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Abstract Background Severe psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision. Methods We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach. Discussion This individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments. Systematic review registration PROSPERO CRD42023402365.

Abstract Background Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia. Methods We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel–Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach. Discussion Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients. Systematic review registration PROSPERO-ID CRD42023410645.

Abstract The necessary separation of anodic and cathodic compartments in the electrochemical multicomponent synthesis of alkyl arenesulfonates in batch was overcome by the transfer of this reaction in an undivided electrochemical flow cell. The yield was increased from an initial 23 % to 67 % by optimization using Design of Experiments (DoE). The experiments were carried out using an automated experimental flow electrolysis setup controlled by the automation software LABS (Laboratory Automation and Batch Scheduling), an open‐source software that allows to plan and conduct experiments with an arbitrary, freely selectable experimental setup. The automated experimental setup turned out to be stable and provides reproducible results. In total, 6 examples are demonstrated with isolated yields up to 81 %. In addition, the robust scalability of the electrochemical reaction was demonstrated in a 10‐fold scale‐up.

Abstract A recent meta-epidemiological study did not reveal major differences between the results of blinded and open randomised-controlled trials (RCTs). Fewer patients may consent to double-blind RCTs than to open RCTs, compromising generalisability, making this question very important. However, the issue has not been addressed in schizophrenia. We used a database of randomised, acute-phase antipsychotic drug trials. Whenever at least one open and one blinded RCT was available for a comparison of two drugs, we contrasted the results by random-effects meta-analysis with subgroup tests. The primary outcome was overall symptoms as measured by the Positive and Negative Syndrome Scale, supplemented by seven secondary efficacy and side-effect outcomes. We also examined whether open RCTs were biased in favour of more recently introduced antipsychotics, less efficacious or more prone to side-effects antipsychotics, and pharmaceutical sponsors. 183 RCTs (155 blinded and 28 open) with 34715 participants comparing two active drugs were available. The results did not suggest general differences between open and blinded RCTs, which examined two active drugs. Only 12 out of 122 subgroup tests had a p-value below 0.1, four below 0.05, and if a Bonferroni correction for multiple tests had been applied, only one would have been significant. There were some exceptions which, however, did not always confirm the originally hypothesized direction of bias. Due to the relatively small number of open RCTs, our analysis is exploratory, but this fundamental question should be given more scientific attention. Currently, open RCTs should be excluded from meta-analyses, at least in sensitivity analyses.

Abstract Temperature sensors are one of the most fundamental sensors and are found in industrial, environmental, and biomedical applications. The traditional approach of reading the resistive response of Positive Temperature Coefficient thermistors at DC hindered their adoption as wide-range temperature sensors. Here, we present a large-area thermistor, based on a flexible and stretchable short carbon fibre incorporated Polydimethylsiloxane composite, enabled by a radio frequency sensing interface. The radio frequency readout overcomes the decades-old sensing range limit of thermistors. The composite exhibits a resistance sensitivity over 1000 °C−1, while maintaining stability against bending (20,000 cycles) and stretching (1000 cycles). Leveraging its large-area processing, the anisotropic composite is used as a substrate for sub-6 GHz radio frequency components, where the thermistor-based microwave resonators achieve a wide temperature sensing range (30 to 205 °C) compared to reported flexible temperature sensors, and high sensitivity (3.2 MHz/°C) compared to radio frequency temperature sensors. Wireless sensing is demonstrated using a microstrip patch antenna based on a thermistor substrate, and a battery-less radio frequency identification tag. This radio frequency-based sensor readout technique could enable functional materials to be directly integrated in wireless sensing applications.

Abstract Background The relative treatment effects estimated from network meta-analysis can be employed to rank treatments from the most preferable to the least preferable option. These treatment hierarchies are typically based on ranking metrics calculated from a single outcome. Some approaches have been proposed in the literature to account for multiple outcomes and individual preferences, such as the coverage area inside a spie chart, that, however, does not account for a trade-off between efficacy and safety outcomes. We present the net-benefit standardised area within a spie chart, $$SAWIS$$ SAWIS to explore the changes in treatment performance with different trade-offs between benefits and harms, according to a particular set of preferences. Methods We combine the standardised areas within spie charts for efficacy and safety/acceptability outcomes with a value λ specifying the trade-off between benefits and harms. We derive absolute probabilities and convert outcomes on a scale between 0 and 1 for inclusion in the spie chart. Results We illustrate how the treatments in three published network meta-analyses perform as the trade-off λ varies. The decrease of the $$SAWIS$$ SAWIS quantity appears more pronounced for some drugs, e.g. haloperidol. Changes in treatment performance seem more frequent when SUCRA is employed as outcome measures in the spie charts. Conclusions $$SAWIS$$ SAWIS should not be interpreted as a ranking metric but it is a simple approach that could help identify which treatment is preferable when multiple outcomes are of interest and trading-off between benefits and harms is important.

Additively manufactured mechanical metamaterials are gaining prominence in lightweight energy-absorption applications due to their exceptional mass-specific properties. Herein, we examine the energy absorption characteristics of micro-architected truss-, shell- and plate-lattice structures, namely, Octet, Kelvin, Gyroid, SC, BCC and FCC over a range of relative densities under quasi-static compression via both experiments and finite element analysis (FEA). Employing different 3D printing methods, namely, Digital Light Processing, Selective Laser Sintering and Material Jetting, the lattices were fabricated using PlasGray™ (photo-resin based plastic), PA12 (Nylon) and VeroWhite (photo-resin based rigid plastic) respectively. Our results indicate that the SC lattice structure outperforms in terms of stiffness and strength, while the Gyroid lattice outperforms in terms of energy absorption efficiency (η). At lower relative densities (

Despite extensive sorting, packaging waste often contains a mixture of different materials that make high-quality recycling difficult, especially in the case of flexible packaging. This is partly due to the widespread use of multi-layer laminates and packaging consisting of different inseparably combined materials. To improve the post-consumer recyclate quality and develop optimised recycling processes, it is important to generate a comprehensive understanding of the composition of the sorted packaging waste streams. Therefore, in this study, polyolefin sorting fractions for flexible packaging waste from three European countries are analysed in detail. By selective extraction of the different plastics, their mass fractions in the waste streams are determined. This shows that the PE-rich sorting fractions for flexible packaging are made up of 85–90% of PE, but also contain a certain proportion of foreign materials. A detailed analysis of the layer structures of various types of packaging also provides information on the prevalence of multi-layer packaging and the polymer and non-polymer materials used therein. This shows that particularly in food packaging, with 63–84% of multi-layer and 50–70% of multi-material packaging, a high proportion of foreign materials is used and introduced into the sorting fractions. These insights provide a valuable contribution to the development of recyclable packaging, potential sorting streams and recycling processes, especially with regard to the challenges of the closed-loop recycling of food packaging.

