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As skaters, we love our dogs. Four wheels, four paws, howling with homies and driven to learn new tricks; open the door, get out of the house and explore. Not [...]

Josef Jatta returned to our table from a smoke break, grinning ear to ear. He had dipped outside to work up an appetite for our impending Czech feast and had [...]

'Please, don't do this!' Luke's exclamation echoed from the back row as Jerry carefully maneuvered the towering 84' tall Chevy passenger van into the downtown Toronto Whole Foods parking garage--despite [...]

First things first--where are you from? I'm from Costa Mesa, California. Would you consider yourself a Mesa park local? Yes, I grew up there and used to sleep in the [...]

Do you ever get to the airport well ahead of time and somehow still find yourself sprinting to the gate because it took 90 minutes for you and everyone else [...]

The functioning of a wide variety of charged macromolecules, from DNA to fuel cell membranes, is dependent on how the counterions surrounding them are arranged. In order to decrease Coulombic repulsion, some of the fixed charges on these molecules are neutralized by a fraction of the counterions─this phenomenon is called counterion condensation. The nature of counterion condensation can be only be inferred indirectly from traditional experiments such as X-ray scattering and modern experiments such as single molecule electrometry. The prevalent conclusion in the literature, based on both theory and experiment, is that the distribution of counterions is peaked right next to the macromolecule, i.e., condensation results in the formation of contact ion pairs. In this study, cryogenic electron microscopy (cryo-EM) was used to study the arrangement of condensed halide counterions near a positively charged polypeptoid nanofiber. The locations of both condensed and fixed charges were determined directly from atomic-scale images. Our experimentally determined counterion distributions were peaked at distances of about 5 Å away from the fixed positive charge, indicating the presence of a layer of water molecules between condensed ion pairs. We posit that this distribution is driven by the entropy of the condensed ions.

School teachers have demonstrated poor mental health and low levels of wellbeing, globally. Despite the high prevalence of depression, burnout, stress, and anxiety, few programs have been developed in collaboration with teachers that are appropriate for their needs and circumstances. The current mixed-methods study involved consultation with members of the teaching workforce in Australia to understand their preferences for a program to address their mental health and wellbeing. The sample included teachers and other key representatives from the education sector in New South Wales, Australia. There were 47 participants who completed online surveys, with a subset (n= 16) also attending two group workshops (n= 10 in the first workshop, n= 6 in the second workshop). Data were collected between May 2021 and October 2021. Descriptive statistics were calculated to summarise quantitative survey data, and thematic analysis was used to analyse qualitative data. Results from surveys and workshops found that a new approach is needed to address teacher mental health and wellbeing in schools. Participants expressed a preference for a strategy that combined a face-to-face approach with a digital component and focused on three areas: staff relationships, supportive leadership, and practical skill development. The results of this study provide guidance about areas to target to improve teacher mental health and wellbeing.

The need for sustainability is driving the transition from linear to circular production. Customers, driven by the desire for innovation, prefer new products with the latest cutting-edge functions and design. The problem is that used products from older product generations are hence less attractive, leading to a limited market for remanufactured products and generating less revenue than their new counterparts. Therefore, this research addresses the problem of reprocessing and technologically updating used products into the newest product generation. To address this problem of reprocessing and technological updating with a Circular Factory, the product’s function fulfillment must be predicted in different situations in a Circular Factory. Three key challenges in which the function fulfillment must be predicted are identified as: Analysis and Diagnostics of Used Products and Subsystems, Prediction for Pairing and Reprocess of the Embodimentand Design for Circular Factory. A model-based approach is presented to address these three key challenges by predicting product function fulfillment to enable cross-generational use of subsystems and components. Five different types of models are proposed: A Functional Model, a Reliability Modeland a Reference Architecture Modelat the high level of general product modeling, as well as a Digital Twinof an object instance and a Tolerance Schemeat the level of individual instances. A theoretical case study shows the possible application in a Circular Factory using the example of an angle grinder. However, it’s essential to acknowledge that substantial work is needed for the enhancement or development of these models before practical application. Successful application of these models allows the Circular Factory not only to maintain but also to increase the value of reprocessed products to enable offering on the primary market and contribute to the vision of realizing a perpetual innovative product.

