Search

Abstract Background Only a few cases of bilateral traumatic sternoclavicular dislocations have been reported in the literature. This injury is considered one of the rarest injuries of the human musculoskeletal system. Therefore, we present the first documented case of a cyclist with a third-degree open thoracic trauma (Gustilo–Anderson 3a) associated with a dislocated manubrium sterni fracture in the upper thoracic aperture, bilateral anterior dislocations of the sternoclavicular joints, rib fractures, and pleural ruptures. Case presentation The patient, a 27-year-old Caucasian male, incurred this injury while participating in a professional cycling race at Nürburgring, Germany and received immediate interdisciplinary surgical treatment and has encountered no complications. We conducted a 1-year follow-up and present the clinical findings of this follow up. Additionally, we conducted a comprehensive review of the existing literature on this injury. Conclusions Immediate interdisciplinary intervention, including surgical repair and meticulous postoperative care, facilitated successful patient recovery. This underscores the critical role of comprehensive trauma management in complex polytrauma cases. In conclusion, this case report highlights the rarity and complexity of a traumatic injury involving bilateral sternoclavicular dislocation, with this case being the first case reported with concomitant open thorax trauma. Our patient benefited greatly from immediate air-bound transportation to an interdisciplinary care provider, which houses both thoracic and trauma surgery departments.

Abstract Purpose The goal of this retrospective study was to perform a CT imaging assessment of thoracic pedicles to provide a representative understanding of pedicle morphology for pedicle-based fixation systems commonly used in orthopedics, trauma and neurosurgery. This study aimed to better understand the morphology of the spine and give spine surgeons a better understanding of thoracic spine anatomy. Methods In this study, we retrospectively measured the thoracic spine pedicles of a total of 16 males and 16 females, totaling in 768 individual pedicles. For the measurements, we used standardized planes in computed tomography imaging with a maximum slice thickness of 1 mm. Results In brief, we identified significant differences in various measurements of male and female pedicle morphology. The medial cortical wall of the pedicles was significantly thicker than the lateral wall, and, in both sexes, the thoracic vertebral body number four was the vertebra with the least amount of cortical bone in the pedicle. Conclusions Surgeons performing operations involving pedicle screw placement should be aware of the sex-specific differences in thoracic spine pedicle morphology noted in this research.

Background/purpose: To investigate a quantitative method for assessing image quality of low dose lung computed tomography (CT) and find the lowest exposure dose providing diagnostic images. Methods: Axial volumetric lung CT acquisitions (256 slice scanner) were performed on three different sized anthropomorphic phantoms at different dose levels. The maximum steepness of sigmoid curves fitted to line density profiles was measured at lung-to-pleura interfaces. For each phantom, image sharpness was calculated as the median of 468 measurements from 39 different locations. Diagnostic image quality for the adult and paediatric phantom was rated by three radiologists using 4-point Likert scales. The image sharpness cut-off for obtaining adequate image quality was determined from qualitative ratings. Results: Adequate diagnostic image quality was reached at a median steepness of 713 HU/mm in the adult phantom with a corresponding CTDIvol of 0.14 mGy and an effective dose of 0.13 mSv at a dose level of 100 kVp and 10 mA. In the paediatric phantom diagnostic image quality was reached at a median steepness of 1139 HU/mm with a corresponding CTDIvol of 0.13 mGy and an effective dose of 0.08 mSv at a dose level of 100 kVp and 10 mA. Conclusions: Determination of image sharpness on line density profiles can be used as quantitative measure for image quality of lung CT. Sufficient-quality lung CT can be achieved at effective radiation doses of 0.13 mSv (adult phantom) and 0.08 mSv (paediatric phantom). These findings suggest that substantial dose reduction is feasible without compromising diagnostic accuracy.

Die Anwendung von pädagogischer Diagnostik benötigt sowohl konzeptuelles als auch strategisches Wissen über diagnostische Entscheidungsprozesse. Um diese Entscheidungsprozesse für die Ausbildung im Lehramt Sonderpädagogik der Hochschule möglichst anwendungsbezogen nachzustellen, wurde ein digitales fallbasiertes Simulationsspiel entwickelt. Ziel ist es, angehende Sonderpädagog:innen im Studium zu ökonomischen diagnostischen Entscheidungen im Rahmen pädagogischer Diagnostik zu befähigen und den Aufbau von Handlungsschablonen zu fördern. Diese Studie untersucht mittels Learning Analytics, inwieweit die Simulationsspiele zur Weiterentwicklung der diagnostischen Entscheidungskompetenz von Studierenden (N = 30) beitragen. Untersucht wird, wie treffsicher und effizient Studierende aus fünf Testverfahren den jeweils passenden Test auswählen. Der wiederholte Einsatz der Simulationsspiel führt zu signifikanten Veränderungen in der Entscheidungsheuristik. Studierende treffen ihre Entscheidungen nach der Übung mit durchschnittlich 2,1 Tests und einer Treffsicherheit von 41,39%. Die Einsatzmöglichkeiten und der Mehrwert von digitalen Simulationsspielen wird für die Lehrer:innenausbildung diskutiert. Abstract It is essential that teachers possess a comprehensive understanding of the conceptual and strategic aspects of the diagnostic decision-making process. A digital case-based simulation game was developed with the objective of enabling prospective special education students to make economic diagnostic decisions in the context of educational diagnostics and to promote the development of action templates. This study employs learning analytics to ascertain the extent to which the simulation games contribute to the further development of the diagnostic decision-making skills of students (N = 30). The study examines the accuracy and efficiency with which students select the appropriate test from five test procedures. Repeated use of the simulation game leads to significant changes in decision-making heuristics. Students make their decisions after the intervention with an average of 2.1 tests and an accuracy of 41.39%. The added value of digital simulation games in teacher training is discussed.

The "Cubes and Clouds" Massive Open Online Course (MOOC) addresses the growing challenges and opportunities in Earth Observation (EO) data analysis posed by the exponential growth of satellite missions and data volumes. This course introduces cloud-native EO concepts and open science principles, facilitating collaboration and data sharing within the EO community.Key topics covered in the MOOC include data discovery, processing workflows, and data sharing using real-world examples like snow cover mapping in the Alps. Participants engage with interactive lessons, videos, and hands-on coding exercises, leveraging freely available geospatial data and emphasizing open data principles and interoperability.The course infrastructure seamlessly integrates with cloud platforms like the Copernicus Data Space Ecosystem, enabling learners to apply concepts in a practical, cloud-based environment. Initial user statistics indicate strong interest, particularly among early-career professionals and researchers, with participant surveys suggesting increased confidence in using EO cloud platforms and embracing open science practices upon course completion.Overall, "Cubes and Clouds" serves as a valuable resource for the EO community, fostering transparency, collaboration, and innovation in geospatial science. Future developments aim to expand course content and attract diverse user groups, ensuring broader accessibility and long-term impact in advancing cloud-native EO and open science initiatives.