Abstract An electrochemical multicomponent synthesis of sulfonamides at room temperature in single‐pass flow is presented. In contrast to batch‐type electrolysis, an undivided flow cell setup with a stainless‐steel cathode and either a boron‐doped diamond (BDD) anode or a glassy carbon anode can be employed. Simply by using SO2 stock solutions, less atom‐economic sulfur dioxide surrogates can be avoided. Moreover, no additional supporting electrolytes are required due to the in‐situ generation of amidosulfinates, which also serve as intermediate for this transformation. This protocol allows sulfonamides to be synthesized directly from non‐prefunctionalized electron‐rich arenes with amines and SO2. In total, 10 examples are demonstrated with isolated yields up to 92 %. The robust scalability of this electrosynthesis with an easy downstream processing was also proven.

Abstract Background There is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, conventional pairwise meta-analyses will not be sufficient to inform this choice. To fill this gap, we will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomized controlled trials (RCTs) to rank antipsychotics according to their effect on cognitive functioning. Methods In our NMA, we will include RCTs in patients with schizophrenia or schizophrenia-like psychoses comparing one antipsychotic agent with another antipsychotic agent or placebo that measures cognitive function. We will include studies on patients of every age group, in any phase of illness (e.g., acute or stable, first episode or chronic schizophrenia, in- or outpatients) with an intervention time of at least 3 weeks. The primary outcome will be the composite score of cognitive functioning, preferentially measured with the test battery developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. The secondary outcomes include the seven cognitive domains that the composite score is composed of, as well as functioning and quality of life. Study selection and data extraction will be conducted by at least two independent reviewers. We will use the Cochrane Risk of Bias tool 2 to determine the risk of bias in studies, and we will evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). We will perform NMA using R (package netmeta). We will conduct subgroup and sensitivity analyses to explore the heterogeneity and assess the robustness of our findings. Discussion This systematic review and network meta-analysis aims to inform evidence-based antipsychotic treatment choice for cognitive deficits in schizophrenia patients by analyzing existing RCTs on this subject. The results have the potential to support patients’ and physicians’ decision-making processes based on the latest available evidence. Systematic review registration PROSPERO CRD42022312483

Abstract Novel low‐cost materials to uptake and detect vestigial amounts of pesticides are highly desirable for water quality monitoring. Herein, are demonstrated, for the first time, surface‐enhanced Raman scattering (SERS) sensors enabled via additively manufactured lattices coated with plasmonic nanoparticles (NPs) for detecting pesticides in real water samples. The architected lattices comprising polypropylene (PP) and multiwall carbon nanotubes (MWCNTs) are realized via fused filament fabrication (FFF). In the first stage, the SERS performance of the PP/MWCNT filaments coated with distinct metallic NPs (Ag NPs and Au NPs) is evaluated using methylene blue (MB) as molecular probe. Thereafter, distinctly architected hybrid SERS sensors with periodic porous and fully dense geometries are investigated as adsorbents to uptake MB from aqueous solutions and subsequent detection using SERS. The spatial distribution of MB and Ag NPs on the FFF‐printed lattices is accomplished by SERS imaging. The best hybrid composite is used as SERS probing system to detect low amounts of pesticides (thiram and paraquat) and offers a detection limit of 100 nm for both pesticides. As a proof‐of‐concept, FFF‐enabled test strips are used to detect in loco paraquat molecules spiked on real water samples (Estuary Aveiro water and tap water) using a portable Raman spectrometer.

In recent years, network meta-analyses have been increasingly carried out to inform clinical guidelines and policy. This approach is under constant development, and a broad consensus on how to carry out several of its methodological and statistical steps is still lacking. Therefore, different working groups might often make different methodological choices based on their clinical and research experience, with possible advantages and shortcomings. In this contribution, we will critically assess two network meta-analyses on the topic of pharmacological prevention of relapse in schizophrenia, carried out by two different research groups. We will highlight the implications of different methodological choices on the analysis results and their clinical–epidemiological interpretation. Moreover, we will discuss some of the most relevant technical issues of network meta-analyses for which there is not a broad methodological agreement, including the assessment of transitivity.

Laser surface texturing has proven beneficial in improving tribological performance in different lubrication regimes. However, the interaction between plateau roughness and surface texture remains to be further investigated, even though rough surfaces are common in engineering applications. In the present study, we investigated the frictional influence of surface texturing of ground surfaces under different lubrication conditions. Channel textures with different depths and area ratios were fabricated on ground surfaces, and their friction was tested in reciprocating tests. The experimental findings indicate that the textures caused increased friction for ground surfaces under boundary or mixed lubrication when the interface is well lubricated. Nevertheless, when the oil supply was limited, an up to 40% friction reduction was observed under test conditions.

