical COVID-19 compared to non-critical patients. This cluster expressed the markers: CD45dim, CD34+, CD117+, CD147+, and CD143+, and were negative for CD133. Higher level of expression of hemangioblast markers CD143 were found in critical COVID-19 patients. This population, indicative of hemangioblast-like cells, suggests a key role in COVID-19-related neoangiogenesis, potentially driving the severe vascular complications observed. Our findings underscore the need for further investigation into the contributions of adult stem cells in COVID-19 pathology, offering new insights into therapeutic targets and interventions. [ABSTRACT FROM AUTHOR]

Aims Arbuscular mycorrhizal fungi (AMF) can perform significant functions within sustainable agricultural ecosystems, including vineyards. Increased AMF diversity can be beneficial in promoting plant growth and increasing resilience to environmental changes. To effectively utilize AMF communities and their benefits in vineyard ecosystems, a better understanding of how management systems influence AMF community composition is needed. Moreover, it is unknown whether AMF communities in organically managed vineyards are distinct from those in conventionally managed vineyards. Methods and Results In this study, vineyards were surveyed across the Marlborough region, New Zealand to identify the AMF communities colonizing the roots of different rootstocks grafted with Sauvignon Blanc and Pinot Noir in both conventional and organic systems. The AMF communities were identified based on spores isolated from trap cultures established with the collected grapevine roots, and by next-generation sequencing technologies (Illumina MiSeq). The identified AMF species/genera belonged to Glomeraceae, Entrophosporaceae, and Diversisporaceae. The results revealed a significant difference in AMF community composition between rootstocks and in their interaction with management systems. Conclusions These outcomes indicated that vineyard management systems influence AMF recruitment by rootstocks and some rootstocks may therefore be more suited to organic systems due to the AMF communities they support. This could provide an increased benefit to organic systems by supporting higher biodiversity. [ABSTRACT FROM AUTHOR]

Historically, pediatric liver transplantation has achieved significant milestones, yet recent innovations have predominantly occurred in adult liver transplantation due to higher caseloads and ethical barriers in pediatric studies. Emerging methods subsumed under the term artificial intelligence offer the potential to revolutionize data analysis in pediatric liver transplantation by handling complex datasets without the need for interventional studies, making them particularly suitable for pediatric research. This review provides an overview of artificial intelligence applications in pediatric liver transplantation. Despite some promising early results, artificial intelligence is still in its infancy in the field of pediatric liver transplantation, and its clinical implementation faces several challenges. These include the need for high-quality, large-scale data and ensuring the interpretability and transparency of machine and deep learning models. Ethical considerations, such as data privacy and the potential for bias, must also be addressed. Future directions for artificial intelligence in pediatric liver transplantation include improving donor-recipient matching, managing long-term complications, and integrating diverse data sources to enhance predictive accuracy. Moreover, multicenter collaborations and prospective studies are essential for validating artificial intelligence models and ensuring their generalizability. If successfully integrated, artificial intelligence could lead to substantial improvements in patient outcomes, bringing pediatric liver transplantation again to the forefront of innovation in the transplantation community. [ABSTRACT FROM AUTHOR]

This qualitative study explores the perceptions of impact associated with engaging in a therapeutic recreation-based bereavement camp for families whose child has died from serious illness. Interviews were completed with 12 parents who had participated in a three-camp cycle of the program over 12-month period, including a subgroup who had also attended a reunion camp. Interviews were also conducted with program staff. Thematic analysis generated key themes relating to the perceived impact which suggest that those engaged in this program perceived positive contributions associated with participation, including perceptions of positive impact on coping with bereavement, access to support and implications for family functioning. This study highlights the areas of impact associated with engagement in a therapeutic recreation-based bereavement intervention, and the potential contribution of wider access to these programs for families whose child has died from serious illness. [ABSTRACT FROM AUTHOR]

