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Abstract Purpose We investigated the safety of primary hip and knee replacements with same day discharge (SDD) and their effect on length of stay (LOS) of traditional inpatient arthroplasties at our elective orthopaedic ward. Methods 200 patients underwent elective, unilateral primary day case total hip (THA, n = 94), total knee (TKA, n = 60) and unicondylar knee replacements (UKA, n = 46). SDD rates, reasons for failure to discharge, readmission, complication and satisfaction rates were recorded at 6-week follow up. Changes in LOS of inpatient arthroplasties (n = 6518) and rate of patients discharged with only one night stay treated at the same ward were tracked from 1 year prior to introduction of day case arthroplasty (DCA) program to the end of observation period. Results 166 patients (83%) had SDD while 34 (17%) needed overnight stay. Main reasons for failure to discharge were lack of confidence (4%) fainting due to single vasovagal episode (3.5%), urine retention (3%) and late resolution of spinal anaesthesia (3%). 5 patients (3%) had readmission within 6 weeks, including 1 (0.6%) with a partial and treated pulmonary embolism. 163 patients were satisfied with SDD (98%). After launching the DCA program, average LOS of inpatients was reduced from 2.3 days to 1.8 days and rate of discharge with only 1-night stay increased from 12% to around 60%. Conclusion Introduction of routine SDD hip and knee arthroplasty programme at an elective orthopaedic centre is safe and also may confer wider benefits leading to shorter inpatient hospital stays.

Abstract Background Tissue fibrosis is a common pathway to failure in many organ systems and is the cellular and molecular driver of myriad chronic diseases that are incompletely understood and lack effective treatment. Recent studies suggest that gut microbe-dependent metabolites might be involved in the initiation and progression of fibrosis in multiple organ systems. Main body of the manuscript In a meta-organismal pathway that begins in the gut, gut microbiota convert dietary precursors such as choline, phosphatidylcholine, and L-carnitine into trimethylamine (TMA), which is absorbed and subsequently converted to trimethylamine N-oxide (TMAO) via the host enzyme flavin-containing monooxygenase 3 (FMO3) in the liver. Chronic exposure to elevated TMAO appears to be associated with vascular injury and enhanced fibrosis propensity in diverse conditions, including chronic kidney disease, heart failure, metabolic dysfunction-associated steatotic liver disease, and systemic sclerosis. Conclusion Despite the high prevalence of fibrosis, little is known to date about the role of gut dysbiosis and of microbe-dependent metabolites in its pathogenesis. This review summarizes recent important advances in the understanding of the complex metabolism and functional role of TMAO in pathologic fibrosis and highlights unanswered questions.

Abstract Background The effective management of surgical and anesthesia care relies on quality data and its readily availability for both patient-centered decision-making and facility-level improvement efforts. Recognizing this critical need, the Strengthening Systems for Improved Surgical Outcomes (SSISO) project addressed surgical care data management and information use practices across 23 health facilities from October 2019 to September 2022. This study aimed to evaluate the effectiveness of SSISO interventions in enhancing practices related to surgical data capture, reporting, analysis, and visualization. Methods This study employed a mixed method, pre- post intervention evaluation design to assess changes in data management and utilization practices at intervention facilities. The intervention packages included capacity building trainings, monthly mentorship visits facilitated by a hub-and-spoke approach, provision of data capture tools, and reinforcement of performance review teams. Data collection occurred at baseline (February – April 2020) and endline (April – June 2022). The evaluation focused on the availability and appropriate use of data capture tools, as well as changes in performance review practices. Appropriate use of registers was defined as filling all the necessary data onto the registers, and this was verified by completeness of selected key data elements in the registers. Results The proportion of health facilities with Operation Room (OR) scheduling, referral, and surgical site infection registers significantly increased by 34.8%, 56.5% and 87%, respectively, at project endline compared to baseline. Availability of OR and Anesthesia registers remained high throughout the project, at 91.3% and 95.6%, respectively. Furthermore, the appropriate use of these registers improved, with statistically significant increases observed for OR scheduling registers (34.8% increase). Increases were also noted for OR register (9.5% increase) and anesthesia register (4.5% increase), although not statistically significant. Assessing the prior three months reports, the report submissions to the Ministry of Health/Regional Health Bureau (MOH/RHB) rose from 85 to 100%, reflecting complete reporting at endline period. Additionally, the proportion of surgical teams analyzing and displaying data for informed decision-making significantly increased from 30.4% at baseline to 60.8% at endline period. Conclusion The implemented interventions positively impacted surgical data management and utilization practice at intervention facilities. These positive changes were likely attributable to capacity building trainings and regular mentorship visits via hub-and-spoke approach. Hence, we recommend further investigation into the effectiveness of similar intervention packages in improving surgical data management, data analysis and visualization practices in low- and middle-income country settings.

Abstract Objectives Neutrophils and neutrophil extracellular traps (NETs) contribute to the vascular complications of multiple diseases, but their role in systemic sclerosis (SSc) is understudied. We sought to test the hypothesis that NETs are implicated in SSc vasculopathy and that treatment with prostacyclin analogs may ameliorate SSc vasculopathy not only through vasodilation but also by inhibiting NET release. Methods Blood from 125 patients with SSc (87 diffuse cutaneous SSc and 38 limited cutaneous SSc) was collected at a single academic medical center. Vascular complications such as digital ulcers, pulmonary artery hypertension, and scleroderma renal crisis were recorded. The association between circulating NETs and vascular complications was determined using in vitro and ex vivo assays. The impact of the synthetic prostacyclin analog epoprostenol on NET release was determined. Results Neutrophil activation and NET release were elevated in patients with SSc-associated vascular complications compared to matched patients without vascular complications. Neutrophil activation and NETs positively correlated with soluble E-selectin and VCAM-1, circulating markers of vascular injury. Treatment of patients with digital ischemia with a synthetic prostacyclin analog boosted neutrophil cyclic AMP, which was associated with the blunting of NET release and reduced NETs in circulation. Conclusion Our study demonstrates an association between NETs and vascular complications in SSc. We also identified the potential for an additional therapeutic benefit of synthetic prostacyclin analogs, namely to reduce neutrophil hyperactivity and NET release in SSc patients.

The urban land-use allocation problem is a spatial optimization problem that allocates optimum land-uses to specific land units in urban areas. This problem is an NP (nondeterministic polynomial time)-hard problem because of involving many objective functions, many constraints, and complex search space. Moreover, this subject is an important issue in smart cities and newly developed areas of cities to achieve a sustainable arrangement of land-uses. Different types ofMulti-Objective Optimization Algorithms (MOOAs) based on Artificial Intelligence (AI) have been frequently employed, but their ability and performance have not been evaluated and compared properly. This paper aims to employ and compare three commonly used MOOAs i.e. NSGA-II, MOPSO, and MOEA/D in urban land-use allocation problems. Selected algorithms belong to different categories of MOOAs family to investigate their advantage and disadvantages. The objective functions of this study are compatibility, dependency, suitability, and compactness of land-uses and the constraint is compensating of Per-Capita demand in the urban environment. Evaluation of results is based on the dispersion of the solutions, diversity of the solutions’ space, and comparing the number of dominant solutions in Pareto-Fronts. The results showed that all three algorithms improved the objective functions related to the current arrangement of the land-uses. However, the run time of NSGA-II is the worst, related to the Diversity Metric (DM) which represents the regularity of the distance between solutions at the highest degree. Moreover, MOPSO provides the best Scattering Diversity Metric (SDM) which shows the diversity of solutions in the solution space. Furthermore, In terms of algorithm execution time, MOEA/D performed better than the other two. So, Decision-makers should consider different aspects in choosing the appropriate MOOA for land-use management problems.