Abstract Abrasive wear mechanisms—including two-body and three-body abrasion—dominate the performance and lifespan of tribological systems in many engineering fields, even of those operating in lubricated conditions. Bearing steel (100Cr6) pins and discs in a flat-on-flat contact were utilized in experiments together with 5 and 13 µm Al2O3-based slurries as interfacial media to shed light on the acting mechanisms. The results indicate that a speed-induced hydrodynamic effect occurred and significantly altered the systems’ frictional behavior in tests that were performed using the 5 µm slurry. Further experiments revealed that a speed-dependent hydrodynamic effect can lead to a 14% increase in film thickness and a decrease in friction of around 2/3, accompanied by a transition from two-body abrasion to three-body abrasion and a change in wear mechanism from microcutting and microploughing to fatigue wear. Surprisingly, no correlation could be found between the total amount of wear and the operating state of the system during the experiment; however, the wear distribution over pin and disc was observed to change significantly. This paper studies the influence of the hydrodynamic effect on the tribological mechanism of lubricated abrasive wear and also highlights the importance to not only consider a tribological systems’ global amount of wear.

Abstract Solutions for the generation of FAIR (Findable, Accessible, Interoperable, and Reusable) data and metadata in experimental tribology are currently lacking. Nonetheless, FAIR data production is a promising path for implementing scalable data science techniques in tribology, which can lead to a deeper understanding of the phenomena that govern friction and wear. Missing community-wide data standards, and the reliance on custom workflows and equipment are some of the main challenges when it comes to adopting FAIR data practices. This paper, first, outlines a sample framework for scalable generation of FAIR data, and second, delivers a showcase FAIR data package for a pin-on-disk tribological experiment. The resulting curated data, consisting of 2,008 key-value pairs and 1,696 logical axioms, is the result of (1) the close collaboration with developers of a virtual research environment, (2) crowd-sourced controlled vocabulary, (3) ontology building, and (4) numerous – seemingly – small-scale digital tools. Thereby, this paper demonstrates a collection of scalable non-intrusive techniques that extend the life, reliability, and reusability of experimental tribological data beyond typical publication practices.

Abstract Background There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD. Methods We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses. Results We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles. Limitations Most of the studies were inadequately powered (sample sizes of 20–80 participants), with short duration (8–13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms. Conclusions Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.

Introduction Guidelines recommend clozapine for treatment-resistant schizophrenia. However, meta-analysis of aggregate data (AD) did not demonstrate higher efficacy of clozapine compared with other second-generation antipsychotics but found substantial heterogeneity between trials and variation between participants in treatment effects. Therefore, we will conduct an individual participant data (IPD) meta-analysis to estimate the efficacy of clozapine compared with other second-generation antipsychotics while accounting for potentially important effect modifiers.Methods and analysis In a systematic review, two reviewers will independently search Cochrane Schizophrenia Group’s trial register (without restrictions in date, language or state of publication) and related reviews. We will include randomised controlled trials (RCTs) in participants with treatment-resistant schizophrenia comparing clozapine with other second-generation antipsychotics for at least 6 weeks. We will apply no restrictions in age, gender, origin, ethnicity or setting, but exclude open-label studies, studies from China, experimental studies and phase II of cross-over trials. IPD will be requested from trial authors and cross-check against published results. AD will be extracted in duplicate. Risk of bias will be assessed using Cochrane’s Risk of Bias 2 tool.The primary outcome will be overall symptoms of schizophrenia.We will synthesise results using random-effects meta-analysis and meta-regression methods in a 3-level Bayesian model. The model combines IPD with AD when IPD is not available for all studies, and include participant, intervention and study design characteristics as potential effect modifiers. The effect size measures will be mean difference (or standardised mean difference when different scales were used). Confidence in the evidence will be assessed using GRADE.Ethics and dissemination This project has been approved by the ethics commission of the Technical University of Munich (#612/21 S-NP). The results will be published open-access in a peer-review journal and a plain-language version of the results will be disseminated.If we need to amend this protocol, we will describe the change and give the rationale in a specific section in the resulting publication ‘Changes with respect to the protocol’.Systematic review registration PROSPERO (#CRD42021254986)

Herein, we report the mechanical and piezoresistive sensing performance of 3D printed auxetic nanocomposite structures composed of a high-density polyethylene (HDPE) matrix and multi-walled carbon nanotubes (MWCNTs). The multifunctional performance of MWCNT/HDPE auxetic structures were measured under tensile loading. The results indicate that by varying the MWCNT content, as well as the relative density and cell topology (S-shaped, Chiral and Re-entrant) of the structure, we can achieve a tunable piezoresistive response. The results indicate that the S-shaped cellular structure possesses superior mechanical and piezoresistive characteristics, reporting a gauge factor of 7.6 at 4 wt % MWCNT loading, which is ∼300% higher than those measured for the Re-entrant and Chiral structures. We also present an empirical scaling equation that relates the structure's sensitivity factor to its relative density. The findings of this study provide useful guidelines for the design and fabrication of self-sensing smart materials and structures with tunable sensitivity.

This study investigates the feasibility of establishing urine-derived tumor organoids from bladder cancer (BC) patients as an alternative to tissue-derived organoids. BC is one of the most common cancers worldwide and current diagnostic methods involve invasive procedures. Here, we investigated the potential of using urine samples, which contain exfoliated tumor cells, to generate urine-derived BC organoids (uBCOs). Urine samples from 29 BC patients were collected and cells were isolated and cultured in a three-dimensional matrix. The establishment and primary expansion of uBCOs were successful in 83% of the specimens investigated. The culturing efficiency of uBCOs was comparable to cancer tissue-derived organoids. Immunohistochemistry and immunofluorescence to characterize the uBCOs exhibited similar expressions of BC markers compared to the parental tumor. These findings suggest that urine-derived BC organoids hold promise as a non-invasive tool for studying BC and evaluating therapeutic responses. This approach could potentially minimize the need for invasive procedures and provide a platform for personalized drug screening. Further research in this area may lead to improved diagnostic and treatment strategies for BC patients.