Percutaneous active mechanical circulatory support (MCS) devices are being increasingly used in the treatment of acute myocardial infarction-related cardiogenic shock (AMICS) despite conflicting evidence regarding their effect on mortality. We aimed to ascertain the effect of early routine active percutaneous MCS versus control treatment on 6-month all-cause mortality in patients with AMICS.

It's been a while since the Emerica team hit the road together. Because of the pandemic, most of the riders have been confined to skating their local spots, predominantly around [...]

IMPORTANCE: Resuscitation with lower fractional inspired oxygen (FiO2) reduces mortality in term and near-term infants but the impact of this practice on very preterm infants is unclear. OBJECTIVE: To evaluate the relative effectiveness of initial FiO2 on reducing mortality, severe morbidities, and oxygen saturations (SpO2) in preterm infants born at less than 32 weeks’ gestation using network meta-analysis (NMA) of individual participant data (IPD). DATA SOURCES: MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and WHO ICTRP from 1980 to October 10, 2023. STUDY SELECTION: Eligible studies were randomized clinical trials enrolling infants born at less than 32 weeks’ gestation comparing at least 2 initial oxygen concentrations for delivery room resuscitation, defined as either low (≤0.3), intermediate (0.5-0.65), or high (≥0.90) FiO2. DATA EXTRACTION AND SYNTHESIS: Investigators from eligible studies were invited to provide IPD. Data were processed and checked for quality and integrity. One-stage contrast-based bayesian IPD-NMA was performed with noninformative priors and random effects and adjusted for key covariates. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality at hospital discharge. Secondary outcomes were morbidities of prematurity and SpO2 at 5 minutes. RESULTS: IPD were provided for 1055 infants from 12 of the 13 eligible studies (2005-2019). Resuscitation with high (≥0.90) initial FiO2 was associated with significantly reduced mortality compared to low (≤0.3) (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23-0.86; low certainty) and intermediate (0.5-0.65) FiO2 (OR, 0.34; 95% CrI, 0.11-0.99; very low certainty). High initial FiO2 had a 97% probability of ranking first to reduce mortality. The effects on other morbidities were inconclusive. CONCLUSIONS AND RELEVANCE: High initial FiO2 (≥0.90) may be associated with reduced mortality in preterm infants born at less than 32 weeks’ gestation compared to low initial FiO2 (low certainty). High initial FiO2 is possibly associated with reduced mortality compared to intermediate initial FiO2 (very low certainty) but more evidence is required.

Crumb rubber (CR) that had been used in an outdoor football stadium in the U.S.A. for over 10 years was sampled, analysed and compared to samples taken from an on-site, covered excess CR stockpile and from fresh CR that could be used to replace the used CR. These tests were accomplished to determine if the original CR properties had changed significantly, from new/un-used CR, which could have safety and performance implications if continued use of this CR was planned. A series of analytical and mechanical tests were performed to determine degradation effects over time that included Fourier-transform infrared spectroscopy (FTIR), solvent swell tests, differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), X-ray emission spectroscopy (XES), vertical impact, hardness and bulk density. Results inferred compositional differences and mechanical property changes between all three CR samples, with indications that the older CR was demonstrating concurrent increased crosslinking and molecular scissioning, with subsequent loss in resilience. The FTIR results indicated various polymer types present that originated from recycled automobile tyres as well as evidence of oxidation in the used CR. The DSC exhibited lower thermal enthalpy and higher glass transition temperatures confirming compositional changes in older samples. Both vertical impact and hardness tests showed a significant increase in hardness and lower resilience in the used CR. A significant decrease in average size in the used CR was revealed through sieving and microscopy, which indicated mechanical wear. Bulk density measurements of un-sieved used and stockpile CR showed a substantial increase in bulk density for the used samples. The fresh, new potential replacement CR appears to originate from a different supplier than the CR originally used on the sports surface (and accompanying stockpile CR) and possessed much higher resilience than the used CR.

Deferred (also known as delayed) cord clamping can improve survival of infants born preterm (before 37 weeks of gestation), but the optimal duration of deferral remains unclear. We conducted a systematic review and individual participant data network meta-analysis with the aim of comparing the effectiveness of umbilical cord clamping strategies with different timings of clamping or with cord milking for preterm infants.

Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth.

Accurate evaluation of the optic disc is a critical part of optometric practice. When a disc is not 'perfused, healthy, distinct and flat,' it can be difficult to differentiate between [...]

Die Zahl der innovationsorientierten Unternehmensgründungen in Deutschland ist in den letzten Jahren rückläufig. Eine häufige Ursache für das Scheitern von Gründungen ist, dass für die angebotenen Produkte und Dienstleistungen kein Marktbedarf besteht und diesem Thema zu wenig Aufmerksamkeit geschenkt wird. Marktrecherchen sind jedoch eine wichtige Voraussetzung für erfolgreiche Unternehmensgründungen. Daher wird ein Informationsrechercheleitfaden für Marktrecherchen vorgestellt, der ein methodisches und strukturiertes Vorgehen beinhaltet sowie die einzelnen Untersuchungsbereiche im Marktrechercheprozess aufzeigt. Der Informationsrechercheleitfaden basiert auf umfangreichen praktischen und theoretischen Erfahrungen aus dem Hochschul- und Beratungsumfeld. Er wird ergänzt durch eine Literatur- und Informationsressourcenrecherche in Universitätsbibliotheken im Silicon Valley, die ihre Studierenden im Hinblick auf Start-ups von Beginn des Studiums an in vielfältiger Weise erfolgreich unterstützen.

Shape adaption (SA) via piezo-ceramic actuation, and active flow control (AFC) by means of fluid injection and aspiration, are investigated within the Cluster of Excellence for Sustainable and Energy-Efficient Aviation (SE2A) with the goal of increasing the efficiency of multi-stage compressors—particularly at part-load, and of extending their operating range. Although both technologies have shown to be beneficial for the compressor off-design operation, drawbacks are still apparent at the aerodynamic design point when a single rotor or stator is equipped with SA or AFC, because of wake disturbances, which increase the incidence angle of the following row. Especially matching an improved component with its respective stage counterpart poses a major challenge in both research areas and is, therefore, addressed within this investigation. This work focuses on the first two stages of a high-pressure compressor, to compare and evaluate different combinations of shape adaption and active flow control. By considering structural requirements, such as a minimum blade thickness for the actuator application, and aerodynamic sensitivities, such as flow incidence and deviation due to off-design operation, a suitable configuration is derived and investigated in further detail.

AbstractLow serotonin is one factor implicated in the development of depression. 17β-estradiol (E2) has been shown to modulate gene expression regulating the neurotransmission of serotonin. Sex hormone levels fluctuate dramatically during the menopausal transition, coinciding with a 14-fold increased risk of depression. This review aimed to examine the effect of soy isoflavones to support decreased and variable E2 levels before and after menopause, linked to an investigation of the pathophysiological mechanisms underlying the protective influence of E2 on the serotonin pathway. The overall aim of this review is to assess the potential of soy isoflavones to reduce depression in middle-aged women. A systematic literature search was performed in three stages. 1,421 papers were screened for relevance to the research aims and objectives. 63 papers were selected based on pre-defined inclusion/exclusion criteria (13 reviews, 24 mechanistic and 26 intervention studies) and critically appraised. Available research supported the hypotheses that E2 increases serotonin synthesis and availability through stimulation of tryptophan hydroxylase-2 (TPH-2) and decreased degradation by monoamine oxidase-A (MAO-A). There was less scientific agreement on the effects of E2 on serotonin transporter (SERT) and serotonin receptors 1 A and 2 A. Studies varied widely on the effectiveness of soy isoflavones in reducing depressive symptoms in (peri)menopausal women. Animal and human studies acknowledge women’s increased risk of depression linked to fluctuating E2 rather than absolute levels. However, mechanisms linking E2 variability with depression remain an underrepresented area of research. Study limitations and heterogeneity may contribute to varying results for soy isoflavones and some effects of E2 on the serotonin pathway.

Because the eye is an extension of the brain, a neurologic examination can be a crucial diagnostic tool. The neuro exam allows you to assess structures neighboring those that are [...]

Many patients with moderately to severely active Crohn's disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn's disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study.