Background: Germany’s high density of under-equipped hospitals and anticipated surge in orthopedic and trauma surgery-related diseases by 2030, combined with personnel shortages, are expected to increase patient transfers between hospitals, an issue that urgently needs standardized protocols. Despite some existing cooperative agreements, such as between joint-replacement centers or within the Trauma Network DGU®, these measures do not adequately address the full range of patient-transfer cases, including those due to a lack of specialization or staff shortages, resulting in delayed treatment and potential health risks. This study aims to dissect the intricacies of interhospital transfers in orthopedics and trauma surgery across Germany, focusing on understanding the underlying reasons for transfers, comparing the operational structures of small and large hospitals, and laying the groundwork for future standardized protocols to enhance patient care. Material and Methods: A cross-sectional study was conducted in the form of an online survey via SoSci Survey, which was directed at orthopedic surgeons and trauma surgeons working in hospitals in Germany. The 22-question survey gathered information on participants’ clinic roles, departmental details, transfer processes, frequent diagnoses, perceptions of transfer quality, and improvement areas. The survey was sent to orthopedic and trauma surgeons in Germany by the specialist society. The data were analyzed using descriptive and inferential statistics to ensure a comprehensive insight into interhospital transfer practices. Results: The study involved 152 participants from various hospital ranks and located in different hospital sizes and types across rural and urban areas. A significant difference was observed between the care structures of basic/regular care and central/maximum care hospitals, especially regarding the available facilities and specialties. These findings suggest improvements such as better patient documentation, increased digital communication, optimized patient distribution, and standardization of transfer requests, among others. Conclusions: This study highlights the urgent need for improved protocols and resource allocation to eliminate inequalities in transfers between hospitals in orthopedics and trauma surgery in Germany.

Abstract Purpose The purpose of this study was to evaluate the perspective of orthopaedic surgeons on the impact of artificial intelligence (AI) and to evaluate the influence of experience, workplace setting and familiarity with digital solutions on views on AI. Methods Orthopaedic surgeons of the AGA Society for Arthroscopy and Joint Surgery were invited to participate in an online, cross‐sectional survey designed to gather information on professional background, subjective AI knowledge, opinion on the future impact of AI, openness towards different applications of AI, and perceived advantages and disadvantages of AI. Subgroup analyses were performed to examine the influence of experience, workplace setting and openness towards digital solutions on perspectives towards AI. Results Overall, 360 orthopaedic surgeons participated. The majority indicated average (43.6%) or rudimentary (38.1%) AI knowledge. Most (54.5%) expected AI to substantially influence orthopaedics within 5–10 years, predominantly as a complementary tool (91.1%). Preoperative planning (83.8%) was identified as the most likely clinical use case. A lack of consensus was observed regarding acceptable error levels. Time savings in preoperative planning (62.5%) and improved documentation (81%) were identified as notable advantages while declining skills of the next generation (64.5%) were rated as the most substantial drawback. There were significant differences in subjective AI knowledge depending on participants' experience (p = 0.021) and familiarity with digital solutions (p

As the International Archive of Women in Architecture (IAWA) completes its fourth decade in operation it pauses to reflect on its original goals within the context from which it emerged, as one initiative amongst many, in the quest to preserve the legacy of women in architecture. The IAWA seeks not only to better understand its role in the present context but also to reimagine its contribution to an equitable future, presenting here a proposition.

IntroductionSurgical glove use may be associated with a decrease in tactile sensitivity, with thicker gloves or double-gloving techniques further altering sensation. This study evaluates digital tactile sensitivity by use of a Grating Orientation Task (GOT) with multiple sterile gloving techniques (no gloves, single standard gloving, double standard gloving, orthopedic gloves, and micro-thickness gloves).MethodsEach participant performed the GOT at increasing grating widths until correctly noting orientation in ≥8 of 10 trials with multiple glove types or double-gloving technique. Glove order was randomly assigned and participants were blinded to the orientation and dome size.ResultsAll gloves except micro-thickness gloves showed increased threshold sensitivity values (i.e. worse fingertip sensitivity) when compared to control (micro:control, p = 0.105, others:control, p < 0.05). Single-layer gloves showed no significant difference in sensitivity when compared to orthopedic (p = 0.06) or double-layer latex gloves (p = 0.26).DiscussionStandard latex gloves decreased fingertip sensitivity when evaluated with the GOT. Double-layer and orthopedic latex gloves do not decrease sensitivity when compared with single-layer gloving. Micro-thickness gloves may provide similar tactile sensitivity to no surgical glove.

Abstract Ischemic stroke is a major global health issue and characterized by acute vascular dysfunction and subsequent neuroinflammation. However, the relationship between these processes remains elusive. In the current study, we investigated whether alleviating vascular dysfunction by restoring vascular nitric oxide (NO) reduces post-stroke inflammation. Mice were subjected to experimental stroke and received inhaled NO (iNO; 50 ppm) after reperfusion. iNO normalized vascular cyclic guanosine monophosphate (cGMP) levels, reduced the elevated expression of intercellular adhesion molecule-1 (ICAM-1), and returned leukocyte adhesion to baseline levels. Reduction of vascular pathology significantly reduced the inflammatory cytokines interleukin-1β (Il-1β), interleukin-6 (Il-6), and tumor necrosis factor-α (TNF-α), within the brain parenchyma. These findings suggest that vascular dysfunction is responsible for leukocyte adhesion and that these processes drive parenchymal inflammation. Reversing vascular dysfunction may therefore emerge as a novel approach to diminish neuroinflammation after ischemic stroke and possibly other ischemic disorders.

Background: Toxicological analysis of patients with acute recreational drug poisoning can improve our understanding of substance use patterns, clinical symptoms, and improve treatment. Patient history alone may be incomplete or misleading. The objective was to assess the differences in patient history and analytical results, to describe the clinical characteristics, implications and hospital management, and to describe the drug use pattern over time. Methods: A retrospective study including all patients admitted to our toxicology unit with recreational drug toxicity and analytical testing from October 2014 to December 2022. Results: 872 patients were included. Patient history revealed a median of one ingested substance class: opiates/opioids, benzodiazepines/Z-drugs, and Pregabalin were predominant. Urine analysis revealed a median of three ingested substance classes (p < 0.001). Benzodiazepines/Z-drugs, Pregabalin, and THC were severely underreported. Agitation and aggression, anxiety, hallucinations, and psychosis were frequent, associated with cocaine, cathinone/phenethylamine, and amphetamine/MDMA detection and required sedation. Coma was also frequent, associated with opiate/opioid, benzodiazepine/Z-drug, GBL/GHB, and Pregabalin detection and required intubation, and/or application of Naloxone and/or Flumazenil. Twelve patients arrived in cardiac arrest; all were positive for opiates/opioids. Four patients died: three with Benzodiazepines/Z-drugs, Pregabalin and opiates/opioids detected, one with cathinones/phenethylamines detected. While cathinones/phenethylamines and synthetic cannabinoid receptor agonists were mainly detected between 2014–2016, detection decreased significantly between 2017–2022 after NPS legislation passed. Pregabalin detection increased. Conclusions: Patient history is inaccurate, and patients frequently underreport ingested drugs. Opiates and opioids are still the main cause of morbidity and mortality. Pregabalin is increasingly abused. NPS legislation effectively decreased cathinone/phenethylamine and synthetic cannabinoid receptor agonist overdoses.