Abstract Filaments made of residues 120-254 of transmembrane protein 106B (TMEM106B) form in an age-dependent manner and can be extracted from the brains of neurologically normal individuals and those of subjects with a variety of neurodegenerative diseases. TMEM106B filament formation requires cleavage at residue 120 of the 274 amino acid protein; at present, it is not known if residues 255-274 form the fuzzy coat of TMEM106B filaments. Here we show that a second cleavage appears likely, based on staining with an antibody raised against residues 263-274 of TMEM106B. We also show that besides the brain TMEM106B inclusions form in dorsal root ganglia and spinal cord, where they were mostly found in non-neuronal cells. We confirm that in the brain, inclusions were most abundant in astrocytes. No inclusions were detected in heart, liver, spleen or hilar lymph nodes. Based on their staining with luminescent conjugated oligothiophenes, we confirm that TMEM106B inclusions are amyloids. By in situ immunoelectron microscopy, TMEM106B assemblies were often found in structures resembling endosomes and lysosomes.

Abstract Introduction Systemic sclerosis (SSc) is a rare, complex autoimmune rheumatic disease with multiple factors that contribute to pain. People with SSc emphasize the effect pain has on their quality of life, but no studies have systematically examined the frequency and relative importance of different SSc pain sources, patterns of pain from different sources, and pain management experiences. Our objectives are to (1) develop a tool, jointly with researchers, health care providers, and patients, to map sources of pain in SSc, determine patterns of pain from different sources, and understand pain management experiences; and (2) administer the final tool version to participants in the large multinational Scleroderma Patient-centered Intervention Network (SPIN) Cohort. Methods First, we will use validated pain assessment tools as templates to develop an initial version of our pain assessment tool, and we will obtain input from patient advisors to adapt it for SSc. The tool will include questions on pain sources, pain patterns, pain intensity, pain management techniques, and barriers to pain management in SSc. Second, we will conduct nominal group technique sessions with people living with SSc and health care providers who care for people with SSc to further refine the tool. Third, we will conduct individual usability testing sessions with SPIN Cohort participants. Once the tool has been finalized, we will administer it to individuals in the multinational SPIN Cohort, which currently includes over 1,300 active participants from 54 sites in 7 countries. We will perform unsupervised clustering using the KAy-Means for MIxed LArge data (KAMILA) method to identify participant subgroups with similar profiles of pain sources (present or absent) and to evaluate predictors of subgroup membership. We will use latent profile analysis to identify subgroups of participants with similar profiles based on pain intensity scores for each pain source and evaluate predictors. Discussion Once completed, our pain assessment tool will allow our team and other researchers to map sources of pain in SSc and to understand pain management experiences of people living with SSc. This knowledge will provide avenues for studies on the pathophysiology of pain in SSc and studies of interventions to improve pain management.

The relationship between a performer’s conscious involvement or investment in movement control and monitoring and the ability to inhibit the movement is still unclear. We conducted three experiments to investigate whether a higher inclination for conscious movement investment benefits the inhibition of a simple keypress response. In all experiments, the inclination for conscious movement investment was measured with the Movement-Specific Reinvestment Scale. In Experiment 1, participants performed the go/no-go task and conscious investment was manipulated by directing conscious attention either to the finger movement (i.e., internal focus) or to the resulting motion of the key (i.e., external focus). The results showed that neither the participants’ inclination for conscious movement investment, nor the direction of conscious attention affected inhibition performance. In Experiment 2, participants performed the stop-signal task, which is more attention demanding than the go/no-go task. The results showed that participants with a high or low inclination for conscious movement investment did not differ in inhibition performance. In Experiment 3 an ego-depletion procedure was included that limits resources for conscious movement investment. Before and after this ego-depletion procedure, participants performed the stop-signal task. The results showed that participants with a high inclination for conscious movement investment slowed down inhibition when they felt mentally depleted, while no slowing down of inhibition was found among participants who felt less depleted and/or had a low inclination for conscious movement investment. Together, the study provides evidence that increased conscious movement investment is beneficial for movement inhibition. Yet, these effects only emerge against the dynamic background of interacting individual (e.g., inclination for conscious movement investment, available attentional resources) and task constraints (e.g., task difficulty).

Abstract Addressing ecological impacts with effective conservation actions requires information on the links between human pressures and localized responses. Understanding links is a priority for many conservation contexts, including the world's fresh waters, which face intensifying threats to disproportionately high species diversity, including more than half of the world's fish species. Literature synthesis can uncover links and highlight potential research gaps, yet can be very cumbersome and time consuming. Emerging tools like text mining can improve efficiency in extracting relevant information from vast scientific outputs. This study synthesizes evidence of direct anthropogenic threats to major inland fisheries and examines driver‐impact‐response patterns using coupled automated and manual text classification methods. We screened 9336 abstracts from 45 river basins of high importance to inland fish production; 1152 abstracts contained evidence of direct threats to fish. The most common documented drivers were pollution, dams, and fishing pressure, which were most strongly linked to decreased fitness, altered reproduction, and mortality, respectively. Strong impact‐response links to pollution signal potential bias toward documenting acute threats that generate more visible and immediate impacts. The use of machine learning‐based text classification performed best in classifying extraneous information. Results can inform the development of inland fisheries indicators and threat‐based metrics, highlight possible evidence gaps in linking global drivers to fishery‐level responses, and illustrate the application of a coupled synthesis approach for improved efficiency and extraction of information relevant to conservation outcomes. The associated user and interpretation guides address accessibility and technical barriers faced by conservation scientists to improve efficiency in evidence synthesis.