Abstract Background Antipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking. Methods We will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group’s Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework. Discussion This systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians. Systematic review registration PROSPERO CRD42020175414

Background: Antipsychotics are the treatment of choice in the therapy of schizophrenia. These drugs can be associated with changes in heart rate, but this question has never been examined systematically. Objective: We aimed to analyse changes in heart rate during treatment with antipsychotics using the frequency of tachycardia and bradycardia events. Design: For this systematic review and meta-analysis, we included all randomized controlled trials for the acute treatment of schizophrenia comparing antipsychotics head-to-head or with placebo. Data Sources and Methods: We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform and ClinicalTrials.gov (last search June 2021). Two authors independently selected studies and extracted data. We conducted pairwise meta-analyses using a random-effects model. Outcomes were tachycardia and bradycardia events. Results: We found 469 trials meeting the inclusion criteria. Seventy-seven studies with 16,907 participants provided data on tachycardia or bradycardia events. We found no significant differences between antipsychotics and placebo or between antipsychotics for bradycardia events based on sparse data. Antipsychotics had a higher risk for tachycardia events compared with placebo [ N = 37, n = 7827, risk ratio (RR) = 1.83, 95% confidence interval (CI) = 1.40–2.41], with large differences between the individual substances (iloperidone RR = 14.05, chlorpromazine RR = 4.84, loxapine RR = 4.52, risperidone RR = 3.38, quetiapine RR = 2.64, paliperidone RR = 1.65). Some head-to-head comparisons were also significantly different: olanzapine versus haloperidol RR = 2.87, chlorpromazine versus thiothixene RR = 2.92, quetiapine versus lurasidone RR = 3.22, risperidone versus aripiprazole RR = 4.37, iloperidone versus ziprasidone RR = 4.65). Conclusion: Many studies do not report data for cardiac outcomes, but the available evidence indicates that treatment with antipsychotics raises the risk for tachycardia. Therefore, especially patients with cardiac risk factors should be monitored closely during antipsychotic treatment. Registration: PROSPERO: CRD42014014919

Abstract Herein we report a conceptually new non‐decarboxylative electrolysis of carboxylic acids to obtain their corresponding anhydrides as highly valuable reagents in organic synthesis. All carbon atoms of the starting material are preserved in the product in an overall redox‐neutral reaction. In a broad substrate scope of carboxylic acids the anhydrides are generated with high selectivity, which demonstrates the versatility of the developed method. Beneficially, no dehydrating reagents are required in comparison to conventional methods and the synthesis is based on uncritical starting materials using graphite and stainless steel as very inexpensive and eco‐friendly electrode materials.

In this paper, the process of an additive laser marking on stainless steel parts for barcode printing is presented. It is based on the use of one transition metal oxide chemically-well bonded to the stainless steel substrate, without a usage of any additional materials and cleaning substances. The resulting additive coatings, produced from initial MoO3 powder by irradiation with a laser beam, reveal strong adhesion, high hardness, long durability and high optical contrast, which make the process suitable for barcode printing on materials such as high reflective stainless steel, which was always a challenge for the classical laser marking technologies. The obtained bar patterns are in a compliance with the requirements of the existing standards.

Abstract Background Placebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms. Methods We searched ClinicalTrials.gov , CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019) for randomized pharmacological and dietary supplement placebo-controlled trials (RCTs) with a minimum of seven days of treatment. Single-group meta-analyses were conducted using a random-effects model. Standardized mean changes (SMC) of core symptoms in placebo arms were the primary outcomes and placebo positive response rates were a secondary outcome. Predictors of placebo response were investigated with meta-regression analyses. The protocol was registered with PROSPERO ID CRD42019125317 . Results Eighty-six RCTs with 2360 participants on placebo were included in our analysis (87% in children/adolescents). The majority of trials were small, single-center with a duration of 8–12 weeks and published after 2009. Placebo response in social-communication difficulties was SMC = − 0.32, 95% CI [− 0.39, − 0.25], in repetitive behaviors − 0.23[− 0.32, − 0.15] and in scales measuring overall core symptoms − 0.36 [− 0.46, − 0.26]. Overall, 19%, 95% CI [16–22%] of participants were at least much improved with placebo. Caregiver (vs. clinician) ratings, lower risk of bias, flexible-dosing, larger sample sizes and number of sites, less recent publication year, baseline levels of irritability, and the use of a threshold of core symptoms at inclusion were associated with larger placebo response in at least a core symptom domain. Limitations About 40% of the trials had an apparent focus on core symptoms. Investigation of the differential impact of predictors on placebo and drug response was impeded by the use of diverse experimental interventions with essentially different mechanisms of action. An individual-participant-data meta-analysis could allow for a more fine-grained analysis and provide more informative answers. Conclusions Placebo response in ASD was substantial and predicted by design- and participant-related factors, which could inform the design of future trials in order to improve the detection of efficacy in core symptoms. Potential solutions could be the minimization and careful selection of study sites as well as rigorous participant enrollment and the use of measurements of change not solely dependent on caregivers.

Abstract Background Depression is one of the leading causes of the global burden of disease, and it has particularly negative consequences for elderly patients. Antidepressants are the most frequently used treatment. We present the first single-group meta-analysis examining: 1) the response rates of elderly patients to antidepressants, and 2) the determinants of antidepressants response in this population. Methods We searched multiple databases for randomized controlled trials on antidepressants in the elderly with major depressive disorder above 65 years (last search: December 2017). Response was defined as 50% improvement on validated rating scales. We extracted response rates from studies and imputed the missing ones with a validated method. Data were pooled in a single-group meta-analysis. Additionally, several potential moderators of response to antidepressants were examined by subgroup and meta-regression analyses. Results We included 44 studies with a total of 6373 participants receiving antidepressants. On average, 50.7% of the patients reached a reduction of at least 50% on the Hamilton Depression Scale (HAMD). Subgroup and meta-regression analyses revealed a better response to treatment for patients in antidepressant-controlled trials compared to placebo-controlled trials. Mean age, study duration, percentage of woman, severity of illness at baseline, dose of antidepressants in fluoxetine equivalents, year of publication, setting (in- or out-patients), antidepressant groups (SSRI, TCA, SSNRI, α2-antagonist, SNRI, MAO-inhibitor), ITT (intention-to-treat) analysis vs completer analysis, sponsorship and overall risk of bias were not significant moderators of response. Conclusions Our findings suggest an improvement in symptoms can be found in about 50% of the elderly with major depressive disorder treated with antidepressants.