We report on a 14-year-old patient who was supported for nearly two years with an ic-LVAD and managed to complete his journey to transplantation without a single complication. Although mechanical assist device support is available for children up to 20 kg in body weight, availability is limited to paracorporeal devices. Intracorporal (ic) left ventricular assist devices (LVADs) for infants in the suitable weight class are a viable option as a bridge-to-transplant, where they make up more than 50% of transplant candidates in their category. A teenager with 59 kg body weight was newly diagnosed with DCM and listed for heart transplantation. After initially being on VA-ECMO, an Abbott HeartMate 3 LVAD with postoperative temporary RVAD support was initialised. RV-support was maintained for 10 days. The further postoperative course was uneventful, and he was discharged on day 98. He was seen regularly in the outpatient department and integrated into school routine again, following the extensive training of his classmates and the responsible school staff. After a total of 672 days on support, he was successfully transplanted. There were no unplanned admissions, thrombotic nor bleeding events, as well as no driveline infection, even though the patient participated in sport classes at school.

Green infrastructure is often proposed to complement conventional urban stormwater management systems that are stressed by extreme storms and expanding impervious surfaces. Established hydrological and hydraulic models inform stormwater engineering but are time- and data-intensive or aspatial, rendering them inadequate for rapid exploration of solutions. Simple spreadsheet models support quick site plan assessments but cannot adequately represent spatial interactions beyond a site. The present study builds on the Landscape Green Infrastructure Design (L-GrID) Model, a process-based spatial model that enables rapid development and exploration of green infrastructure scenarios to mitigate neighborhood flooding. We first explored how well L-GrID could replicate flooding reports in a neighborhood in Chicago, Illinois, USA, to evaluate its potential for green infrastructure planning. Although not meant for prediction, L-GrID was able to replicate the flooding reported and helped identify strategies for flood control. Once evaluated for this neighborhood, we extended the model to include water quality through the representation of dispersion and settling mechanisms for two pollutant surrogates—total nitrogen and total suspended solids. With the extended model, Landscape Green Infrastructure Design Model-Water Quality (L-GrID-WQ), we examined benefits, costs, and tradeoffs for different green infrastructure strategies. Bioswales were slightly more effective than other green infrastructure types in reducing flooding extent and downstream runoff and pollution, through increased infiltration and settling capacity. Permeable pavers followed in effectiveness and are suggested where spatial constraints may limit the installation of bioswales. Although green infrastructure supports both flooding and pollution control, small tradeoffs between these functions emerged across spatial layouts: strategies based on only curb-cuts better controlled pollution, while layouts that followed the path of water flow better controlled flooding. By illuminating such tradeoffs, L-GrID-WQ can support green infrastructure planning that prioritizes unique concerns in different areas of a landscape.

Abstract FIP200 plays important roles in homeostatic processes such as autophagy and signaling pathways such as focal adhesion kinase (FAK) signaling. Furthermore, genetic studies suggest an association of FIP200 mutations with psychiatric disorders. However, its potential connections to psychiatric disorders and specific roles in human neurons are not clear. We set out to establish a human-specific model to study the functional consequences of neuronal FIP200 deficiency. To this end, we generated two independent sets of isogenic human pluripotent stem cell lines with homozygous FIP200KO alleles, which were then used for the derivation of glutamatergic neurons via forced expression of NGN2. FIP200KO neurons exhibited pathological axonal swellings, showed autophagy deficiency, and subsequently elevated p62 protein levels. Moreover, monitoring the electrophysiological activity of neuronal cultures on multi-electrode arrays revealed that FIP200KO resulted in a hyperactive network. This hyperactivity could be abolished by glutamatergic receptor antagonist CNQX, suggesting a strengthened glutamatergic synaptic activation in FIP200KO neurons. Furthermore, cell surface proteomic analysis revealed metabolic dysregulation and abnormal cell adhesion-related processes in FIP200KO neurons. Interestingly, an ULK1/2-specific autophagy inhibitor could recapitulate axonal swellings and hyperactivity in wild-type neurons, whereas inhibition of FAK signaling was able to normalize the hyperactivity of FIP200KO neurons. These results suggest that impaired autophagy and presumably also disinhibition of FAK can contribute to the hyperactivity of FIP200KO neuronal networks, whereas pathological axonal swellings are primarily due to autophagy deficiency. Taken together, our study reveals the consequences of FIP200 deficiency in induced human glutamatergic neurons, which might, in the end, help to understand cellular pathomechanisms contributing to neuropsychiatric conditions.

The increasing availability of long-term observational data can lead to the development of innovative modelling approaches to determine landslide triggering conditions at a regional scale, opening new avenues for landslide prediction and early warning. This research blends the strengths of existing approaches with the capabilities of generalized additive mixed models (GAMMs) to develop an interpretable approach that identifies seasonally dynamic precipitation conditions for shallow landslides. The model builds upon a 21-year record of landslides in South Tyrol (Italy) and separates precipitation that induced landslides from precipitation that did not. The model accounts for effects acting at four temporal scales: short-term “triggering” precipitation, medium-term “preparatory” precipitation, seasonal effects, and across-year data variability. It provides relative landslide probability scores that were used to establish seasonally dynamic thresholds with optimal performance in terms of hit and false-alarm rates, as well as additional thresholds related to user-defined performance scores. The GAMM shows a high predictive performance and indicates that more precipitation is required to induce a landslide in summer than in winter/spring, which can presumably be attributed mainly to vegetation and temperature effects. The discussion illustrates why the quality of input data, study design, and model transparency are crucial for landslide prediction using advanced data-driven techniques.

As educators grapple with the impact of generative artificial intelligence (AI) and the ease of access to these models by learners, questions of pedagogy and learning have dominated the conversation. This paper explores the concerns of teaching through exploring the contrast between human and machine learning and the implications of both on educators facing an environment where AI is prevalent. Through a prompting process, a position paper was generated by ChatGPT3.5 on these contrasts and implications. The AI output, largely accurate, highlighted strategies for educators while also showcasing the limitations of the tool. Educators and scholars can support themselves and their students through critical reflection of the use of AI tools.

Various modifications of proteins and the resulting proteoforms of a protein can associate with many diseases and are also significantly involved in the rapid regulation of hemostasis and thrombosis. For example, the release of prostacyclin from the intact endothelium and the consequent following phosphorylation of VASP in platelets is a post-translational regulation to keep them in a quiescent state. In Alzheimer’s disease, proteoforms arise from the altered cleavage of the amyloid precursor protein, which finally causes amyloid plaques in the brain. This changed processing of the amyloid precursor protein can also be detected in platelets, making them an attractive source of biomarkers for this neurodegenerative disease. Age-related or prothrombotic disorders can have multiple origins, including genomic, transcriptional, and translational factors, which together can be mapped at the proteome level. Hence, recording these dynamic protein changes under physiological and pathophysiological conditions is paramount in platelet proteomics. To effectively study diseases through platelet proteomics, it is crucial to consider platelets’ primary regulatory mechanism and thoroughly evaluate the disparities between the two leading proteomics technologies, top-down and bottom-up approaches. This commentary provides insights into the differences between these two technologies, which are particularly noticeable in detecting the different proteoforms of a protein.