Abstract Objective To evaluate the pharmacokinetics (PK), safety, and tolerability of brivaracetam (BRV) in neonates with repeated electroencephalographic seizures not controlled with previous antiseizure medications (ASMs). Methods Phase 2/3, multicenter, open‐label, single‐arm study (N01349/NCT03325439) in neonates with repeated electroencephalographic seizures (lasting ≥10 s) confirmed by video‐electroencephalography, and inadequate seizure control with at least one ASM. A screening period (up to 36 h) was followed by a 48‐h evaluation period during which patients received 0.5 mg/kg BRV twice daily (b.i.d) intravenously (IV). Patients who benefitted from BRV (investigator's opinion) could continue 0.5 mg/kg b.i.d (IV or oral solution) in an extension period. Outcomes included plasma concentrations of BRV following the first dose (primary), and incidence of treatment‐emergent adverse events (TEAEs). Results Six patients (median [range] postnatal age: 1.5 [1.0, 6.0] days) received ≥1 dose of BRV. All six patients completed the evaluation period; two entered and completed the extension period. Overall (evaluation and extension periods), three patients received one dose of 0.5 mg/kg BRV and three received more than one dose. The median (range) duration of exposure to BRV (IV and oral solution) was 1.5 (1.0, 29.0) days (n = 6). At 0.5–1, 2–4, and 8–12 h following IV BRV administration, the GeoMean (GeoCV) plasma concentrations of BRV were 0.53 mg/L (15.40% [n = 5]), 0.50 mg/L (28.20% [n = 6]), and 0.34 mg/L (13.20% [n = 5]), respectively. Individual and population BRV PK profiles were estimated, and individual PK parameters were calculated using Bayesian feedback. The observed concentrations were consistent with the predicted PK. Three patients experienced four TEAEs, none of which were considered related to BRV. Significance BRV plasma concentrations in neonates were consistent with data in older children receiving BRV oral solution, and with data from adults receiving a nominal IV dose of 25 mg b.i.d. BRV was well tolerated, with no drug‐related TEAEs reported. Plain Language Summary Few drugs are available to treat seizures in newborn babies. Brivaracetam is approved to treat focal‐onset seizures in children and adults in Europe (patients 2 years of age and older) and the United States (patients 1 month of age or older). In this study, six newborns with repeated seizures were treated with intravenous brivaracetam. The study doctors took samples of blood from the newborns and measured the levels of brivaracetam. The concentrations of brivaracetam in the newborns’ blood plasma were consistent with data from studies in older children and in adults. No brivaracetam‐related medical problems were reported.

A cyclic economy and sustainability-driven production are key aspects of the industry. Recycled feedstocks are steadily replacing virgin materials to produce parts and as sustainable additives to develop eco-friendly composites. The reinforcing potential of recycled fine powder glass (FPG) on terephthalate glycol (PETG) is investigated. The performances of six different compounds (with FPG loadings of 2.0, 4.0, 6.0, 8.0, 10.0, and 12.0 wt%) in filament and three-dimensional (3D) specimens form (manufactured with the material extrusion – MEX method) were compared with PETG pure. This research included thermal and rheological analyses, mechanical tests, and morphological and structural investigations. According to these findings, the PETG/RFPG 8.0 wt% composite presented remarkable results in the tensile and flexural (16.3 % and 16.9 % strength increase, respectively) tests, while PETG/RFPG 10.0 wt% had the greatest performance concerning microhardness. Both the dimensional deviation and porosity results show excellent performance in the case of PETG/RFPG 6.0 wt%, by being 67.3 % and 87.1 % improved vs. the PETG pure. These results indicate that RFPG is a promising reinforcement additive for MEX 3D printing that can replace the commonly used inorganic fillers and promote the sustainability of 3D printing.

ObjectivePiperacillin/tazobactam (PIP/TAZ) is used for the treatment of lower respiratory tract bacterial infections in children. This study was performed to evaluate if the current dosing regimen results in therapeutic drug concentrations.Patients and methodsPatients suspected or proven to have lower respiratory tract bacterial infection and administrated PIP/TAZ intravenously for a duration of no less than 0.5 h, q6h–q12h daily, were enrolled. Blood samples were collected, and PIP concentrations were determined by high-performance liquid chromatography. The individual predicted concentration of PIP was evaluated using the individual empirical Bayesian estimate method. The evaluated PK/PD targets included (1) 70% time when the predicted free drug concentration exceeds the minimum inhibitory concentration (fT > MIC) and (2) 50% fT > 4× MIC. Probability of target attainment (PTA) was assessed by the proportion of patients who reached the PK/PD targets. The PIP concentrations between different groups of patients were compared.ResultsA total of 57 samples were collected from 57 patients with a median age of 2.26 years (0.17–12.58). For the PK/PD targets of 70% fT > MIC and 50% fT > 4× MIC for Pseudomonas aeruginosa and Klebsiella pneumoniae, the PTA was all 0. The median Cmin of PIP was significantly higher in infants than in children, and the median Cmin after administration in q8h was significantly higher than that after administration in q12h.ConclusionThe current dose regimen of PIP/TAZ leads to extremely low plasma concentrations in most children with lower respiratory tract bacterial infections. More optimized dosing regimens or better alternative therapies need to be further explored.

Summary: Background: Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections. Methods: Five β-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses. Findings: For a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT > MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was >80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses. Interpretation: An ML-based CDSS was successfully constructed to assist clinicians in selecting optimal β-lactam antibiotic doses. Funding: This work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.

Los gliomas múltiples (multifocales y multicéntricos) son poco frecuentes en los gliomas de bajo grado. La etiología de los gliomas multicéntricos es poco conocida y su manejo es controversial. Se presenta el caso de una paciente de 27 años, con dos lesiones compatibles imagenológicamente con glioma de bajo grado, confirmado por estudio anatomopatológico; recibe manejo con quimioterapia y radioterapia manteniéndose la enfermedad estable a un año de seguimiento; no pudo ser sometida a cirugía debido a que las lesiones se encontraban en áreas elocuentes. Para este tipo de pacientes el tratamiento de elección es la cirugía, siempre que sea factible, según elocuencia y compromiso vascular, seguido de esquemas de quimioterapia y radioterapia, según el esquema que se da en gliomas únicos. Por ello, los gliomas multicéntricos de bajo grado son una patología rara que debe ser manejado por un equipo multidisciplinario donde la cirugía es el tratamiento de elección, siempre que sea factible, seguido de quimioterapia y radioterapia.

Background:. Exposure to ultraviolet radiation is a leading risk factor for developing all types of skin cancer. In the United States, an estimated 7.8 million young adults engage in indoor tanning. Objective:. Here, it is hypothesized that certain populations of students at undergraduate universities, namely sorority members, have a greater frequency of tanning bed usage than other groups of students and that regardless of sorority status, the most important motivating factor will be the intent to enhance one’s appearance. Methods:. Undergraduate students at 2 state-funded universities were recruited for participation in this institutional review board-exempt survey via distribution to e-mail addresses and social media accounts affiliated with student organizations/clubs. Results:. Among all respondents, the most common motivating factors for tanning bed use were the perception of improved self-appearance and boosted self-confidence. Female sorority members were more likely to use tanning beds and also more likely to report being motivated by enhanced appearance and self-confidence, than their female counterparts who were not sorority members. Limitations:. The sample size (n = 321) and population of this study allows data to only be generalizable to surrounding states with similar demographics. The findings of this study are subject to recall bias as the data is self-reported. Conclusion:. Tanning bed use remains a popular practice among young people. Understanding motivations for tanning bed use among populations at increased risk of partaking in this behavior allows for educating these groups on the risks associated with ultraviolet radiation exposure. It is crucial that providers continue to promote skin health and take steps to dissuade detrimental practices and possible habit-forming behaviors at the individual and state levels.