The influence of shipping on air quality over the Southern Baltic Sea was investigated by characterizing the horizontal and vertical distribution of aerosols and trace gases using airborne measurements in the summer of 2015. Generally, continental and anthropogenic emissions affected the vertical distribution of atmospheric pollutants, leading to pronounced stratification in and above the marine boundary layer and controlling the aerosol extinction. Marine traffic along the shipping corridor “Kadet Fairway” in the Arkona Basin is shown to influence the presence and properties of both trace gases and aerosol particles in the lowest atmospheric layer. Total particle number concentration and NOy mixing ratio increased in the corridor plumes, relative to background, by a factor 1.55 and 3.45, respectively. Titration, triggered by the enhanced presence of nitrogen compounds, led to a median ozone depletion of 19% in the corridor plumes. The enforcement of the Sulphur Emission Control Area (SECA) might be responsible for the minor sulphur dioxide increase (20%) in the corridor plumes. Ship traffic caused a minor enhancement of black carbon mass concentration, estimated to be around 10%. The study of individual ship plumes indicated that ship emitted aerosol was substantially different from background aerosol: fresh ship exhaust was preferentially enriched in aerosol particles with diameters below 100 nm and in black carbon particles with core diameters above 300-400 nm. With the present work the impact of marine traffic on the concentration and properties of atmospheric components within the marine boundary layer over the open water of the Southern Baltic Sea is assessed with airborne observations for the first time. Due to the high uncertainty affecting the estimations of ship emissions, this dataset represents a valuable reference for the assessment of ship emission inventories and related environmental-climatic impacts on the Southern Baltic Sea.

Accurate measurement of cortical bone parameters may improve fracture risk assessment and help clinicians on the best treatment strategy. Patients at risk of fracture are currently detected using the current X-Ray gold standard DXA (Dual XRay Absorptiometry). Different alternatives, such as 3D X-Rays, Magnetic Resonance Imaging or Quantitative Ultrasound (QUS) devices, have been proposed, the latter having advantages of being portable and sensitive to mechanical and geometrical properties. The objective of this cross-sectional study was to evaluate the performance of a Bi-Directional Axial Transmission (BDAT) device used by trained operators in a clinical environment with older subjects. The device, positioned at one-third distal radius, provides two velocities: VFAS (first arriving signal) and VA0 (first anti-symmetrical guided mode). Moreover, two parameters are obtained from an inverse approach: Ct.Th (cortical thickness) and Ct.Po (cortical porosity), along with their ratio Ct.Po/Ct.Th. The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. One hundred and six patients (81 women, 25 men) from Marien Hospital and St. Anna Hospital (Herne, Germany) were included in this study. Age ranged from 41 to 95 years, while body mass index (BMI) ranged from 16 to 47 kg.m-2. Three groups were considered: 79 non-fractured patients (NF, 75±13years), 27 with non-traumatic fractures (F, 80±9years) including 14 patients with non-vertebral fractures (NVF, 84±7years). Weak to moderate significant Spearman correlations (R ranging from 0.23 to 0.53, p < 0.05) were found between ultrasound parameters and age, BMI. Using multivariate Partial Least Square discrimination analyses with Leave-One-Out Cross-Validation (PLS-LOOCV), we found the combination of VFAS and the ratio Ct.Po/Ct.Th to be predictive for all non traumatic fractures (F) with the odds ratio (OR) equals to 2.5 [1.6-3.4] and the area under the ROC curve (AUC) equal to 0.63 [0.62-0.65]. For the group NVF, combination of four parameters VA0. Ct.Th, Ct.Po and Ct.Po/Ct.Po, along with age provides a discrimination model with OR and AUC equals to 7.5 [6.0-9.1] and 0.75 [0.73-0.76]. When restricted to a smaller population (87 patients) common to both BDAT and DXA, BDAT ORs and AUCs are comparable or slightly higher to values obtained with DXA. The fracture risk assessment by BDAT method in older patients, in a clinical setting, suggests the benefit of the affordable and transportable device for the routine use.

While the modification of surface contacts offers significant potential for friction reduction, obtaining an underlying consistent friction behaviour of real-life experiments and virtual simulations is still an ongoing challenge. In particular, most works in the literature only consider idealised geometries that can be parametrised with simple analytical functions. In contrast to this approach, the current work describes the establishment of a digital twin of a pin-on-disk tribometer whose virtual geometry is completely replicated from real-life post-test topography measurements and fed into a two-scale mixed lubrication solver. Subsequently, several calibration steps are performed to identify the sensitivities of the friction behaviour towards certain geometry features and enable the digital twin to robustly represent the Stribeck curve of the physical experiments. Furthermore, a derivation of the Hersey number is used to generalise the obtained friction behaviour for different dynamic viscosities and allow the validation of the presented method.

The use of genetic resources in breeding is considered critical to ensure future selection gain, but the absence of important adaptation genes often masks the breeding value of genetic resources for grain yield. Testing genetic resources in a hybrid background has been proposed as a solution to obtain unbiased estimates of breeding values for grain yield. In our study, we evaluated the suitability of European wheat elite lines for implementing this hybrid strategy, focusing on maximizing seed yield in hybrid production and reducing masking effects due to susceptibility to lodging, yellow rust, and leaf rust of genetic resources. Over a 3-year period, 63 wheat elite female lines were crossed with eight male plant genetic resources in a multi-environment field experiment to evaluate seed yield on the female side. Then, the resulting hybrids and their parents were tested for plant height, lodging, and susceptibility to yellow rust and leaf rust in a further field experiment at multiple locations. We found that seed yield was strongly influenced by the elite wheat line choice in addition to environment and observed substantial differences among elite tester lines in their ability to reduce susceptibility to lodging, yellow rust, and leaf rust when the hybrid strategy was implemented. Consequently, breeders can significantly increase the amount of hybrid seed produced in wide crosses through appropriate tester choice and adapt genetic resources of wheat with the hybrid strategy to the modern cropping system.