Data now plays a central role in civic life and community practices. This has created a pressing need for new forms of translation and sense-making that can engage diverse publics. Research-based Theatre (RbT) has proven to be an effective approach to delivering qualitative data to community stakeholders. We extend this tradition by proposing “community-engaged data theatre”. This approach translates quantitative data into theatrical language to engage communities in deliberative conversations on relevant issues. Community-engaged data theatre requires bridging multiple disciplines and involves creating new definitions and shared vocabularies in discourses that formerly have had little overlap in meaning. In this article, we share key insights from our initial experiments in which we adapted quantitative and qualitative data to devise a pilot piece in collaboration with a local community partner. In this essay, we communicate our collaborative process in polyvocal, artistic form. We edit and adapt materials from our conversations and creative practices into scenes illustrating how we taught and learned from each other about data science, participatory modeling, material deliberation and Composition to pilot our lab’s first community-engaged data theatre prototype.

Autophagy is known to impact CD4+ T cell proliferation but the identity of autophagosomal components remain unclear. Here the authors leverage a transgenic mouse model to assess the autophagosomal compartment and identify interleukin-7 receptor-α as a key cargo in proliferating CD4+ T cells.

Abstract Objective To identify the psychiatric profile of patients hospitalized due to self-intoxication associated with suicide-related behavior (SRB). Methods In this retrospective single-center study, records of consecutive patients treated for suicidal poisoning in our Clinical Toxicology unit between 1st January 2012 and 31st December 2016, who received at least one psychiatric exploration during their inpatient stay, were analyzed with regard to epidemiological data, ingested substances, psychiatric and somatic comorbidities, suicidal circumstances and follow-up therapy. Results Out of 1289 hospitalized patients, 1090 patients with complete data were analyzed. Mean age was 40.5 ± 17.2 years, 66.7% were female. 32.0% of patients had previously engaged in SRB, in 76.3% intention was suicidal. 64.7% of patients had a pre-existing psychiatric disorder (PD). Patients with a pre-existing PD more often displayed prior SRB than those without PD (40.7% vs 15.3%; p

Abstract Cerebral amyloid angiopathy (CAA) is an age-related condition and a major cause of intracerebral hemorrhage and cognitive decline that shows close links with Alzheimer's disease (AD). CAA is characterized by the aggregation of amyloid-β (Aβ) peptides and formation of Aβ deposits in the brain vasculature resulting in a disruption of the angioarchitecture. Capillaries are a critical site of Aβ pathology in CAA type 1 and become dysfunctional during disease progression. Here, applying an advanced protocol for the isolation of parenchymal microvessels from post-mortem brain tissue combined with liquid chromatography tandem mass spectrometry (LC–MS/MS), we determined the proteomes of CAA type 1 cases (n = 12) including a patient with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), and of AD cases without microvascular amyloid pathology (n = 13) in comparison to neurologically healthy controls (n = 12). ELISA measurements revealed microvascular Aβ1-40 levels to be exclusively enriched in CAA samples (mean: > 3000-fold compared to controls). The proteomic profile of CAA type 1 was characterized by massive enrichment of multiple predominantly secreted proteins and showed significant overlap with the recently reported brain microvascular proteome of patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebral small vessel disease (SVD) characterized by the aggregation of the Notch3 extracellular domain. We found this overlap to be largely attributable to the accumulation of high-temperature requirement protein A1 (HTRA1), a serine protease with an established role in the brain vasculature, and several of its substrates. Notably, this signature was not present in AD cases. We further show that HTRA1 co-localizes with Aβ deposits in brain capillaries from CAA type 1 patients indicating a pathologic recruitment process. Together, these findings suggest a central role of HTRA1-dependent protein homeostasis in the CAA microvasculature and a molecular connection between multiple types of brain microvascular disease.

Abstract Background Although the total number of suicides decreased since the beginning of the 1980s, the number of suicide-related behaviors using self-intoxication increased. Therefore, research on the characteristics of individuals committing self-intoxication becomes of growing importance for risk assessments and the development of preventive measures. Methods In this prospective, observational, monocentric cohort study, all incoming calls at our Poisons Control Centre reporting suicide-related behaviors through self-intoxication, were analyzed via a standardized questionnaire over 12 months. Both univariate and bivariate analyses were performed. Results 1238 cases of deliberate intoxication were included in the study. The majority of cases occurred in the age group between 18 and 44 (n = 607/49%), two-thirds were female (n = 817/66%). The main substances used were antidepressants (n = 420/34%), peripheral analgesics (n = 322/26%) and neuroleptics (n = 282/23%). The majority of patients ingested substances from their prescribed medication (n = 640/82%) with the highest proportion in those aged over 64 years (n = 72/113; 91%, p

A 63-year-old male was admitted to a district hospital after ingesting ethanol and pirimiphos-methyl (PM) with suicidal intentions. History included alcoholic cirrhosis with alcoholism, adiposity, diabetes with cerebral microangiopathy, chronic renal insufficiency, heparin-induced thrombocytopenia, and status post necrotizing fasciitis. Emergency medical service reported an alert patient without signs of cholinergic crisis; activated charcoal and atropine were administered. Upon hospital arrival, he received fluid resuscitation, activated charcoal, and atropine. He was transferred to a toxicology unit the next day. On admission, he had no cholinergic signs (dry mucous membranes, warm skin, and mydriatic pupils) requiring small atropine doses (0.5 mg per hour). Four hours after admission, he developed bradycardia and respiratory distress, necessitating intubation. He received atropine by continuous infusion for 7 days (248 mg total) and obidoxime (bolus and continuous infusion). PM, pirimiphos-methyl-oxon (PMO), and phosphorylated tyrosine (Tyr) adducts derived from human serum albumin were analyzed in vivo. Cholinesterase status (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), inhibitory activity of patient plasma and reactivatability, and phosphorylated BChE-derived nonapeptides) was measured in vivo. Obidoxime and atropine were monitored. PM and PMO were detectable, PM with maximum concentration ∼24 h post admission (p.a.) and PMO at ∼18 h p.a. Tyr adducts were detectable. AChE in vivo was suppressed on admission, increased continuously after starting obidoxime, and reached maximum activity after ∼30 h. AChE in vivo and reactivatability remained at the same level until the end of monitoring. BChE was already suppressed on admission; termination of the antidote treatment was possible after BChE had recovered to 1/5th of its normal value and extubation was possible after BChE had recovered to 2/5th. While a substantial part of BChE was already aged on admission, aging continued peaking at ∼24 h p.a. After initiating obidoxime treatment, plasma levels increased until obidoxime plasma levels reached a steady state. On admission, plasma atropine level was low; it increased with the start of the continuous infusion. Afterward, the level dropped to a steady state. The clinical course was characterized by bouts of pneumonia, necessitating re-intubation and prolonged ventilation, sepsis, delirium, and a peripheral neuropathy. After psychiatric evaluation, the patient was discharged to a neurological rehabilitation facility after 77 days of hospital care.