Introduction: Chronic subdural hematomas (CSDH) are common problems in neurosurgery, generally secondary to head trauma, although they me be in rare cases associated to underlying pathologies. Between these possible causes, arachnoid cysts (usually asymptomatic benign congenital lesions) can be a risk factor for subdural hematoma in young patients, who may spontaneously develop a CSDH and require surgery to relieve intracranial hypertension.Case Report.We present the case of a 23-year-old male, incidentally diagnosed two years before with a right temporal arachnoid cyst (middle fossa), asymptomatic, who began with symptoms of intracranial hypertension two weeks prior to surgery. A right fronto-parieto-temporal CSDH was verified on MRI, requiring emergency surgery with a small craniotomy, evacuation of the hematoma, and fenestration of the arachnoid cyst. Conclusions: In young patients with a diagnosis of an arachnoid cyst, the differential diagnosis of CSDH should be considered when presenting with acute neurological symptoms.

Objective: Neurocysticercosis (NCC) is still a frequent cause of neurosurgical consultations in most developing countries. Conventional approaches for the resection of large cysts have been used for many years. We report here our experience in the neurosurgical management of NCC using diverse minimally invasive approaches according to the localization of lesions: minimal craniotomy for lesions in the Sylvian fissure, stereotactic surgery for lesions in the posterior fossa, and endonasal neuroendoscopy for lesions in the basal cisterns. Methods: We reviewed the charts of 24 consecutive NCC patients who had minimally invasive surgery to resect NCC lesions in a neurological referral center in Lima, Peru. Three approaches were used: microcraneotomies through the anterior Sylvian point (n = 16), stereotactic surgery (n = 6), and endonasal endoscopy (n = 2), between January 1, 2016, and July 31, 2022. Demographic and clinical data as well as post-surgical evolution are presented using descriptive statistics. Results: Clinical improvement was observed in 23 out of 24 cases, with complete resolution of symptoms in nine and partial in 14. One patient evolved poorly and worsened his symptoms. Twenty-two patients received antiparasitic treatment after surgery. Relapse of NCC lesions was observed in three patients. There were no significant complications in any of the cases. Conclusions: Minimally invasive surgical approaches provide an excellent alternative for the management of patients with NCC, with good surgical and functional results, also markedly reducing the parasitic mass for further antiparasitic treatment.

Objective There are no globally agreed on strategies on early detection and first response management of postpartum haemorrhage (PPH) during and after caesarean birth. Our study aimed to develop an international expert’s consensus on evidence-based approaches for early detection and obstetric first response management of PPH intraoperatively and postoperatively in caesarean birth.Design Systematic review and three-stage modified Delphi expert consensus.Setting International.Population Panel of 22 global experts in PPH with diverse backgrounds, and gender, professional and geographic balance.Outcome measures Agreement or disagreement on strategies for early detection and first response management of PPH at caesarean birth.Results Experts agreed that the same PPH definition should apply to both vaginal and caesarean birth. For the intraoperative phase, the experts agreed that early detection should be accomplished via quantitative blood loss measurement, complemented by monitoring the woman’s haemodynamic status; and that first response should be triggered once the woman loses at least 500 mL of blood with continued bleeding or when she exhibits clinical signs of haemodynamic instability, whichever occurs first. For the first response, experts agreed on immediate administration of uterotonics and tranexamic acid, examination to determine aetiology and rapid initiation of cause-specific responses. In the postoperative phase, the experts agreed that caesarean birth-related PPH should be detected primarily via frequently monitoring the woman’s haemodynamic status and clinical signs and symptoms of internal bleeding, supplemented by cumulative blood loss assessment performed quantitatively or by visual estimation. Postoperative first response was determined to require an individualised approach.Conclusion These agreed on proposed approaches could help improve the detection of PPH in the intraoperative and postoperative phases of caesarean birth and the first response management of intraoperative PPH. Determining how best to implement these strategies is a critical next step.

Abstract Systemic sclerosis (SSc) is a devastating autoimmune disease characterized by excessive production and accumulation of extracellular matrix, leading to fibrosis of skin and other internal organs. However, the main cellular participants in SSc skin fibrosis remain incompletely understood. Here using differentiation trajectories at a single cell level, we demonstrate a dual source of extracellular matrix deposition in SSc skin from both myofibroblasts and endothelial-to-mesenchymal-transitioning cells (EndoMT). We further define a central role of Hippo pathway effectors in differentiation and homeostasis of myofibroblast and EndoMT, respectively, and show that myofibroblasts and EndoMTs function as central communication hubs that drive key pro-fibrotic signaling pathways in SSc. Together, our data help characterize myofibroblast differentiation and EndoMT phenotypes in SSc skin, and hint that modulation of the Hippo pathway may contribute in reversing the pro-fibrotic phenotypes in myofibroblasts and EndoMTs.

Singularly perturbed systems are a class of mathematical systems that are not well approximated by their limits and can be used to model plants with multiple fast and slow states. Multiple-timescale systems are very common in engineering applications, but adaptive control can be sensitive to timescale effects. Recently a method called [K]control of Adaptive Multiple-timescale Systems (KAMS) has shown improved performance and increased robustness for singularly perturbed systems, but it has only been studied on systems using adaptive control for the slow states. This article extends KAMS to the general case when adaptive control is used to stabilize both the slow and fast states simultaneously. This causes complex interactions between the fast state reference model and the manifold to which the fast states converge. It is proven that under certain conditions the system still converges to the reference model despite these complex interactions. This method is demonstrated on a nonlinear, nonstandard, numerical example.

Abstract The functionally pleiotropic ectoenzyme CD38 is a glycohydrolase widely expressed on immune and non-hematopoietic cells. By converting NAD+ to ADP-ribose and nicotinamide, CD38 governs organismal NAD+ homeostasis and the activity of NAD+-dependent cellular enzymes. CD38 has emerged as a major driver of age-related NAD+ decline underlying adverse metabolic states, frailty and reduced health span. CD38 is upregulated in systemic sclerosis (SSc), a chronic disease characterized by fibrosis in multiple organs. We sought to test the hypothesis that inhibition of the CD38 ecto-enzymatic activity using a heavy-chain monoclonal antibody Ab68 will, via augmenting organismal NAD+, prevent fibrosis in a mouse model of SSc characterized by NAD+ depletion. Here we show that treatment of mice with a non-cytotoxic heavy-chain antibody that selectively inhibits CD38 ectoenzyme resulted in NAD+ boosting that was associated with significant protection from fibrosis in multiple organs. These findings suggest that targeted inhibition of CD38 ecto-enzymatic activity could be a potential pharmacological approach for SSc fibrosis treatment.