AbstractThis review aims to investigate the role of intestinal permeability (IP) in rheumatoid arthritis (RA), following the hypotheses that leakage of intestinal microbes can influence increased citrullination of peptides leading to anti-citrullinated protein antibody (ACPA) production and inflammation in RA; and that leaked microbes can migrate to the peripheral joints, leading to immune responses and synovitis in peripheral joints. This review explored the evidence for the link between microbial dysbiosis and increased IP in the inflammatory state in RA, as well as the role of increased citrullination and bacterial translocation in the link between microbiota and immune responses in RA. Furthermore, this research aims to evaluate the potential effect of probiotics on RA symptoms and pathogenesis viaproposed mechanisms, including the support of microbial balance and suppression of inflammatory factors in RA. A systematic literature search was conducted in three tranches (review, mechanism, intervention). 71 peer-reviewed papers met the inclusions criteria and are summarized in a narrative analysis. Primary studies were critically appraised, synthesized and their relevance to clinical practice evaluated. Evidence found in this mechanism review consistently supported intestinal dysbiosis and increased IP in arthritis. An altered intestinal microbiome was demonstrated in RA with specific microbes such as Collinsellaand Eggerthellacorrelating with increased IP, mucosal inflammation, and immune responses. Hypercitrullination and ACPA production correlated with arthritic symptoms and intestinal microbes were shown to influence hypercitrullination. Some in vitroand animal studies demonstrated a link between leakage of microbes and bacterial translocation, but further research is needed to elucidate the link between IP and citrullination. Probiotic intervention studies evidenced reductions in inflammatory markers IL-6 and TNFα, associated with proliferation of synovial tissue and pain perception in RA joint inflammation. Despite some conflict in the literature, probiotics may present a promising nutritional intervention in the suppression of both, disease activity and inflammatory markers.Key teaching pointsThere is evidence for a dysbiotic profile of the RA gut with specific RA-associated microbes.Increased intestinal permeability and leakage of PAD enzyme facilitates citrullination of peptides.Hypercitrullination and ACPA production correlate to arthritic signs.Microbial leakage and translocation plays a role in the pathogenesis of RA.Probiotics (e.g. L. Casei 01) may reduce inflammation and ameliorate RA symptoms.

Zusammenfassung: Zielsetzung: Die Expression von Urocortin (Ucn), ein aus 40 Aminosäuren bestehendes Neuropeptid, wurde im Prostatagewebe von Patienten mit BPH berichtet. In verschiedenen Organen ist Ucn bei der Regulation von lokalen Entzündungsreaktionen, Zellproliferation und Relaxation von glatter Muskulatur durch Aktivierung von „Corticotropin releasing factor rezeptor 2“ (CRFR2) beteiligt. Bisher wurde der CRFR2 in humaner Prostata noch nicht untersucht. Methodik: Die Expression von CRFR2 wurde im humanen Prostatagewebe (n=8) mittels RT-PCR und Immunhistochemie untersucht. Ergebnisse: In Prostatalysaten wurden spezifische Signale von CRFR2 mRNA nachgewiesen. Immunhistochemisch wurde CRFR2 im Zytoplasma der basalen, luminalen und zystisch veränderten Epithelzellen der Prostatadrüsen gefunden. Auch in Bereichen der glatten Muskulatur des Stromas und Endothelzellen der Gefäße zeigte sich eine intensive Färbung für CRFR2. Schlussfolgerungen: Unsere Untersuchung zeigte erstmalig die Expression von CRFR2 in humanem Prostatagewebe. Die pharmakologische Beeinflussung von CRFR2 könnte somit ein neuer Angriffspunkt bei der Therapie der klinischen BPH darstellen.