Summary:. Harlequin ichthyosis (HI) is a rare congenital skin disorder caused by irregular epidermal differentiation. Syndactyly in HI is associated with thick hyperkeratotic skin flexion and angulation deformity of the hand and fingers resulting in limited function of the upper extremity. Traditional syndactyly release is limited as full-thickness skin grafts typically used in reconstruction are composed of diseased skin and require donor sites in a patient predisposed for adverse wound healing. This case report is a follow-up to a previous viewpoint written about digital escharotomies in a newborn with HI and outlines a second and fourth webspace syndactyly release with a dermal substitute. Despite early evidence of adequate release and improved hand function, recurrence of syndactyly was observed within 4 months of surgical release. Our experience described within this case report may suggest the limitations and possible alternatives of surgical release of syndactyly in the HI population.

Objective:. This study aimed to compare operative time, blood loss, and transfusion requirement in patients receiving a high tranexamic acid (TXA) dose of greater than 10 mg/kg versus those receiving a low dose of 10 mg/kg or less. Methods:. PubMed, Cochrane Central, and Embase were queried to perform a systematic review with meta-analysis. Studies reporting outcomes of TXA use in craniosynostosis surgery were included. TXA dosing, operative time, blood loss, and transfusion requirement were the primary outcomes studied. Other variables studied included age and types of craniosynostosis. Results:. In total, 398 individuals in the included articles received TXA for craniosynostosis surgery. TXA loading doses ranged from 10 mg/kg to 50 mg/kg. Overall, administration of TXA was not associated with changes in operative time, but was associated with decreased blood loss and transfusion requirement on meta-analysis. Comparison of high dose TXA (>10 mg/kg) versus low dose (10 mg/kg or less) showed no statistical differences in changes in operative time, blood loss, or transfusion requirement. Conclusions:. Overall, TXA reduced blood loss and transfusion requirement in patients undergoing surgery for craniosynostosis. There was no difference in outcomes between high dose and low dose regimens amongst those receiving TXA. Low dose TXA appears adequate to achieve clinical efficacy with a low adverse event rate.

Silicon (Si) absorption is highly variable among different plant types; however, few studies have examined variations among different cultivars within a single species. In this study, 10 different tomato cultivars, including determinants and indeterminants as well as hybrids and heirlooms, were hydroponically grown in the presence or absence of Si to determine the absorption and distribution of the nutrients in roots, stems, petioles, and leaves. A total elemental analysis revealed that Si concentrations significantly increased with Si treatment, and that root concentrations were significantly higher than those in leaves. Although a few species showed differences in carbon, nitrogen, and calcium concentrations in roots and leaves with Si treatment, many of the macronutrients and micronutrients were unaffected. These data suggest that tomato plants absorb Si within the macronutrient range and restrict its movement from roots to shoots.

Viruses manipulate host cell pathways to support infection. Here the authors show that SARS-CoV-2 infection modulates cellular metabolism and limits autophagy, and identify druggable host pathways for virus inhibition.

Abstract Background Traumatic spinal cord injury (SCI) is also a combat-related injury that is increasing in modern warfare. The aim of this work is to inform medical experts regarding the different course of bladder cancer in able-bodied patients compared with SCI patients based on the latest medical scientific knowledge, and to present decision-making aids for the assessment of bladder cancer as a late sequela of traumatic SCI. Methods A study conducted between January 1998 and December 2019 in the BG Trauma Hospital Hamburg formed the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 40 out of 7396 treated outpatient and inpatient SCI patients. General patient information, latency period, age at initial diagnosis, type of bladder management and survival of SCI patients with bladder cancer were collected and analysed. T category, grading and tumour entity in these patients were compared with those in the general population. Relevant bladder cancer risk factors in SCI patients were analysed. Furthermore, relevant published literature was taken into consideration. Results Initial diagnosis of urinary bladder cancer in SCI patients occurs at a mean age of 56.4 years (SD ± 10.7 years), i.e., approximately 20 years earlier as compared with the general population. These bladder cancers are significantly more frequently muscle invasive (i.e., T category ≥ T2) and present a higher grade at initial diagnosis. Furthermore, SCI patients show a significantly higher proportion of the more aggressive squamous cell carcinoma than that of the general population in areas not endemic for the tropical disease schistosomiasis. Consequently, the survival time is extremely unfavourable. A very important finding, for practical reasons is that, in the Hamburg study as well as in the literature, urinary bladder cancer is more frequently observed after 10 years or more of SCI. Based on these findings, a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance. Conclusions The results showed that urinary bladder cancer in SCI patients differs considerably from that in able-bodied patients. The presented algorithm is an important aid in everyday clinical practice for assessing the correlation between SCI and bladder cancer.

Encontrar y reunir el trabajo de las mujeres “invisibles” para preservarlas es cada vez más desafiante. Aunque las colecciones de IAWA abarcan varios siglos, se centran en mujeres nacidas en los siglos XIX y XX, cuyo trabajo es en su mayoría predigital —hecho a mano— y, como artefactos únicos en su tipo, corren el riesgo de perderse fácilmente en la historia dejando sin rastro. A medida que el trabajo desaparece inevitablemente, la IAWA continúa la búsqueda urgente de mujeres cuyos nombres solo conocen sus familias y círculos personales; mujeres que esperan en la periferia ser descubiertas e incluidas.

Volker Krutsch,1 Stephan Grechenig,2 Oliver Loose,3 Leonard Achenbach,4 Johannes Zellner,2 Heiko Striegel,5 Volker Alt,2 Johannes Weber,2 Markus Braun,6 Stephan Gerling,7 Werner Krutsch2 1Department of Otorhinolaryngology, Head and Neck Surgery, Paracelsus Medical University, General Hospital Nuremberg, Nuremberg, Germany; 2Department of Trauma Surgery, University Medical Center Regensburg, Regensburg, Germany; 3Clinic of Pediatric Surgery, Olga Hospital, Clinic Stuttgart, Stuttgart, Germany; 4Department of Trauma Surgery, University Hospital Würzburg, Würzburg, Germany; 5Department of Sports Medicine, University Hospital Tuebingen, Tuebingen, Germany; 6Department of Sports Medicine, Clinic Westfalen, Dortmund, Germany; 7Department of Paediatric and Young Adult Medicine, Clinic St. Hedwig, Barmherzige Brüder Regensburg, Regensburg, GermanyCorrespondence: Werner KrutschDepartment of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg 93053, GermanyTel +49 941 9446805Email werner.krutsch@ukr.dePurpose: Injury data of professional soccer players obtained from media reports are frequently used in scientific research, but the accuracy of such data is still unclear.Patients and Methods: Injuries of professional soccer players of the German first and second league were documented by continuously screening media reports over one season (2015– 2016). After the season, the validity of media-reported injuries was anonymously analyzed by the team physicians of 8 different soccer clubs.Results: A total of 255 injuries of 240 players of 8 professional soccer teams had been published online, of which 146 were confirmed by the team doctors as correct, yielding a rate of 57.3% of confirmed media-reported injuries. In addition, 92 injuries without media registration were detected and added to the online statistics, resulting in 347 injuries and an overall weak validity of media-based data of 42.1%. Statistical analysis showed that the validity of media-reported injury data depended on both the individual soccer club and the body site affected by injury: publications on knee injuries (78.2%) had a higher validity than those on foot injuries (46.2%), and publications on severe injuries had a higher validity (joint dislocation: 100%; ligament rupture: 82.9%; fracture: 73.3%) than those on minor injuries. Publications on specific severe soccer injuries, such as anterior cruciate ligament (ACL) injuries, had a validity of 100%.Conclusion: Media-based injury data were only valid for a few severe injury types such as ACL injuries. In daily soccer routine and scientific research, media-based data should thus only be used in combination with specific criteria or verification processes.Keywords: professional football, injury, evidence, media-based, severe injury, ACL