Abstract Background Cognitive behavioural therapy has been used for schizophrenia, but to which extent it is effective is still controversial. Results of existing meta-analyses are of difficult interpretation, because they mainly present effect sizes in the form of standardized mean differences between intervention and control groups based on rating scales, which are of unclear clinical meaning. No meta-analysis has considered the number of patients responding to treatment yet. Based on this ground, we present the first meta-analysis examining the response rates of patients with schizophrenia and positive symptoms to cognitive behavioural therapy. Methods We searched multiple databases for randomized controlled trials on psychological interventions of schizophrenia including patients with positive symptoms, and included for this analysis the studies on cognitive behavioural therapy (last search: January 2018). We applied a validated imputation method to calculate the number of responders from rating scales for the outcomes overall symptoms and positive symptoms, based on two criteria, at least 20% and at least 50% reduction from baseline on PANSS or BPRS total scores. Data were pooled in a single-group summary meta-analysis using R software. Additionally, several potential moderators of response to cognitive behavioural therapy were examined by subgroup and meta-regression analyses. The protocol has been registered in PROSPERO (CRD42017067795). Results We included 33 studies with a total of 1142 participants receiving cognitive behavioural therapy. On average, 44.5 and 13.2% of the patients reached a 20% (minimally improved) and 50% (much improved) reduction of overall symptoms. Similarly, 52.9 and 24.8% of the patients reached a 20%/50% reduction of positive symptoms. Subgroup and meta-regression analyses revealed a better treatment response in overall symptoms for patients that were not treatment resistant and in studies with researchers’ allegiance. Of borderline significance was the better response in studies employing expert therapists and in patients that were more severely ill at baseline. Blinding of outcome assessor, number of sessions, treatment duration, age and gender were not significant moderators of response. Conclusions Our findings suggest that adding cognitive behavioural therapy to pharmacotherapy brings about a minimal improvement in overall symptoms among 44.5% of its recipients. Several study and patients characteristics can moderate response rates.

Abstract Secondary organic aerosols (SOA) are large contributors to fine particle mass loading and number concentration and interact with clouds and radiation. Several processes affect the formation, chemical transformation, and removal of SOA in the atmosphere. For computational efficiency, global models use simplified SOA treatments, which often do not capture the dynamics of SOA formation. Here we test more complex SOA treatments within the global Energy Exascale Earth System Model (E3SM) to investigate how simulated SOA spatial distributions respond to some of the important but uncertain processes affecting SOA formation, removal, and lifetime. We evaluate model predictions with a suite of surface, aircraft, and satellite observations that span the globe and the full troposphere. Simulations indicate that both a strong production (achieved here by multigenerational aging of SOA precursors that includes moderate functionalization) and a strong sink of SOA (especially in the middle upper troposphere, achieved here by adding particle‐phase photolysis) are needed to reproduce the vertical distribution of organic aerosol (OA) measured during several aircraft field campaigns; without this sink, the simulated middle upper tropospheric OA is too large. Our results show that variations in SOA chemistry formulations change SOA wet removal lifetime by a factor of 3 due to changes in horizontal and vertical distributions of SOA. In all the SOA chemistry formulations tested here, an efficient chemical sink, that is, particle‐phase photolysis, was needed to reproduce the aircraft measurements of OA at high altitudes. Globally, SOA removal rates by photolysis are equal to the wet removal sink, and photolysis decreases SOA lifetimes from 10 to ~3 days. A recent review of multiple field studies found no increase in net OA formation over and downwind biomass burning regions, so we also tested an alternative, empirical SOA treatment that increases primary organic aerosol (POA) emissions near source region and converts POA to SOA with an aging time scale of 1 day. Although this empirical treatment performs surprisingly well in simulating OA loadings near the surface, it overestimates OA loadings in the middle and upper troposphere compared to aircraft measurements, likely due to strong convective transport to high altitudes where wet removal is weak. The default improved model formulation (multigenerational aging with moderate fragmentation and photolysis) performs much better than the empirical treatment in these regions. Differences in SOA treatments greatly affect the SOA direct radiative effect, which ranges from −0.65 (moderate fragmentation and photolysis) to −2 W m−2 (moderate fragmentation without photolysis). Notably, most SOA formulations predict similar global indirect forcing of SOA calculated as the difference in cloud forcing between present‐day and preindustrial simulations.

Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene.Methods: BDAT bone ultrasound was performed at the non-dominant distal radius (33% relative to distal head) and the central left tibia (50%) in eight XLH patients aged between 4.2 and 20.8 years and compared to twenty-nine healthy controls aged between 5.8 and 22.4 years. In eighteen controls, only radius measurements were performed. Four patients and four controls opted to participate in HR-pQCT scanning of the ultradistal radius and tibia.Results: Bone ultrasound was feasible in patients and controls as young as 4 years of age. The velocity of the first arriving signal (νFAS) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean νFAS of XLH patients and controls was 3599 ± 106 and 3866 ± 142 m/s, respectively (−6.9%; p < 0.001). In the tibia, it was 3578 ± 129 and 3762 ± 124 m/s, respectively (−4.9%; p = 0.006). HR-pQCT showed a higher trabecular thickness in the tibia of XLH patients (+16.7%; p = 0.021).Conclusions: Quantitative bone ultrasound revealed significant differences in cortical bone quality of young XLH patients as compared to controls. Regular monitoring of XLH patients by a radiation-free technology such as BDAT might provide valuable information on bone quality and contribute to the optimization of treatment. Further studies are needed to establish this affordable and time efficient method in the XLH patients.