Introduction: Damage to the corneal nerves can result in discomfort and chronic pain, profoundly impacting the quality of life of patients. Development of novel in vitro method is crucial to better understand corneal nerve regeneration and to find new treatments for the patients. Existing in vitro models often overlook the physiology of primary sensory neurons, for which the soma is separated from the nerve endings. Methods: To overcome this limitation, our novel model combines a compartmentalized microfluidic culture of trigeminal ganglion neurons from adult mice with live-imaging and automated 3D image analysis offering robust way to assess axonal regrowth after axotomy. Results: Physical axotomy performed by a two-second aspiration led to a reproducible 70% axonal loss and altered the phenotype of the neurons, increasing the number of substance P-positive neurons 72h post-axotomy. To validate our new model, we investigated axonal regeneration after exposure to pharmacological compounds. We selected various targets known to enhance or inhibit axonal regrowth and analyzed their basal expression in trigeminal ganglion cells by scRNAseq. NGF/GDNF, insulin, and Dooku-1 (Piezo1 antagonist) enhanced regrowth by 81, 74 and 157%, respectively, while Yoda-1 (Piezo1 agonist) had no effect. Furthermore, SARM1-IN-2 (Sarm1 inhibitor) inhibited axonal regrowth, leading to only 6% regrowth after 72h of exposure (versus 34% regrowth without any compound). Discussion: Combining compartmentalized trigeminal neuronal culture with advanced imaging and analysis allowed a thorough evaluation of the extent of the axotomy and subsequent axonal regrowth. This innovative approach holds great promise for advancing our understanding of corneal nerve injuries and regeneration and ultimately improving the quality of life for patients suffering from sensory abnormalities, and related conditions. [ABSTRACT FROM AUTHOR]