Abstract Background Myeloid derived suppressor cells (MDSCs) present a significant obstacle to cancer immunotherapy because they dampen anti-tumor cytotoxic T cell responses. Previous groups, including our own, have reported on the myelo-depletive effects of certain chemotherapy agents. We have shown previously that decitabine increased tumor cell Class I and tumor antigen expression, increased ability of tumor cells to stimulate T lymphocytes, depleted tumor-induced MDSC in vivo and augmented immunotherapy of a murine mammary carcinoma. Results In this study, we expand upon this observation by testing a next-generation DNA methyltransferase inhibitor (DNMTi), guadecitabine, which has increased stability in the circulation. Using the 4 T1 murine mammary carcinoma model, in BALB/cJ female mice, we found that guadecitabine significantly reduces tumor burden in a T cell-dependent manner by preventing excessive myeloid proliferation and systemic accumulation of MDSC. The remaining MDSC were shifted to an antigen-presenting phenotype. Building upon our previous publication, we show that guadecitabine enhances the therapeutic effect of adoptively transferred antigen-experienced lymphocytes to diminish tumor growth and improve overall survival. We also show guadecitabine’s versatility with similar tumor reduction and augmentation of immunotherapy in the C57BL/6 J E0771 murine breast cancer model. Conclusions Guadecitabine depleted and altered MDSC, inhibited growth of two different murine mammary carcinomas in vivo, and augmented immunotherapeutic efficacy. Based on these findings, we believe the immune-modulatory effects of guadecitabine can help rescue anti-tumor immune response and contribute to the overall effectiveness of current cancer immunotherapies.

Blood coagulation: Protein changes in platelets linked to thrombosis People at high risk for thrombosis (formation of a blood clot inside a blood vessel) show alterations in their platelet protein content. Lena Hell, Maria Zellner, Ingrid Pabinger and colleagues at the Medical University of Vienna, Austria, analyzed proteins found in blood platelets from people who were tested positive for lupus anticoagulants (LAs), antibodies known to increase the risk of thrombosis. Many proteins involved in platelet activation and blood coagulation were found at significantly different levels in people with both LAs and a history of thrombosis compared to control groups. Among these proteins were enzymes that promote clot formation, and regulators of neutrophils, white blood cells involved in the coagulation process. The findings could aid in the search for alternatives to existing anticoagulant therapies.

[This corrects the article DOI: 10.1371/journal.pone.0251194.].

Prediction of clinical course of intoxication is essential for timely initiation of appropriate medical treatment in patients hospitalized due to suicidal self-poisoning. In this retrospective single-centre study in patients hospitalized due to suicidal poisoning in a specialized clinical toxicology unit, we aimed to identify predictive factors associated with severe or fatal course of self-poisoning. All patients underwent at least one psychiatric exploration during their inpatient stay. Severity of poisoning was assessed on admission and after 24 hours according to the Poison Severity Score index (PSS). Spearman's rank correlation coefficient was used to test the association of PSS with sociodemographic, anamnestic and (pre-)clinical parameters. Multivariable binomial logistic regression analysis was performed to determine predictive factors for severe and/or fatal self-poisoning. 1090 patients were included in the study. Median age was 39 years (range 13-91), 66.7% of patients were female. PSS was classified in the majority as "minor" (n = 558, 51.2%) or "moderate" (n = 264, 24.2%). 61 patients (5.6%) had PSS "severe"; 14 patients (1.3%) died. A higher severity of poisoning positively correlated with duration of inpatient therapy (p

IntroductionUpon completion of the workup for stroke, etiology cannot be identified in approximately one-third of the patients, with an embolic stroke of undetermined source (ESUS) accounting for around 50% of these cryptogenic etiologies. Whether management of complex long-term monitoring in order to detect suspected atrial fibrillation (AFib) could be initiated and managed through a neurologist is not sufficiently investigated.Patients and MethodsWe recruited all consecutive patients with ESUS who received implantation after neurological adjudication of Reveal LINQ® loop recorder between January 2016 and July 2020. We collected demographic, clinical, heart- and neuroimaging, laboratory, and electrocardiographic data assessed on prolonged baseline ECG monitoring, number of supraventricular (SVEs) and ventricular (VEs) extrasystolic complexes, and from preimplantation ECG–PQ interval. AFib detection was manually supervised and determined positive when the duration was over 120 s.ResultsWe followed a total of 131 patients for a median of 504 days. There were 45 (34%) manually verified AFib diagnoses. In univariate analysis, earlier implantation after ESUS was associated with AFib detection (13 vs. 31 days, p = 0.011). In multivariate analysis, increased rate of AFib was associated with a more prolonged PQ interval (per 50-ms increase) (HR 1.99, 95% CI 1.39–2.85) and number of SVEs (HR 1.29, 95% CI 1.05–1.57) measured on pre-implantation ECG.ConclusionWe observed similar predictors for Afib after ESUS, albeit with higher frequency than previously reported. This study suggests that the neurologist-led decision, management, and evaluation of ILR after ESUS is feasible.

The meniscus is composed of an avascular inner region and vascular outer region. The vascular region has been shown to contain a progenitor population with multilineage differentiation capacity. Strategies facilitating the isolation and propagation of these progenitors can be used to develop cell-based meniscal therapies. Differential adhesion to fibronectin has been used to isolate progenitor populations from cartilage, while low oxygen or physioxia (2% oxygen) enhances the meniscal phenotype. This study aimed to isolate progenitor populations from the avascular and vascular meniscus using differential fibronectin adherence and examine their clonogenicity and differentiation potential under hyperoxia (20% oxygen) and physioxia (2% oxygen). Human vascular and avascular meniscus cells were seeded onto fibronectin-coated dishes for a short period and monitored for colony formation under either hyperoxia or physioxia. Non-fibronectin adherent meniscus cells were also expanded under both oxygen tension. Individual fibronectin adherent colonies were isolated and further expanded, until approximately ten population doublings (passage 3), whereby they underwent chondrogenic, osteogenic, and adipogenic differentiation. Physioxia enhances clonogenicity of vascular and avascular meniscus cells on plastic or fibronectin-coated plates. Combined differential fibronectin adhesion and physioxia isolated a progenitor population from both meniscus regions with trilineage differentiation potential compared to equivalent hyperoxia progenitors. Physioxia isolated progenitors had a significantly enhanced meniscus matrix content without the presence of collagen X. These results demonstrate that combined physioxia and fibronectin adherence can isolate and propagate a meniscus progenitor population that can potentially be used to treat meniscal tears or defects.