Abstract: Background: Laparoscopic inguinal hernia repair can be performed using light- or heavyweight meshes. Apart from the size of the mesh, its friction coefficient (μ0) and flexural stiffness are of crucial importance to avoidance of hernia recurrence. Methods: In the current biomechanical study, tensile tests were performed to determine the ultimate tensile strength and modulus of elasticity of six lightweight meshes and six heavyweight meshes for laparoscopic inguinal hernia repair. To determine their friction coefficient (μ0), the meshes were placed between a resected peritoneum and groin muscles during an autopsy. Meshes measuring 15 × 10 cm in size then were used in a hernia model with an opening size of 1.5, 3, or 5 cm. Results: The ultimate tensile strength and modulus of elasticity were significantly lower in the lightweight mesh group than in the heavyweight mesh group. The mean friction coefficient (μ0) of the meshes was 0.4. Given an opening of 1.5 cm, all meshes remained adequately stable. At opening sizes of 3 and 5 cm, the lightweight meshes flexed on the average by 3.16 ± 0.4 mm and 10.40 ± 2.5 mm, respectively. Heavyweight meshes, on the other hand, were significantly less flexible. Their mean flexure was, respectively, 0.34 ± 0.2 mm and 3.97 ± 0.7 mm (p < 0.001). Conclusion: Stable meshes are characterized by a small degree of flexure and do not slide into the gap even when subjected to repetitive loads. Therefore, in terms of hernia recurrence, meshes with greater flexural stiffness or well-fixed lightweight meshes that adequately overlap the hernia defect can be used for laparoscopic treatment of large inguinal hernias.

Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed.

Audrey Hepburn and the cast of the 1957 classic--and Bazaar-inspired--film Funny Face try on the season s striking new pieces Caption: 'Think pink!' THIS PAGE: On Kay Thompson: Jacket, blouse, [...]

ABSTRACTIntroductionThe mitogen-activated protein kinase (MAPK) family consist of p38 MAP kinases, c-Jun N-terminal kinases (JNKs) and extracellular signal-regulated kinases (ERKs). They are involved in a multitude of diseases, including inflammatory, autoimmune, neurodegenerative, and metabolic diseases as well as cancer. In recent years, further developments in the field of MAPK-inhibitors have been reported, including an isoform or downstream target selective inhibition of MAPKs as well as target protein degradation approaches.Areas coveredThis review summarizes newly patented MAPK-inhibitors that were claimed between 2018 and early 2023. Presented are the patents as well as their corresponding publications, the storyline of development, and clinical trials involving these compounds. This article elaborates a total of 27 patents, which were identified using established search engines.Expert opinionAlthough industrial research on MAPK-inhibitors has been ongoing for more than 20 years, novel clinical trials of MAPK-inhibitors as potential drug candidates are still being conducted in the period under review. Recently reported inhibitors show an excellent selectivity profile and are even achieving selectivity between closely related isoforms. This progression offers the possibility to eliminate unwanted side effects and may finally lead to the approval of the first MAPK-inhibitor.

We demonstrate colloidal, layer-by-layer growth of metal oxide shells on InP quantum dots (QDs) at room temperature. We show with computational modeling that native InP QD surface oxides give rise to nonradiative pathways due to the presence of surface-localized dark states near the band edges. Replacing surface indium with zinc to form a ZnO shell results in reduced nonradiative decay and a density of states at the valence band edge that resembles defect-free, stoichiometric InP. We then developed a synthetic strategy using stoichiometric amounts of common atomic layer deposition precursors in alternating cycles to achieve layer-by-layer growth. Metal-oxide-shelled InP QDs show bulk and local structural perturbations as determined by X-ray diffraction and extended X-ray absorption fine structure spectroscopy. Upon growing ZnSe shells of varying thickness on the oxide-shelled QDs, we observe increased photoluminescence (PL) quantum yields and narrowing of the emission linewidths that we attribute to decreased ion diffusion to the shell, as supported by phosphorus X-ray emission spectroscopy. These results present a versatile strategy to control QD interfaces for novel heterostructure design by leveraging surface oxides. This work also contributes to our understanding of the connections between structural complexity and PL properties in technologically relevant colloidal optoelectronic materials.

Biobanking is becoming increasingly important as a key tool for precision medicine, but neither biobanking nor precision medicine itself have generally been integrated in medical curricula. However, most medical students will encounter these topics in their future careers as physicians or researchers. The European Union (EU)-funded project eduBRoTHER aims to close this gap of professional input. Since the academic year 2020/21, students at the Faculty of Medicine of Pilsen—Charles University and the Faculty of Medicine of the University of Regensburg have been offered an innovative core elective subject that focuses on biobanking and precision medicine issues, using the concept of blended learning.