The antiparasitic drug ivermectin is approved for persons > 15 kg in the US and EU. A pharmacometric (PMX) population model with clinical PK data was developed (i) to characterize the effect of the patient-friendly ivermectin formulation CHILD-IVITAB on the absorption process and (ii) to evaluate dosing for studies in children < 15 kg. Simulations were performed to identify dosing with CHILD-IVITAB associated with similar exposure coverage in children ≥ 15 kg and < 15 kg as observed in adults receiving the reference formulation STROMECTOL®. A total of 448 ivermectin concentrations were available from 16 healthy adults. The absorption rate constant was 2.41 h−1 (CV 19%) for CHILD-IVITAB vs. 1.56 h−1 (CV 43%) for STROMECTOL®. Simulations indicated that 250 µg/kg of CHILD-IVITAB is associated with exposure coverage in children < 15 kg consistent with that observed in children ≥ 15 kg and adults receiving 200 µg/kg of STROMECTOL®. Performed analysis confirmed that CHILD-IVITAB is associated with faster and more controlled absorption than STROMECTOL®. Simulations indicate that 250 µg/kg of CHILD-IVITAB achieves equivalent ivermectin exposure coverage in children < 15 kg as seen in children ≥ 15 kg and adults.

Robust materials in medical applications are sought after and researched, especially for 3D printing in bone tissue engineering. Poly[ε-caprolactone] (PCL) is a commonly used polymer for scaffolding and other medical uses. Its strength is a drawback compared to other polymers. Herein, PCL was mixed with hydroxyapatite (HAp). Composites were developed at various concentrations (0.0–8.0 wt. %, 2.0 step), aiming to enhance the strength of PCL with a biocompatible additive in bioplotting. Initially, pellets were derived from the shredding of filaments extruded after mixing PCL and HAp at predetermined quantities for each composite. Specimens were then manufactured by bioplotting 3D printing. The samples were tested for their thermal and rheological properties and were also mechanically, morphologically, and chemically examined. The mechanical properties included tensile and flexural investigations, while morphological and chemical examinations were carried out employing scanning electron microscopy and energy dispersive spectroscopy, respectively. The structure of the manufactured specimens was analyzed using micro-computed tomography with regard to both their dimensional deviations and voids. PCL/HAp 6.0 wt. % was the composite that showed the most enhanced mechanical (14.6% strength improvement) and structural properties, proving the efficiency of HAp as a reinforcement filler in medical applications.

The use of prophylactic measures, including perioperative antibiotics, for the prevention of surgical site infections is a standard of care across surgical specialties. Unfortunately, the routine guidelines used for routine procedures do not always account for many of the factors encountered with urgent/emergent operations and critically ill or high-risk patients. This clinical consensus document created by the American Association for the Surgery of Trauma Critical Care Committee is one of a three-part series and reviews surgical and procedural antibiotic prophylaxis in the surgical intensive care unit. The purpose of this clinical consensus document is to provide practical recommendations, based on expert opinion, to assist intensive care providers with decision-making for surgical prophylaxis. We specifically evaluate the current state of periprocedural antibiotic management of external ventricular drains, orthopedic operations (closed and open fractures, silver dressings, local, antimicrobial adjuncts, spine surgery, subfascial drains), abdominal operations (bowel injury and open abdomen), and bedside procedures (thoracostomy tube, gastrostomy tube, tracheostomy).

BACKGROUND AND AIMS: Pharmacometric in silico approaches are frequently applied to guide decisions concerning dosage regimes during the development of new medicines. We aimed to demonstrate how such pharmacometric modelling and simulation can provide a scientific rationale for optimising drug doses in the context of the Swiss national dose standardisation project in paediatrics using amikacin as a case study. METHODS: Amikacin neonatal dosage is stratified by post-menstrual age (PMA) and post-natal age (PNA) in Switzerland and many other countries. Clinical concerns have been raised for the subpopulation of neonates with a post-menstrual age of 30–35 weeks and a post-natal age of 0–14 days (“subpopulation of clinical concern”), as potentially oto-/nephrotoxic trough concentrations (Ctrough >5 mg/l) were observed with a once-daily dose of 15 mg/kg. We applied a two-compartmental population pharmacokinetic model (amikacin clearance depending on birth weight and post-natal age) to real-world demographic data from 1563 neonates receiving anti-infectives (median birth weight 2.3 kg, median post-natal age six days) and performed pharmacometric dose-exposure simulations to identify extended dosing intervals that would ensure non-toxic Ctrough (Ctrough 80%. CONCLUSION: Pharmacometric in silico studies using high-quality real-world demographic data can provide a scientific rationale for national paediatric dose optimisation. This may increase clinical acceptance of fine-tuned standardised dosing recommendations and support their implementation, including in vulnerable subpopulations.

First paragraph: Dismantling the Capitalist Industrial Food System Should Be a Priority Food systems are crucial to the stability of our planet’s ecosystems and the future of humanity. The industrial capitalist global food system has generated multiple crises that pose a significant threat to the future of our planet. The environmen­tal, health, and social impacts of this system of agri­culture are multifaceted and well-documented. Pes­ticides poison us and destroy the world’s biodiver­sity (Ali et al., 2020; Beaumelle et al., 2023; Beketov et al., 2013; Kumar et al., 2023). Pesticides and fer­tilizer runoff pollute our water and create dead zones (Craswell, 2021, Diaz & Rosenberg, 2008). Greenhouse gas emissions from the global food system contribute up to a third of total global emis­sions (Crippa et al., 2020). Land concentration and land grabbing condemn millions to poverty (DeShutter, 2011). Food insecurity persists even as food production continues to increase (Long et al., 2020l; Müller et al., 2021). Not only is our current agri-food system environmentally and socially dam­aging, but it is also extremely cost-inefficient. Diet-related health problems, for example, overburden global public health systems and affect workers’ productivity, costing an estimated 9 trillion dollars annually (Food and Agriculture Organization [FAO], 2023). . . .

Objective The objectives were to (1) compare satisfaction with social roles and activities in a large multinational systemic sclerosis (SSc) cohort to general population normative data and (2) identify sociodemographic, lifestyle and SSc disease factors associated with satisfaction with social roles and activities.Methods Participants in the Scleroderma Patient-centered Intervention Network Cohort completed the Patient Reported Outcomes Information System Version 2 satisfaction with social roles and activities domain questionnaire. Multivariable regression was used to assess associations with sociodemographic, lifestyle and disease factors.Results Among 2385 participants, mean satisfaction with social roles and activities T-score (48.1, SD=9.9) was slightly lower than the US general population (mean=50, SD=10). Factors independently associated with satisfaction were years of education (0.54 per SD, 95% CI 0.14 to 0.93); non-White race or ethnicity (−1.13, 95% CI −2.18 to –0.08); living in Canada (−1.33, 95% CI −2.40 to –0.26 (reference USA)) or the UK (−2.49, 95% CI −3.92 to –1.06); body mass index (−1.08 per SD, 95% CI −1.47 to –0.69); gastrointestinal involvement (−3.16, 95% CI −4.27 to –2.05); digital ulcers (−1.90, 95% CI −3.05 to –0.76); moderate (−1.62, 95% CI −2.78 to –0.45) or severe (−2.26, 95% CI −3.99 to –0.52) small joint contractures; interstitial lung disease (−1.11, 95% CI −1.97 to –0.25); pulmonary arterial hypertension (−2.69, 95% CI −4.08 to –1.30); rheumatoid arthritis (−2.51, 95% CI −4.28 to –0.73); and Sjogren’s syndrome (−2.42, 95% CI −3.96 to –0.88).Conclusion Mean satisfaction with social roles and activities is slightly lower in SSc than the general population and associated with multiple sociodemographic and disease factors.