Proteomics is an indispensable analytical technique to study the dynamic functioning of biological systems via different proteins and their proteoforms. In recent years, bottom-up shotgun has become more popular than gel-based top-down proteomics. The current study examined the qualitative and quantitative performance of these two fundamentally different methodologies by the parallel measurement of six technical and three biological replicates of the human prostate carcinoma cell line DU145 using its two most common standard techniques, label-free shotgun and two-dimensional differential gel electrophoresis (2D-DIGE). The analytical strengths and limitations were explored, finally focusing on the unbiased detection of proteoforms, exemplified by discovering a prostate cancer-related cleavage product of pyruvate kinase M2. Label-free shotgun proteomics quickly yields an annotated proteome but with reduced robustness, as determined by three times higher technical variation compared to 2D-DIGE. At a glance, only 2D-DIGE top-down analysis provided valuable, direct stoichiometric qualitative and quantitative information from proteins to their proteoforms, even with unexpected post-translational modifications, such as proteolytic cleavage and phosphorylation. However, the 2D-DIGE technology required almost 20 times as much time per protein/proteoform characterization with more manual work. Ultimately, this work should expose both techniques’ orthogonality with their different contents of data output to elucidate biological questions.

Understanding Food–Energy–Water (FEW) systems is crucial in order to plan for a resilient and sustainable future of interdependent urban–rural regions. While research tends to focus on urban transitions, the topic remains understudied relative to urban-rural regions. The often conflicting pressures in these regions (e.g., urbanization and growing crop production) may pose distinctive challenges where large urbanizations are adjacent to sparsely populated rural areas. These systems may further shift in response to local and global economic and demographic trends, as well as climate change. Identifying these complex system trajectories is critical for sustainability and resilience planning and policy, which requires the pooling of both urban and rural expertise across multiple disciplines and domains. We convened panels of subject matter experts within a participatory causal loop diagramming (CLD) approach. Our workshops were facilitated by our research team to collaboratively construct the web of connections among the elements in the urban–rural FEW system. The CLDs and the discussions around them allowed the group to identify potentially significant lever points in the system (e.g., support for minority farmers to enhance food security while reducing waste), barriers to sustainability (e.g., laws restricting the sale of water treatment biosolids), and potential synergies across sectors (e.g., food and green energy advocacy jointly pressing for policy changes). Despite the greater understanding of urban–rural interdependence afforded by participatory CLD, urban factors were consistently prioritized in the representation of the integrated system, highlighting the need for new paradigms to support sustainable urban–rural transitions.

Background: The fatal consequences of an infection with severe acute respiratory syndrome coronavirus 2 are not only caused by severe pneumonia, but also by thrombosis. Platelets are important regulators of thrombosis, but their involvement in the pathogenesis of COVID-19 is largely unknown. The aim of this study was to determine their functional and biochemical profile in patients with COVID-19 in dependence of mortality within 5-days after hospitalization.Methods: The COVID-19-related platelet phenotype was examined by analyzing their basal activation state via integrin αIIbβ3 activation using flow cytometry and the proteome by unbiased two-dimensional differential in-gel fluorescence electrophoresis. In total we monitored 98 surviving and 12 non-surviving COVID-19 patients over 5 days of hospital stay and compared them to healthy controls (n = 12).Results: Over the observation period the level of basal αIIbβ3 activation on platelets from non-surviving COVID-19 patients decreased compared to survivors. In line with this finding, proteomic analysis revealed a decrease in the total amount of integrin αIIb (ITGA2B), a subunit of αIIbβ3, in COVID-19 patients compared to healthy controls; the decline was even more pronounced for the non-survivors. Consumption of the fibrin-stabilizing factor coagulation factor XIIIA (F13A1) was higher in platelets from COVID-19 patients and tended to be higher in non-survivors; plasma concentrations of the latter also differed significantly. Depending on COVID-19 disease status and mortality, increased amounts of annexin A5 (ANXA5), eukaryotic initiation factor 4A-I (EIF4A1), and transaldolase (TALDO1) were found in the platelet proteome and also correlated with the nasopharyngeal viral load. Dysregulation of these proteins may play a role for virus replication. ANXA5 has also been identified as an autoantigen of the antiphospholipid syndrome, which is common in COVID-19 patients. Finally, the levels of two different protein disulfide isomerases, P4HB and PDIA6, which support thrombosis, were increased in the platelets of COVID-19 patients.Conclusion: Platelets from COVID-19 patients showed significant changes in the activation phenotype, in the processing of the final coagulation factor F13A1 and the phospholipid-binding protein ANXA5 compared to healthy subjects. Additionally, these results demonstrate specific alterations in platelets during COVID-19, which are significantly linked to fatal outcome.

The hydrological drought in Northern Italy in 2022 was, in large part, the consequence of a snow drought in the Italian Alps in the winter of 2021/22 and the resulting deficit of melt water runoff. In this communication, we assessed the snow-cover dynamics in nine Alpine Italian catchments using long time series of satellite-derived snow line elevation (SLE) measurements. We compared the SLE of the hydrological year 2021/22 to the long-term dynamics of 1985–2021. In early 2022, the SLE was located several hundred meters above the expected median values in all of the nine catchments. This resulted in deficits of snow-covered area of up to 83% in the Western Alps (catchment of Sesia, March 2022) and up to 61% in the Eastern Alps (Brenta, March 2022) compared to the long-term median. Although snow-cover data from optical satellite imagery do not contain information about snow depth and water content, in a preliminary qualitative analysis, the derived SLE dynamics show good agreement with the Standardized Snowpack Index (SSPI) which is based on the snow water equivalent (SWE). While the exact relationships between SLE, SWE, and runoff have to be explored further on the catchment basis, long-time series of SLE may have potential for use in drought early warning systems.

Here, Gassen et al. show that S-phase kinase-associated protein 2 (SKP2) is responsible for lysine-48-linked poly-ubiquitination of beclin 1, resulting in its proteasomal degradation, and that inhibition of SKP2 enhances autophagy and reduces replication of MERS coronavirus.