This study aimed to define the optimal composition of three heterogeneous substrates of the anaerobic digestion process to maximize methane production. The investigated substrates were sewage sludge (SS), the organic fraction of municipal solid waste (OFMSW), and horse waste (HW). The optimal composition of these substrates was defined using the mixture design and, more specifically, the simplex–centroid mixture design. Customized methods and materials were employed to study the complex mixture design of these substrates. The findings revealed that the optimal mixture involved all three substrates with the composition 0.17 HW, 0.66 SS, and 0.17 OFMSW, which demonstrated the highest methane yield at 269 NmL·gVS−1. In addition, a mathematical model was developed to predict methane production based on a specific composition of co-substrates. The results were validated at the small pilot scale. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) has been shown to pose considerable clinical and economic burden; however, research quantifying the excess burden attributable to common psychiatric comorbidities of ADHD among pediatric patients is scarce. This study assessed the impact of anxiety and depression on healthcare resource utilization (HRU) and healthcare costs in pediatric patients with ADHD in the United States. Methods: Patients with ADHD aged 6–17 years were identified in the IQVIA PharMetrics Plus database (10/01/2015-09/30/2021). The index date was the date of initiation of a randomly selected ADHD treatment. Patients with ≥ 1 diagnosis for anxiety and/or depression during both the baseline (6 months pre-index) and study period (12 months post-index) were classified in the ADHD+anxiety/depression cohort; those without diagnoses for anxiety nor depression during both periods were classified in the ADHD-only cohort. Entropy balancing was used to create reweighted cohorts. All-cause HRU and healthcare costs during the study period were compared using regression analyses. Cost analyses were also performed in subgroups by comorbid conditions. Results: The reweighted ADHD-only cohort (N = 204,723) and ADHD+anxiety/depression cohort (N = 66,231) had similar characteristics (mean age: 11.9 years; 72.8% male; 56.2% had combined inattentive and hyperactive ADHD type). The ADHD+anxiety/depression cohort had higher HRU than the ADHD-only cohort (incidence rate ratios for inpatient admissions: 10.3; emergency room visits: 1.6; outpatient visits: 2.3; specialist visits: 5.3; and psychotherapy visits: 6.1; all p < 0.001). The higher HRU translated to greater all-cause healthcare costs; the mean per-patient-per-year (PPPY) costs in the ADHD-only cohort vs. ADHD+anxiety/depression cohort was $3,988 vs. $8,682 (p < 0.001). All-cause healthcare costs were highest when both comorbidities were present; among patients with ADHD who had only anxiety, only depression, and both anxiety and depression, the mean all-cause healthcare costs were $7,309, $9,901, and $13,785 PPPY, respectively (all p < 0.001). Conclusions: Comorbid anxiety and depression was associated with significantly increased risk of HRU and higher healthcare costs among pediatric patients with ADHD; the presence of both comorbid conditions resulted in 3.5 times higher costs relative to ADHD alone. These findings underscore the need to co-manage ADHD and psychiatric comorbidities to help mitigate the substantial burden borne by patients and the healthcare system. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate and compare the long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma and assess the prognostic factors associated with surgical outcome. Methods: A 48-month retrospective analysis was performed on n = 133 open angle glaucoma eyes treated with canaloplasty and n = 57 open angle glaucoma eyes treated with phaco-canaloplasty by a single surgeon. Surgical success was defined according to six criteria, achieving a target intraocular pressure (IOP) ≤ 21, 18 or 15 mmHg on glaucoma medications (qualified success) or without any further treatment (complete success), including laser therapy or surgery. Kaplan–Meier survival analysis and Cox regression analysis were performed to evaluate surgical success and preoperative factors associated with surgical outcome. Surgical complications in the early postoperative period were compared between canaloplasty and phaco-canaloplasty. Results: Canaloplasty and phaco-canaloplasty significantly reduced postoperative IOP and number of glaucoma medications (p = 0.001 for both). Phaco-canaloplasty showed higher rates of cumulative surgical success over canaloplasty, but only for target IOP ≤ 21 and ≤ 18 (p = 0.018 and p = 0.011, respectively). A preoperative number of > 4 glaucoma medications predicted surgical failure. Phaco-canaloplasty was associated with a higher rate of IOP peaks in the first month compared with canaloplasty (40.4% vs 12.7%, p = 0.000). Conclusion: Canaloplasty and phaco-canaloplasty demonstrated long-term efficacy in the treatment of open angle glaucoma, with phaco-canaloplasty showing higher rates of surgical success compared to canaloplasty, but not for target IOPs lower than 16 mmHg. Patients on more than 4 preoperative glaucoma medications may not be good candidates for canaloplasty and may benefit from other surgical options. [ABSTRACT FROM AUTHOR]

Cognitive behaviour therapy for psychosis (CBTp) should be offered to patients receiving psychiatric inpatient care, yet very little is known about patients' perspectives on this. The aim of this study was to examine patients' experiences of a CBTp‐informed intervention delivered in inpatient settings. We recruited 10 participants from the intervention arm of a randomised controlled trial examining the feasibility and acceptability of a CBTp‐informed intervention for psychiatric inpatient settings. We undertook semistructured interviews examining their experiences of the intervention and analysed them using thematic analysis. The study was conducted in partnership with a coproduction group of key stakeholders (people with lived experience, family and carers, and clinicians). The intervention was found helpful by almost all participants, and all participants would recommend it to others in similar situations to themselves. The results demonstrated that participants valued the therapist's professionalism and emphasised the importance of the therapeutic relationship. Participants highlighted the importance of the therapy focusing on navigating admission and developing skills to manage the crisis experience so they could return to their normal lives. Participants described challenges to having psychological therapy in the acute crisis context including therapy interruptions and ongoing distressing experiences of psychosis. The study demonstrated the importance of prioritising the therapeutic relationship, that therapy was a valued process to navigate admission and discharge, but that some environmental and patient‐level challenges were present. Further research is needed to explore inpatients' experiences of psychological interventions in this setting. Trial Registration: ISRCTN trial registry: ISRCTN59055607 [ABSTRACT FROM AUTHOR]