Early works1and recent advances in thin-film lithium niobate (LiNbO3) on insulator have enabled low-loss photonic integrated circuits2,3, modulators with improved half-wave voltage4,5, electro-optic frequency combs6and on-chip electro-optic devices, with applications ranging from microwave photonics to microwave-to-optical quantum interfaces7. Although recent advances have demonstrated tunable integrated lasers based on LiNbO3(refs. 8,9), the full potential of this platform to demonstrate frequency-agile, narrow-linewidth integrated lasers has not been achieved. Here we report such a laser with a fast tuning rate based on a hybrid silicon nitride (Si3N4)–LiNbO3photonic platform and demonstrate its use for coherent laser ranging. Our platform is based on heterogeneous integration of ultralow-loss Si3N4photonic integrated circuits with thin-film LiNbO3through direct bonding at the wafer level, in contrast to previously demonstrated chiplet-level integration10, featuring low propagation loss of 8.5 decibels per metre, enabling narrow-linewidth lasing (intrinsic linewidth of 3 kilohertz) by self-injection locking to a laser diode. The hybrid mode of the resonator allows electro-optic laser frequency tuning at a speed of 12 × 1015hertz per second with high linearity and low hysteresis while retaining the narrow linewidth. Using a hybrid integrated laser, we perform a proof-of-concept coherent optical ranging (FMCW LiDAR) experiment. Endowing Si3N4photonic integrated circuits with LiNbO3creates a platform that combines the individual advantages of thin-film LiNbO3with those of Si3N4, which show precise lithographic control, mature manufacturing and ultralow loss11,12.

Dieser Beitrag der Zeitschrift Gruppe. Interaktion. Organisation. (GIO) widmet sich der lernförderlichen Gestaltung eines roboterbasierten Assistenzsystems für industrielle Montagetätigkeiten. Individualisierte Produkte, kleinere Losgrößen und beschleunigte Prozesse sind Aspekte des digitalen Wandels in der industriellen Fertigung und Teil des Leitbilds einer flexiblen Produktion. Mensch-Roboter-Kollaboration und wissensbasiertes Engineering sind aktuelle Ansätze, um diesen Anforderungen gerecht zu werden. Dieser Artikel stellt an einem Anwendungsbeispiel (Verdrahtung von Schaltschränken) einen ersten Ansatz vor, wie mittels wissensbasierter Technologien (v. a. Ontologien und deren logische Interpretation) Vorschläge zur Arbeitszuteilung zwischen Menschen und Robotern sowohl nach ökonomischen als auch nach Kriterien der humanen Arbeitsgestaltung automatisiert erstellt werden können. Zum einen können für jede Aufgabe ihre Anforderungen mit den individuellen Fähigkeiten und Stärken der Beschäftigten sowie mit denen des kollaborativen Robotersystems in einem Mixed-Skill-Konzept nach betrieblichen Kennziffern (z. B. Zeit, Qualität) abgeglichen werden, um sich so einem optimalen Produktionsablauf anzunähern. Zum anderen können dabei Aspekte einer humanen Gestaltung der Mensch-Maschine-Interaktion (MMI) berücksichtigt werden, die vordringlich mit Blick auf Lernförderlichkeit zusammengeführt werden. Lernförderlichkeit in der MMI setzt Zeit, Handlungsräume und förderliche Inhalte voraus und ist zugleich eine zunehmende Notwendigkeit, um vorausschauend auf den dynamisierten Wandel von Arbeit zu reagieren. Denn gerade mit dem Technikeinsatz ist ein starker Tätigkeitswandel in Richtung Entscheidungsträger und Problemlöser verbunden, der neben Qualifizierung und Weiterbildung auch niedrigschwelliger, arbeitsintegrierter Lerngelegenheiten bedarf. Gerade die kollaborative Robotik als Schlüsseltechnologie der flexiblen Fertigung macht es nötig, neue Konzepte für die Organisation des hybriden Zusammenwirkens von Mensch und Roboter zu entwickeln. Im Folgenden wird aufbauend auf den grundlegenden Ansatz das Konzept eines technischen Demonstrators vorgestellt, welches entlang eines empirischen Fallbeispiels entwickelt wurde. Die prototypische, technische Umsetzung basiert auf einer Arbeitsumgebung mit einem Roboterarm und zugehörigen Werkzeugen, formalen semantischen Beschreibungen der Fähigkeiten und Tätigkeiten von Menschen und Robotern sowie einer intuitiven Benutzeroberfläche, unter anderem für die individuelle Anpassung der generierten Arbeitszuteilungen.