Early osteoarthritis (OA), characterised by cartilage defects, is a degenerative disease that greatly affects the adult population. Cell-based tissue engineering methods are being explored as a solution for the treatment of these chondral defects. Chondrocytes are already in clinical use but other cell types with chondrogenic properties, such as mesenchymal stem cells (MSCs), are being researched. However, present methods for differentiating these cells into stable articular-cartilage chondrocytes that contribute to joint regeneration are not effective, despite extensive investigation. Environmental stimuli, such as mechanical forces, influence chondrogenic response and are beneficial with respect to matrix formation. In vivo, the cartilage is subjected to multiaxial loading involving compressive, tensile, shear and fluid flow and cellular response. Tissue formation mechanobiology is being intensively studied in the cartilage tissue-engineering research field. The study of the effects of hydrostatic pressure on cartilage formation belongs to the large area of mechanobiology. During cartilage loading, interstitial fluid is pressurised and the surrounding matrix delays pressure loss by reducing fluid flow rate from pressurised regions. This fluid pressurisation is known as hydrostatic pressure, where a uniform stress around the cell occurs without cellular deformation. In vitro studies, examining chondrocytes under hydrostatic pressure, have described its anabolic effect and similar studies have evaluated the effect of hydrostatic pressure on MSC chondrogenesis. The present review summarises the results of these studies and discusses the mechanisms through which hydrostatic pressure exerts its effects.

Abstract Background Suture materials and techniques are frequently evaluated in ex vivo studies by comparing tensile strengths. However, the direct measurement techniques to obtain the tensile forces in canine skin are not available, and, therefore, the conditions suture lines undergo is unknown. A soft elastomeric capacitor is used to monitor deformation in the skin over time by sensing strain. This sensor was applied to a sample of canine skin to evaluate its capacity to sense strain in the sample while loaded in a dynamic material testing machine. The measured strain of the sensor was compared with the strain measured by the dynamic testing machine. The sample of skin was evaluated with and without the sensor adhered. Results In this study, the soft elastomeric capacitor was able to measure strain and a correlation was made to stress using a modified Kelvin-Voigt model for the canine skin sample. The sensor significantly increases the stiffness of canine skin when applied which required the derivation of mechanical models for interpretation of the results. Conclusions Flexible sensors can be applied to canine skin to investigate the inherent biomechanical properties. These sensors need to be lightweight and highly elastic to avoid interference with the stress across a suture line. The sensor studied here serves as a prototype for future sensor development and has demonstrated that a lightweight highly elastic sensor is needed to decrease the effect on the sensor/skin construct. Further studies are required for biomechanical characterization of canine skin.

Summary: The ascorbate peroxidase APEX2 is commonly used to study the neighborhood of a protein of interest by proximity-dependent biotinylation. Here, we describe a protocol for sample processing compatible with immunoblotting and mass spectrometry, suitable to specifically map the content of autophagosomes and potentially other short-lived endomembrane transport vesicles without the need of subcellular fractionation. By combining live-cell biotinylation with proteinase K digestion of cell homogenates, proteins enriched in membrane-protected compartments can be readily enriched and identified.For complete details on the use and execution of this protocol, please refer to Zellner et al. (2021).

Proton radiography’s utilization of positively charged probing particles makes it susceptible to potential influences from electromagnetic forces generated at the target object. In this work, we investigate how the 800 MeV proton radiography system of Los Alamos National Laboratory would respond to such influences with intentions to develop proton radiography/deflectometry diagnostics capable of probing electromagnetic fields inside dynamically changing objects. To understand how the proton radiography system responds to object-generated electromagnetic fields, a series of simulations were performed, which map proton trajectories through the system. This leads to an understanding of how the radiographic images, normally dominated by multiple Coulomb scattering, would be modified. The simulations also highlight novel ways in which additional data could be collected to glean more information about electromagnetic influences within and around the target object.

This paper's top-level goal is to provide an overview of research conducted in the many academic domains concerned with forecasting. By providing a summary encompassing these domains, this survey connects them, establishing a common ground for future discussions. To this end, we survey literature on human judgement and quantitative forecasting as well as hybrid methods that involve both humans and algorithmic approaches. The survey starts with key search terms that identified more than 280 publications in the fields of computer science, operations research, risk analysis, decision science, psychology and forecasting. Results show an almost 10-fold increase in the application-focused forecasting literature between the 1990s and the current decade, with a clear rise of quantitative, data-driven forecasting models. Comparative studies of quantitative methods and human judgement show that (1) neither method is universally superior, and (2) the better method varies as a function of factors such as availability, quality, extent and format of data, suggesting that (3) the two approaches can complement each other to yield more accurate and resilient models. We also identify four research thrusts in the human/machine-forecasting literature: (i) the choice of the appropriate quantitative model, (ii) the nature of the interaction between quantitative models and human judgement, (iii) the training and incentivization of human forecasters, and (iv) the combination of multiple forecasts (both algorithmic and human) into one. This review surveys current research in all four areas and argues that future research in the field of human/machine forecasting needs to consider all of them when investigating predictive performance. We also address some of the ethical dilemmas that might arise due to the combination of quantitative models with human judgement.

IntroductionDue to aging and health status people may be subjected to a decrease of cognitive ability and subsequently also a decline of driving safety. On the other hand there is a lack of valid and economically applicable instruments to assess driving performance.ObjectiveThe study is designed to develop a valid screening-tool for fitness-to-drive assessment in older people with cognitive impairment externally validated on the basis of on-road driving performance.MethodsIn a single-centre, non-randomized cross-sectional trial cognitive functioning and on-road-driving-behavior of older drivers will be assessed. Forty participants with cognitive impairment of different etiology and 40 healthy controls will undergo an extensive neuropsychological assessment. Additionally, an on-road driving assessment for external validation of fitness to drive will be carried out. Primary outcome measures will be performance in attention, executive functions and visuospatial tasks that will be validated with respect to performance on the on-road-driving-test. Secondary outcome measures will be sociodemographic, clinical- and driving characteristics to systematically examine their influence on the prediction of driving behavior.DiscussionIn clinical practice counselling patients with respect to driving safety is of great relevance. Thus, having valid, reliable, time economical and easily interpretable screening-tools on hand to counsel patients is of great relevance for practitioners.Ethics and disseminationEthics approval was obtained from the Ethics Committee at the Ludwig-Maximilians-University Munich. The trial results will be disseminated through peer-reviewed publications and various conferences.Trial registration18-640. Trial registration: German Clinical Trials Register. Registration number: DRKS00023549.

Computational reproducibility is a corner stone for sound and credible research. Especially in complex statistical analyses-such as the analysis of longitudinal data-reproducing results is far from simple, especially if no source code is available. In this work we aimed to reproduce analyses of longitudinal data of 11 articles published in PLOS ONE. Inclusion criteria were the availability of data and author consent. We investigated the types of methods and software used and whether we were able to reproduce the data analysis using open source software. Most articles provided overview tables and simple visualisations. Generalised Estimating Equations (GEEs) were the most popular statistical models among the selected articles. Only one article used open source software and only one published part of the analysis code. Replication was difficult in most cases and required reverse engineering of results or contacting the authors. For three articles we were not able to reproduce the results, for another two only parts of them. For all but two articles we had to contact the authors to be able to reproduce the results. Our main learning is that reproducing papers is difficult if no code is supplied and leads to a high burden for those conducting the reproductions. Open data policies in journals are good, but to truly boost reproducibility we suggest adding open code policies.