Background Differentiating nonwear time from sleep and wake times is essential for the estimation of sleep duration based on actigraphy data. To efficiently analyze large-scale data sets, an automatic method of identifying these three different states is required. Therefore, we developed a classification algorithm to determine nonwear, sleep and wake periods from accelerometer data. Our work aimed to (I) develop a new pattern recognition algorithm for identifying nonwear periods from actigraphy data based on the influence of respiration rate on the power spectrum of the acceleration signal and implement it in an automatic classification algorithm for nonwear/sleep/wake states; (II) address motion artifacts that occur during nonwear periods and are known to cause misclassification of these periods; (III) adjust the algorithm depending on the sensor position (wrist, chest); and (IV) validate the algorithm on both healthy individuals and patients with sleep disorders. Methods The study involved 98 participants who wore wrist and chest acceleration sensors for one day of measurements. They spent one night in the sleep laboratory and continued to wear the sensors outside of the laboratory for the remainder of the day. The results of the classification algorithm were compared to those of the reference source: polysomnography for wake/sleep and manual annotations for nonwear/wear classification. Results The median kappa values for the two locations were 0.83 (wrist) and 0.84 (chest). The level of agreement did not vary significantly by sleep health (good sleepers vs. subjects with sleep disorders) (p = 0.348, p = 0.118) or by sex (p = 0.442, p = 0.456). The intraclass correlation coefficients of nonwear total time between the reference and the algorithm were 0.92 and 0.97 with the outliers and 0.95 and 0.98 after the outliers were removed for the wrist and chest, respectively. There was no evidence of an association between the mean difference (and 95% limits of agreement) and the mean of the two methods for either sensor position (wrist p = 0.110, chest p = 0.164), and the mean differences (algorithm minus reference) were 5.11 [95% LoA −15.4–25.7] and 1.32 [95% LoA −9.59–12.24] min/day, respectively, after the outliers were removed. Discussion We studied the influence of the respiration wave on the power spectrum of the acceleration signal for the differentiation of nonwear periods from sleep and wake periods. The algorithm combined both spectral analysis of the acceleration signal and rescoring. Based on the Bland-Altman analysis, the chest-worn accelerometer showed better results than the wrist-worn accelerometer.

Reducing friction forces is a major challenge in many engineering applications involving moving parts. For the past 50 years, the morphological texturing of surfaces for improving tribological properties has been investigated. Only recently, the application of biologically inspired surface features, like scales found on lizards and snakes, has come to the attention of tribologists. Here, we present results of the lubricated and unlubricated performance of biologically inspired scale-like textures applied with laser light to the surface of bearing steel pins. These were paired in unidirectional sliding against metallic (100Cr6), polymeric (PEEK) and ceramic (Al2O3) counter bodies. Additionally, a possible size effect was investigated by changing the scale diameter between 13 and 150 µm under dry sliding contact against sapphire. Our results demonstrate that depending on the contact conditions a biologically inspired surface morphology has the potential to reduce friction forces by more than 80%. However, under certain conditions, especially for slow-moving lubricated steel-on-steel and steel-on-ceramic contacts, these surface morphologies may increase friction as well. Similar to classical laser surface textures, such as round dimples, these biologically inspired morphologies need to be carefully optimized for each tribological system in which they are intended to be applied. There is no standard solution for all sliding conditions. The results presented here demonstrate that such efforts have the potential to yield significant reduction in friction forces and are expected to spark future research in the field of biologically inspired surface morphologies applied to tribological contacts.

The hazard to persons and structures derived from secondary explosion effects, associated with blast loads on structural components resulting in e.g. debris throw, may exceed the hazard range from the blast wave itself. The debris throw hazard potential is related to the initial fragment throw parameters as launch velocities, angles and masses during the structural failure. These parameters strongly depend on the overpressure characteristics of the explosion, controlled by the explosive amount and category resulting in either detonations (typically high-order explosives, e.g. TNT or ANFO) or deflagrations (typically low-order explosives, as e.g. gas-air mixtures or propellants). Detonation shock fronts are typically characterized by very fast propagation velocities (supersonic), high peak overpressures and a small spatial extent. In contrast, the deflagration shock front propagates much slower (subsonic) and is characterized by lower peak overpressures but a larger spatial extent. Understanding the break-up process during the structural failure and the resultant initial fragment throw characteristics, related to the loading conditions (explosive amount and category), is thus essential to assess the hazard potential from explosions and provide the basis for proper consequence modelling in risk analyses. However, the data basis for hazard assessment and model development on debris throw from masonry structures is still very limited. This contribution describes recent shock-tube experiments with the goal to characterize the hazard from single span masonry walls subjected to dynamic blast loads with pressure-time characteristics of typical high-order explosions. Based on stereo high-speed video images and computer vision techniques, we analysed the masonry break-up process and derived debris fragment trajectories, velocities, launch angles and mass distributions. Based on the observed debris throw characteristics, approaches for hazard assessment of masonry failure are described in order to discuss the transferability of the results with respect to the different loading characteristics of low-order explosions and the structural component.

Alterations of structure and density of cortical bone are associated with fragility fractures and can be assessed in vivo in humans at the tibia. Bone remodeling deficits in aging women have been recently linked to an increase in size of cortical pores. In this ex vivo study, we characterized the cortical microarchitecture of 19 tibiae from human donors (aged 69 to 94 years) to address, whether this can reflect impairments of the mechanical competence of the proximal femur, i.e., a major fracture site in osteoporosis. Scanning acoustic microscopy (12 μm pixel size) provided reference microstructural measurements at the left tibia, while the bone vBMD at this site was obtained using microcomputed tomography (microCT). The areal bone mineral density of both left and right femoral necks (aBMDneck) was measured by dual-energy X-ray absorptiometry (DXA), while homogenized nonlinear finite element models based on high-resolution peripheral quantitative computed tomography provided hip stiffness and strength for one-legged standing and sideways falling loads. Hip strength was associated with aBMDneck (r = 0.74 to 0.78), with tibial cortical thickness (r = 0.81) and with measurements of the tibial cross-sectional geometry (r = 0.48 to 0.73) of the same leg. Tibial vBMD was associated with hip strength only for standing loads (r = 0.59 to 0.65). Cortical porosity (Ct.Po) of the tibia was not associated with any of the femoral parameters. However, the proportion of Ct.Po attributable to large pores (diameter > 100 μm) was associated with hip strength in both standing (r = -0.61) and falling (r = 0.48) conditions. When added to aBMDneck, the prevalence of large pores could explain up to 17% of the femur ultimate force. In conclusion, microstructural characteristics of the tibia reflect hip strength as well as femoral DXA, but it remains to be tested whether such properties can be measured in vivo.