(Abstracted from Lancet2023;402:2209–2222)Deferring or delaying umbilical cord clamping for at least 60 seconds is an increasingly common practice for infants. For term neonates, this practice has been shown to improve hemoglobin and hematocrit levels and lower the risk of iron deficiency.

AbstractThe aim of this study was to develop a measure of quality for Single Expert Reports (known as child custody evaluations or CCEs in the United States) and assess their psychometric properties. The Quality Measure for Child Custody Evaluations (QM-CCE) was derived from a previous survey of judges, lawyers and psychologists that identified 30 key components of a CCE plus an item assessing Overall Quality. Forty-four students enrolled in Master of Psychology programs in New South Wales (N = 44), Australia read seven mock reports and rated the quality using the QM-CCE. Inter-rater reliability was within the acceptable to excellent range across reports (ICC = .79 − .95). Exploratory Factor Analysis found a single dimension that underpins the measure. Internal consistency of the sub-scales was excellent (α = .98). Inter-rater reliability was also excellent (ICC = .99). Although the single item, Overall Quality, was highly correlated with the Multi-item Response, systematic patterns of difference were found. Given the promising psychometric properties of the QM-CCE, it may be a useful instrument not only for research purposes but for evaluators to improve the quality of their work and for legal professionals to decide the weight accorded to the CCE.

ABSTRACTBackgroundInterleukin (IL)-36 signaling has been shown to be increased in ulcerative colitis (UC). Spesolimab, a novel humanized monoclonal antibody, targets the IL-36 pathway.Research Design and MethodsWe report safety, immunogenicity, and efficacy data of intravenous (IV) spesolimab in UC. Study 1: phase II, randomized, placebo-controlled trial (300 mg single dose; 450 mg every 4 weeks [q4w]; or 1,200 mg q4w, three doses). Study 2: phase IIa, randomized, placebo-controlled trial (1,200 mg q4w). Study 3: phase IIa, open-label, single-arm trial (1,200 mg q4w). Studies lasted 12 weeks, with a 12-, 24-, and 16-week safety follow-up, respectively.ResultsAdver+se event (AE) rates were similar for spesolimab and placebo in Studies 1 (N = 98; 64.9%; 65.2%) and 2 (N = 22; 86.7%; 71.4%); all patients in Study 3 (N = 8) experienced AEs. The most frequent investigator-assessed drug-related (spesolimab; placebo) AEs were skin rash (5.4%; 0%) and nasopharyngitis (4.1%; 0%) in Study 1; acne (13.3%; 0%) in Study 2; one patient reported skin rash, nasopharyngitis, headache, and acne in Study 3. Efficacy endpoints were not met.ConclusionsSpesolimab was generally well tolerated, with no unexpected safety concerns. The safety data are consistent with studies in other inflammatory diseases.

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophies and the most frequent cause of congenital blindness in children. To date, 25 genes have been implicated in the pathogenesis of this rare disorder. Performing an accurate molecular diagnosis is crucial as gene therapy is becoming available. This study aimed to report the molecular basis of Leber congenital amaurosis, especially novel and rare variants in 27 Polish families with a clinical diagnosis of LCA fully confirmed by molecular analyses. Whole exome sequencing or targeted next-generation sequencing (NGS) of inherited retinal dystrophies-associated (IRD) genes was applied to identify potentially pathogenic variants. Bidirectional Sanger sequencing and quantitative PCR (qPCR) were carried out for validation and segregation analysis of the variants identified within the families. We identified 28 potentially pathogenic variants, including 11 novel, in 8 LCA genes: CEP290, CRB1, GUCY2D, NMNAT1, RPGRIP1, CRX, LRAT1, and LCA5.This study expands the mutational spectrum of the LCA genes. Moreover, these results, together with the conclusions from our previous studies, allow us to point to the most frequently mutated genes and variants in the Polish cohort of LCA patients.