Abstract One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure.

Abstract Anti-CRISPR proteins (Acrs) block the activity of CRISPR-associated (Cas) proteins, either by inhibiting DNA interference or by preventing crRNA loading and complex formation. Although the main use of Acrs in genome engineering applications is to lower the cleavage activity of Cas proteins, they can also be instrumental for various other CRISPR-based applications. Here, we explore the genome editing potential of the thermoactive type II-C Cas9 variants from Geobacillus thermodenitrificans T12 (ThermoCas9) and Geobacillus stearothermophilus (GeoCas9) in Escherichia coli. We then demonstrate that the AcrIIC1 protein from Neisseria meningitidis robustly inhibits their DNA cleavage activity, but not their DNA binding capacity. Finally, we exploit these AcrIIC1:Cas9 complexes for gene silencing and base-editing, developing Acr base-editing tools. With these tools we pave the way for future engineering applications in mesophilic and thermophilic bacteria combining the activities of Acr and CRISPR-Cas proteins.

Abstract Route of immunization can markedly influence the quality of immune response. Here, we show that intradermal (ID) but not intramuscular (IM) modified vaccinia Ankara (MVA) vaccinations provide protection from acquisition of intravaginal tier2 simian-human immunodeficiency virus (SHIV) challenges in female macaques. Both routes of vaccination induce comparable levels of serum IgG with neutralizing and non-neutralizing activities. The protection in MVA-ID group correlates positively with serum neutralizing and antibody-dependent phagocytic activities, and envelope-specific vaginal IgA; while the limited protection in MVA-IM group correlates only with serum neutralizing activity. MVA-ID immunizations induce greater germinal center Tfh and B cell responses, reduced the ratio of Th1 to Tfh cells in blood and showed lower activation of intermediate monocytes and inflammasome compared to MVA-IM immunizations. This lower innate activation correlates negatively with induction of Tfh responses. These data demonstrate that the MVA-ID vaccinations protect against intravaginal SHIV challenges by modulating the innate and T helper responses.

The failures of culverts can result in water and soil loss in the surrounding subsurface, leading to collapses. In densely constructed urban areas, buried culverts are inaccessible and invisible, making Ground Penetrating Radar (GPR) inspection a widely adopted nondestructive and efficient method. Previous research has employed artificial intelligence to automate GPR interpretation by identifying special radargram textures, but the irregular GPR responses of degraded subsurface soils present a challenge. Therefore, this study proposes a method for preliminary diagnosing large-scale culverts based on GPR wave attributes. The method comprises three parts: (1) evaluating soil compactness by estimating the tortuosity of GPR responses at the culvert top; (2) investigating soil moisture using the attenuation rate of GPR responses; and (3) overlaying the results of the incompact and moist soils to pinpoint potential degradations. Two long-distance culverts were inspected and diagnosed using the proposed method, and three abnormal sections were identified and confirmed by excavation evaluation. The case studies indicate that the proposed method can quickly provide reference for further in-depth investigation, thereby improving GPR survey efficiency and reducing workload by narrowing the investigation scope. Consequently, this study can facilitate large-scale GPR culvert surveys and further safeguard the water system.

Background: COVID-19 has dramatically affected the delivery of health care and technical assistance. This is true in Tanzania, where maternal mortality and surgical infection rates are significantly higher than in high-income countries. This paper describes lessons learned about the optimal application of in-person and virtual mentorship in the Safe Surgery 2020 program to improve the quality of surgical services in Tanzania before and after the COVID-19 pandemic. Methods: From January 2018 through December 2020, Safe Surgery 2020 supported 40 health facilities in Tanzania's Lake Zone to improve the quality of surgical care. A blended surgical mentorship model, employing both onsite and virtual mentorship, was central to the program's capacity development approach. With COVID-19, the program pivoted to full virtual mentorship. Through continuous learning and adaptation processes, including a human-centered design workshop, surveys assessing mentors' confidence with different competencies, and focus group discussions with mentors, mentees and safe surgery program staff, the program distilled the optimal use of mentorship models. Results: Developing complex surgical skills, addressing contextual considerations, problem-solving, and building trusting relationships were best suited to in-person mentorship, whereas virtual mentorship was most effective in supporting mentees' quality improvement projects, data use, case discussions, and reinforcing clinical practices. Leading successful virtual learning required enhanced facilitation skills and active engagement of health facility leadership. Conclusions: In-person and virtual mentorship offer distinct benefits and complement each other when combined. Investing more in-person mentorship at the beginning of programs allows for the establishment of trust that is foundational to effective mentorship.

This study aimed to investigate the potential of antimony-doped tin oxide (ATO) as a reinforcing agent for polyamide 12 (PA12) in 3D printing by examining four mixtures with varying ATO concentrations (2.0 to 8.0 wt.%, with a 2.0 wt.% interval). These mixtures were used to fabricate filaments for the manufacturing of specimens through the material extrusion method. The mechanical properties of the resulting PA12/ATO composites and PA12 pure samples were evaluated through tensile, Charpy impact, flexural, and microhardness tests. Additionally, rheology, structure, morphology, thermal properties, pore size, and consistency in the dimensions of the samples were evaluated. Thermogravimetric analysis, along with differential scanning calorimetry, scanning electron microscopy, energy-dispersive and Raman spectroscopy, and micro-computed tomography, were conducted. The results were correlated and interpreted. The greatest reinforcement was achieved with the PA12/ATO 4.0 wt.% mixture, which exhibited a 19.3% increase in tensile strength and an 18.6% increase in flexural strength compared with pure PA12 (the control samples). The Charpy impact strength and microhardness were also improved by more than 10%. These findings indicate the merit of composites with ATO in additive manufacturing, particularly in the production of components with improved mechanical performance.

There has been a recent increasing interest in Zn–air batteries as an alternative to Li-ion batteries. Zn–air batteries possess some significant advantages; however, there are still problems to solve, especially related to the tuning of the properties of the air–cathode which should carry an inexpensive but efficient bifunctional oxygen reduction (ORR) and oxygen evolution (OER) reaction electrocatalyst. Biochar can be an alternative, since it is a material of low cost, it exhibits electric conductivity, and it can be used as support for transition metal ions. Although there is a significant number of publications on biochars, there is a lack of data about biochar from raw biomass rich in hemicellulose, and biochar with a small number of heteroatoms, in order to report the pristine activity of the carbon phase. In this work, activated biochar has been made by using corncobs. The biomass was first dried and minced into small pieces and pyrolyzed. Then, it was mixed with KOH and pyrolyzed for a second time. The final product was characterized by various techniques and its electroactivity as a cathode was determined. Physicochemical characterization revealed that the biochar had a hierarchical pore structure, moderate surface area of 92 m2 g−1, carbon phase with a relatively low sp2/sp3 ratio close to one, and a limited amount of N and S, but a high number of oxygen groups. The graphitization was not complete while the biochar had an ordered structure and contained significant O species. This biochar was used as an electrocatalyst for ORR and OER in Zn–air batteries where it demonstrated a satisfactory performance. More specifically, it reached an open-circuit voltage of about 1.4 V, which was stable over a period of several hours, with a short-circuit current density of 142 mA cm−2 and a maximum power density of 55 mW cm−2. Charge–discharge cycling of the battery was achieved between 1.2 and 2.1 V for a constant current of 10 mA. These data show that corncob biochar demonstrated good performance as an electrocatalyst in Zn–air batteries, despite its low specific surface and low sp2/sp3 ratio, owing to its rich oxygen sites, thus showing that electrocatalysis is a complex phenomenon and can be served by biochars of various origins.