[This corrects the article DOI: 10.1371/journal.pone.0215405.].

Physisorbed water originating from exposure to the ambient can have a strong impact on the structure and chemistry of oxide nanomaterials. The effect can be particularly pronounced when these oxides are in physical contact with a solid substrate such as the ones used for immobilization to perform electron or ion microscopy imaging. We used helium ion microscopy (HIM) and investigated morphological changes of vapor-phase-grown MgO cubes after vacuum annealing and pressing into foils of soft and high purity indium. The indium foils were either used as obtained or, for reference, subjected to vacuum drying. After four days of storage in the vacuum chamber of the microscope and at a base pressure of p < 10−7 mbar, we observed on these cubic particles the attack of residual physisorbed water molecules from the indium substrate. As a result, thin magnesium hydroxide layers spontaneously grew, giving rise to characteristic volume expansion effects, which depended on the size of the particles. Rounding of the originally sharp cube edges leads to a significant loss of the morphological definition specific to the MgO cubes. Comparison of different regions within one sample before and after exposure to liquid water reveals different transformation processes, such as the formation of Mg(OH)2 shells that act as diffusion barriers for MgO dissolution or the evolution of brucite nanosheets organized in characteristic flower-like microstructures. The findings underline the significant metastability of nanomaterials under both ambient and high-vacuum conditions and show the dramatic effect of ubiquitous water films during storage and characterization of oxide nanomaterials.

Due to structural redundancy,strong energy absorption and energy dissipation capacity of nail joints,wood buildings behave good seismic performance in earthquakes. Cross laminated timber is a new generation of engineered wood-based product. Based on tests of three kinds of cross laminated timber connections,Pinching4 model in Open Sees as a user-defined element is applied to simulate the hysteresis response of the connections,which is highly nonlinear,strength degradation,stiffness degradation,and pinching. The primary and follower half-cycle energy damage model is used for damage quantitative analysis of the connections,and the damage factor ranges corresponding to five damage levels of cross laminated timber connections are given in this article. The study shows that good simulation results are obtained and it is also illustrated that Pinching4 model is valid and feasible to predict the hysteretic response of wood connections. Different damage factors responding to varied damage degrees are consistent with the experimental rules. The dispersion degrees of the damage factors are relatively low with the mean values in the reasonable ranges.

Cross laminated timber(CLT),a new generation of engineered wood-based product,is gaining attention in the North American market,but it has not been introduced and spread in China yet. In the paper,the mechanical properties of CLT are introduced in details,and the production technology,design methods and research progress are summarized as well. What's more,an experimental study on CLT flexible connection in seismic performance is done. The results show that the failure with all fasteners pulled out is disclosed as an ideal ductility failure. Highly nonlinear,stiffness degradation,strength degradation and pinching are illustrated in the hysteresis curves of connection. An excellent connector in ductility and load capacity is presented by test data analysis.

Background Muscarinic receptor agonism is a promising mechanism of action for treating psychosis, not present in most D 2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists in animal models of psychosis to provide unique insights and evidence-based information to guide drug development. Methods We plan a systematic review and meta-analysis of in vivo animal studies comparing muscarinic receptor agonists or positive allosteric modulators with control conditions and existing D2R-blocking antipsychotics in animals subjected to any method that induces behavioural changes of relevance for psychosis. We will identify eligible studies by searching multiple electronic databases. At least two independent reviewers will conduct the study selection and data extraction using prespecified forms and assess the risk of bias with the SYRCLE’s tool. Our primary outcomes include locomotor activity and prepulse inhibition measured with standardized mean differences. We will examine other behavioural readouts of relevance for psychosis as secondary outcomes, such as social interaction and cognitive function. We will synthesize the data using multi-level meta-analysis with a predefined random-effects structure, considering the non-independence of the data. In meta-regressions we will explore potential sources of heterogeneity from a predefined list of characteristics of the animal population, model, and intervention. We will assess the confidence in the evidence considering a self-developed instrument thatconsiders the internal and external validity of the evidence. Protocol registration PROSPERO-ID: CRD42024520914

Lipid rafts are membrane microdomains specialized in the regulation of numerous cellular processes related to membrane organization, as diverse as signal transduction, protein sorting, membrane trafficking or pathogen invasion. It has been proposed that this functional diversity would require a heterogeneous population of raft domains with varying compositions. However, a mechanism for such diversification is not known. We recently discovered that bacterial membranes organize their signal transduction pathways in functional membrane microdomains (FMMs) that are structurally and functionally similar to the eukaryotic lipid rafts. In this report, we took advantage of the tractability of the prokaryotic model Bacillus subtilis to provide evidence for the coexistence of two distinct families of FMMs in bacterial membranes, displaying a distinctive distribution of proteins specialized in different biological processes. One family of microdomains harbors the scaffolding flotillin protein FloA that selectively tethers proteins specialized in regulating cell envelope turnover and primary metabolism. A second population of microdomains containing the two scaffolding flotillins, FloA and FloT, arises exclusively at later stages of cell growth and specializes in adaptation of cells to stationary phase. Importantly, the diversification of membrane microdomains does not occur arbitrarily. We discovered that bacterial cells control the spatio-temporal remodeling of microdomains by restricting the activation of FloT expression to stationary phase. This regulation ensures a sequential assembly of functionally specialized membrane microdomains to strategically organize signaling networks at the right time during the lifespan of a bacterium.