Purpose: Severe acute respiratory distress syndrome (ARDS) with PaO2/FiO2 < 80 mmHg is a life-threatening condition. The optimal management strategy is unclear. The aim of this meta-analysis was to compare the effects of low tidal volumes (Vt), moderate Vt, prone ventilation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on mortality in severe ARDS. Methods: We performed a frequentist network meta-analysis of randomised controlled trials (RCTs) with participants who had severe ARDS and met eligibility criteria for VV-ECMO or had PaO2/FiO2 < 80 mmHg. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to discern the relative effect of interventions on mortality and the certainty of the evidence. Results: Ten RCTs including 812 participants with severe ARDS were eligible. VV-ECMO reduces mortality compared to low Vt (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.59–0.99, moderate certainty) and compared to moderate Vt (RR 0.75, 95% CI 0.57–0.98, low certainty). Prone ventilation reduces mortality compared to moderate Vt (RR 0.78, 95% CI 0.66–0.93, high certainty) and compared to low Vt (RR 0.81, 95% CI 0.63–1.02, moderate certainty). We found no difference in the network comparison of VV-ECMO compared to prone ventilation (RR 0.95, 95% CI 0.72–1.26), but inferences were based solely on indirect comparisons with very low certainty due to very wide confidence intervals. Conclusions: In adults with ARDS and severe hypoxia, both VV-ECMO (low to moderate certainty evidence) and prone ventilation (moderate to high certainty evidence) improve mortality relative to low and moderate Vt strategies. The impact of VV-ECMO versus prone ventilation remains uncertain. [ABSTRACT FROM AUTHOR]

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Background: The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event‐free survival and provide a rationale for risk stratification in future trials. Methods: The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005‐000217‐35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second‐order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5‐year event‐free survival (EFS) probabilities. Results: The EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%–73.1%) and 81.0% (95% confidence interval, 78.9%–82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5‐year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low‐risk, intermediate‐risk, high‐risk, and very‐high‐risk groups, respectively, and the corresponding 5‐year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively. Conclusions: The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG. Traditional clinical factors, together with FOXO1 fusion status, in nonmetastatic rhabdomyosarcoma were investigated to develop a predictive model for event‐free survival and provide a rationale for risk stratification in future trials. The most important result was the replacement of histology with fusion status, and this model was used for patient stratification in the new European Pediatric Soft Tissue Sarcoma Study Group Frontline and Relapse Rhabdomyosarcoma trial (ClinicalTrials.gov identifier NCT04625907). [ABSTRACT FROM AUTHOR]

Aims Patients with heart failure (HF) experience various signs and symptoms and have difficulties in perceiving them. Integrating insights from patients who have engaged in the process of symptom perception is crucial for enhancing our understanding of the theoretical concept of symptom perception. This study aimed to describe how patients with HF perceive symptoms through the processes of monitoring, awareness, and evaluation and what influences the process. Methods and results Using a qualitative descriptive design, we conducted in-person semi-structured interviews with a purposeful sample of 40 adults experiencing an unplanned hospitalization for a HF symptom exacerbation. We elicited how patients monitor, become aware of, and evaluate symptoms prior to hospitalization. Data were analysed using directed qualitative content analysis. One overarching theme and three major themes emerged. Patients demonstrated Body listening , which involved active and individualized symptom monitoring tactics to observe bodily changes outside one's usual range. Trajectory of bodily change involved the patterns or characteristics of bodily changes that became apparent to patients. Three subthemes— sudden and alarming change , gradual change , and fluctuating change emerged. Patients evaluated symptoms through an Exclusionary process , sequentially attributing symptoms to a cause through a cognitive process of excluding possible causes until the most plausible cause remained. Facilitators and barriers to symptom monitoring, awareness, and evaluation were identified. Conclusion This study elaborates the comprehensive symptom perception process used by adults with HF. Tailored nursing interventions should be developed based on the factors identified in each phase of the process to improve symptom perception in HF. [ABSTRACT FROM AUTHOR]