In this study, titanium nitride (TiN) was selected as an additive to a high-density polyethylene (HDPE) matrix material, and four different nanocomposites were created with TiN loadings of 2.0–8.0 wt. % and a 2 wt. % increase step between them. The mixtures were made, followed by the fabrication of the respective filaments (through a thermomechanical extrusion process) and 3D-printed specimens (using the material extrusion (MEX) technique). The manufactured specimens were subjected to mechanical, thermal, rheological, structural, and morphological testing. Their results were compared with those obtained after conducting the same assessments on unfilled HDPE samples, which were used as the control samples. The mechanical response of the samples improved when correlated with that of the unfilled HDPE. The tensile strength improved by 24.3%, and the flexural strength improved by 26.5% (composite with 6.0 wt. % TiN content). The dimensional deviation and porosity of the samples were assessed with micro-computed tomography and indicated great results for porosity improvement, achieved with 6.0 wt. % TiN content in the composite. TiN has proven to be an effective filler for HDPE polymers, enabling the manufacture of parts with improved mechanical properties and quality.

Abstract ACT‐1014‐6470 is an orally available complement factor 5a receptor 1 antagonist and a novel treatment option in auto‐inflammatory diseases. The in vitro inhibition potential of ACT‐1014‐6470 on cytochrome P450 isozymes (CYPs) and its effect on the pharmacokinetics (PK) of the CYP2C19 and CYP3A4 substrates omeprazole and midazolam, respectively, in humans were assessed. In vitro assays were conducted with isoform‐specific substrates in human liver microsomes. In an open‐label, two‐period, fixed‐sequence cocktail study, single doses of 20 mg omeprazole and 2 mg midazolam were administered concomitantly to 20 healthy male subjects alone (treatment A) and after a single dose of 100 mg ACT‐1014‐6470 (treatment B) under fed conditions. Safety and PK assessments were performed. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of noncompartmental PK parameters of treatment B versus treatment A were calculated. In vitro, no time‐dependent inhibition was observed and the lowest inhibition constant of 4.3 μM ACT‐1014‐6470 was recorded for CYP2C19. In humans, GMRs (90% CI) of omeprazole PK were 1.9 (1.5–2.5) for maximum plasma concentration (Cmax) and 1.9 (1.5–2.3) for area under the plasma concentration‐time curve from 0 to 12 h (AUC0‐12 h). Midazolam PK showed GMRs (90% CI) of 1.1 (1.1–1.2) for Cmax and 1.5 (1.4–1.6) for AUC0‐24 h. All treatments were well‐tolerated. In line with in vitro results and regulatory risk factor calculation, the increased exposure to omeprazole and midazolam in humans after concomitant administration with a single dose of 100 mg ACT‐1014‐6470 reflected a weak inhibition of CYP2C19 and CYP3A4.

Abstract Clostridium species are re-emerging as biotechnological workhorses for industrial acetone–butanol–ethanol production. This re-emergence is largely due to advances in fermentation technologies but also due to advances in genome engineering and re-programming of the native metabolism. Several genome engineering techniques have been developed including the development of numerous CRISPR-Cas tools. Here, we expanded the CRISPR-Cas toolbox and developed a CRISPR-Cas12a genome engineering tool in Clostridium beijerinckii NCIMB 8052. By controlling the expression of FnCas12a with the xylose-inducible promoter, we achieved efficient (25–100%) single-gene knockout of five C. beijerinckii NCIMB 8052 genes (spo0A, upp, Cbei_1291, Cbei_3238, Cbei_3832). Moreover, we achieved multiplex genome engineering by simultaneously knocking out the spo0A and upp genes in a single step with an efficiency of 18%. Finally, we showed that the spacer sequence and position in the CRISPR array can affect the editing efficiency outcome.

Abstract In vitro, ACE2 translocates to the nucleus to induce SARS-CoV-2 replication. Here, using digital spatial profiling of lung tissues from SARS-CoV-2-infected golden Syrian hamsters, we show that a specific and selective peptide inhibitor of nuclear ACE2 (NACE2i) inhibits viral replication two days after SARS-CoV-2 infection. Moreover, the peptide also prevents inflammation and macrophage infiltration, and increases NK cell infiltration in bronchioles. NACE2i treatment increases the levels of the active histone mark, H3K27ac, restores host translation in infected hamster bronchiolar cells, and leads to an enrichment in methylated ACE2 in hamster bronchioles and lung macrophages, a signature associated with virus protection. In addition, ACE2 methylation is increased in myeloid cells from vaccinated patients and associated with reduced SARS-CoV-2 spike protein expression in monocytes from individuals who have recovered from infection. This protective epigenetic scarring of ACE2 is associated with a reduced latent viral reservoir in monocytes/macrophages and enhanced immune protection against SARS-CoV-2. Nuclear ACE2 may represent a therapeutic target independent of the variant and strain of viruses that use the ACE2 receptor for host cell entry.

Abstract Introduction The efficacy of abatacept is enhanced in anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF)-positive versus -negative patients with rheumatoid arthritis (RA). Four early RA abatacept trials were analyzed to understand the differential impact of abatacept among patients with SeroPositive Early and Active RA (SPEAR) compared to non-SPEAR patients. Methods Pooled patient-level data from AGREE, AMPLE, AVERT, and AVERT-2 were analyzed. Patients were classified as SPEAR if they were ACPA +, RF +, disease duration

Cryptococcus neoformans classically causes pulmonary and central nervous system (CNS) infection in immunocompromised hosts and can lead to disseminated disease. Two cases of atypical cryptococcal infection are presented—an elderly Human Immunodeficiency Virus- (HIV-) negative male with a urinary source of infection and a young HIV-positive male with bone marrow infiltration complicated by haemophagocytic lymphohistiocytosis (HLH). A literature review of systemic cryptococcal infections involving the genitourinary tract and bone marrow was performed. These cases highlight the importance of clinicians considering uncommon manifestations of cryptococcal disease.

Environmental surveillance of pathogens underlying infectious disease is critical to ensure public health. Recent efforts to track SARS-CoV-2 have utilized wastewater sampling to infer community trends in viral abundance and variant composition. Indoor dust has also been used for building-level inferences, though to date no sequencing data providing variant-scale resolution have been reported from dust samples, and strategies to monitor circulating variants in dust are needed to help inform public health decisions. In this study, we demonstrate that SARS-CoV-2 lineages can be detected and sequenced from indoor bulk dust samples. We collected 93 vacuum bags from April 2021 to March 2022 from buildings on The Ohio State University's (OSU) Columbus campus, and the dust was used to develop and apply an amplicon-based whole-genome sequencing protocol to identify the variants present and estimate their relative abundances. Three variants of concern were detected in the dust: Alpha, Delta, and Omicron. Alpha was found in our earliest sample in April 2021 with an estimated frequency of 100%. Delta was the primary variant present from October of 2021 to January 2022, with an average estimated frequency of 91% (±1.3%). Omicron became the primary variant in January 2022 and was the dominant strain in circulation through March with an estimated frequency of 87% (±3.2%). The detection of these variants on OSU's campus correlates with the circulation of these variants in the surrounding population (Delta p

Transmission line silicon rubber insulators are frequently subjected to harsh environmental conditions that can change their surface characteristics and result in a transient or permanent loss of hydrophobicity. Algae, fungi, mould, and lichen are examples of biological growth that can compromise the power system’s ability to operate safely by lowering the insulator’s flashover voltage. We evaluated and identified the major microorganisms that could be responsible for the flashovers of insulators in South Africa. Due to the difficulty of accessing insulators currently in use within the electricity network, only two insulators, from two provinces in South Africa, were used in the study. Although algae were not found on the insulators, two major filamentous fungi identified as Curvularia sp. and Aspergillus sp. were isolated. The absence of algae could be attributed to the weather pattern of the two locations where the insulators were placed during their use as part of the network. According to previous studies worldwide, the high occurrence of these fungi could be linked to the reduction of flashover voltage of the composite insulators. Although a larger survey including more insulators from all provinces in South Africa should be conducted, the current study demonstrates the need for a cleaning programme for insulators using cost-effective eco-friendly antimicrobial agents. Significance: • Degradation and loss of hydrophobicity on the overhead line composite due to biological growth were found to be an impediment to the safe operation of high-voltage insulators. Fungi were found to be the main factor causing the degradation of overhead transmission lines. • With these data, a model can be developed to predict the rate of biological growth on a given insulator, to estimate the degradation of the surface conditions with time for the utility to know when to remove them from the line. Such a model could lead to a more reliable and efficient power system and reduce the engineer’s workload.

Systemic sclerosis (SSc) is a rare and heterogeneous disease with no relevant environmental trigger or significant responsible gene. It has been and will continue to be difficult to identify large enough patients to conduct classic population-based epidemiologic exposure/non-exposure studies with adequate power to ascertain environmental and genetic risk factors for these entities. The complexity of pathogenesis and heterogeneity are likely to require personalized/precision medicine for SSc. Since several potential drugs are currently available for specific patients if not whole SSc, classification of SSc seems to form the foundation for a better therapeutic strategy. To date, SSc has been classified based on the extent/severity of the affected area as well as some disease markers, including the autoantibody profile. However, such an analysis should also lead to improvements in the design of appropriately stratified clinical trials to determine the effects and prediction of targeted therapies. An approach based on drug response preclinically conducted using patients’ own fibroblasts in vitro, can provide a precise disease marker/therapeutic selection for clinical practice. Because scleroderma dermal fibroblasts have a persistent hyper-productive phenotype occurring not only in person, but also in cell culture conditions. Thus, an accumulating approach based on disease markers ensures progression and de-escalation to re-establish a better life with a personally optimized drug environment after the onset of SSc.

Summary: Improvement of alkaline water electrolysis is a key enabler for quickly scaling up green hydrogen production. Fe is omnipresent within most industrial alkaline water electrolyzers and its effect on electrolyzer performance needs to be assessed. We conducted three-electrode and flow cell experiments with electrolyte Fe and Ni electrodes. Three-electrode cell experiments show that Fe ([Fe] = 6–357 μM; ICP-OES) promotes HER and OER by lowering both overpotentials by at least 100 mV at high current densities (T = 35°C–91°C). The overpotential of a zero-gap flow cell was decreased by 200 mV when increasing the Fe concentration ([Fe] = 13–549 μM, T = 21°C–75°C). HER benefits from the formation of Fe dendrite layers (SEM/EDX, XPS), which prevent NiHx formation and increase the overall active area. The OER benefits from the formation of mixed Ni/Fe oxyhydroxides leading to better catalytic activity and Tafel slope reduction.

Buildings and the construction industry at large are significant contributors to the catastrophic climate breakdown. The built environment is responsible for 37% of the total global carbon emission, of which about a third arises from the energy used to produce building and construction materials, usually referred to as embodied carbon. One of the key strategies to reduce the environmental impact of buildings is to significantly improve their energy efficiency, which is referred to as deep renovation. Prefabricated building envelope elements intended to prevent heat loss through the building envelope are considered a key deep-renovation technology. Connecting prefabricated elements to a building reflects a potential stream of waste if applied linearly with severe negative environmental impact in terms of natural resource depletion and exposure to pollutants. This article reports on a quantitative Design for Disassembly (Dfd) indicator to assess future recovery potential and, subsequently, its impact on embodied carbon emission of the circular redesign of three different prefabricated building envelope elements. Although none of the redesigned elements are yet considered 100% circular, the development of these three prefabricated building envelope elements showcases that the environmental impact can be substantially reduced following a well-structured and dedicated innovation process. The reduction of the environmental impact is indicated by lower quantities of embodied carbon up to 50% and an improved design for disassembly, reflecting a higher reuse potential of building materials and components. Several limitations and directions for further research were identified to advance the development of circular, prefabricated deep-renovation building envelope elements.

Background Antibacterial therapy plays a crucial role in neonatal infections. The efficacy of antibacterial agents is closely related to the actual dose given to neonates. So we evaluated factors potentially affecting the actual dose of intravenous antibiotics during dispensing process in neonates.Methods Meropenem, cefoperazone/sulbactam and piperacillin/tazobactam with two strengths were used to evaluate three methods. Method A (MA) was diluted once and the volumes of 5% glucose for MA were meropenem 4.00 mL, cefoperazone/sulbactam 3.00 mL, piperacillin/tazobactam 9.00 mL. Method B (MB) differed by doubling the volume of 5% glucose. The difference in method C (MC) involved diluting with 5% glucose twice. The concentrations were measured by high-performance liquid chromatography. Relative error (RE) was used to evaluate the preparation accuracy.Results The RE values using MA/MB/MC were: (1) meropenem 0.5 g: 15.1%, 8.0%, 10.4%; 0.25 g: 7.8%, 3.1%, 6.0%; (2) cefoperazone/sulbactam 1.5 g: 13.6%, 4.2%, 3.4%; 0.75 g: 8.8%, 3.5%, 4.0%; (3) piperacillin/tazobactam 4.5 g: 18.2%, 8.7%, 6.3%; 562.5 mg: 8.1%, 2.8%, 6.1%. MB was better than MA in all three drugs. No difference in RE values was found between single and double dilution, except meropenem with 0.25 g. Using MB, meropenem and piperacillin/tazobactam with small drug strength had higher accuracy in preparation.Conclusions MB was suitable for neonatal drug dispensing because of its high accuracy and simple operation. Drugs with small strength were promoted due to the high accuracy.