Acute pancreatitis is a major cause of hospital admissions in the United States, with the two primary causes being gallstones and alcohol.1The Atlanta classification system is an international classification on the severity of acute pancreatitis. In 2012, deficiencies and outdated nomenclature were removed to make a revised system that take into account advancements in research and clinical management. The revised Atlanta classification system (RACS) in 2012 standardized the nomenclature for acute pancreatitis and local complications to facilitate effective communication between clinicians and radiologists alike. Older terms such as pancreatic abscess, phlegmon, acute pseudocyst, and fluid collection are no longer used, as they are vague and can be misleading.

Zielsetzung: Die Konsensempfehlungen zur Begutachtung der Berufskrankheiten Nr. 2108 und Nr. 2110 (bandscheibenbedingte Erkrankungen der Lendenwirbelsäule) setzen bei der häufigsten Fallkonstellation, der sog. B2-Konstellation, voraus, dass mindestens eines von 3 Zusatzkriterien erfüllt ist. Zwei dieser Zusatzkriterien werden in der vorliegenden Sonderauswertung der Deutschen Wirbelsäulenstudie (DWS) empirisch überprüft. Methoden: Untersucht wurden die einwirkungsabhängigen Zusatzkriterien „besonders intensive Belastung“ (2. Zusatzkriterium) und „Belastungsspitzen“ (3. Zusatzkriterium). Mittels logistischer Regressionsanalyse wurden für Alter und Studienzentrum adjustierte Odds-Ratios (als Schätzer des relativen Bandscheiben-Erkrankungsrisikos) mit 95 %-Konfidenzintervallen (95 % KI) berechnet. Es wurden jeweils im gleichen Regressionsmodell Odds-Ratios für die Erfüllung und für die fehlende Erfüllung eines Zusatzkriteriums ermittelt. Grundsätzlich ist ein Kriterium dann zur Unterscheidung zwischen beruflich verursachten und nicht beruflich verursachten bandscheibenbedingten Erkrankungen geeignet, wenn die Risikoschätzer bei Erfüllung des jeweiligen Kriteriums deutlich höher liegen als bei fehlender Erfüllung des Kriteriums. Bei den Belastungsspitzen wurde die Höhe der mit Hebe- oder Tragevorgängen verbundenen Druckkräfte in der Lendenwirbelsäule (LWS) variiert, ab der das Kriterium der Belastungsspitzen als erfüllt angesehen wurde; ferner wurde die Zahl der Schichten variiert, in denen das Kriterium der Belastungsspitzen erfüllt sein musste. Alle Berechnungen wurden getrennt für Männer und Frauen für die Dosismodelle „Original-MDD“ und „BSG-Modell“ durchgeführt. Ergebnisse: Bei Vorliegen einer „besonders intensiven Belastung“ finden sich keine höheren bandscheibenbezogenen Erkrankungsrisiken als bei fehlendem Vorliegen dieses Zusatzkriteriums. Als „best estimate“ kann von der Erfüllung des Zusatzkriteriums „Belastungsspitzen“ dann ausgegangen werden, wenn beim BSG-Modell in mindestens 600 Schichten des gesamten Berufslebens Tagesdosen von mindestens 2,0 kNh (Kilonewton-Stunden = 1000 Newton-Stunden) pro Schicht bei Männern bzw. mindestens 0,5 kNh bei Frauen durch Belastungsspitzen (Druckkraft ≥ 6,0 kN bei Männern, ≥ 4,5 kN bei Frauen) erreicht werden. Schlussfolgerung: Die Sonderauswertung der Deutschen Wirbelsäulenstudie kann keine Bestätigung des 2. Zusatzkriteriums der B2-Konstellation „besonders intensive Belastung“ erbringen. Das 3. Zusatzkriterium „Belastungsspitzen“ wird hingegen grundsätzlich bestätigt – es sollte über mindestens 600 Arbeitsschichten erfüllt sein, um als Positivkriterium für die Anerkennung einer bandscheibenbedingten Berufskrankheit fungieren zu können.

Sustainability in product engineering is becoming increasingly relevant. Expanding stakeholder requirements for sustainable product engineering demand a more detailed and consistent understanding of the field to foster purposeful solutions. In this paper, a total of 174 publications in the field of product engineering were evaluated for their underlying understanding of sustainability based on a hermeneutic analysis. The results are threefold and include guiding questions for the analysis of publications in the field, a description of the current state of sustainability understanding in product engineering, and an explication framework for a proactive and targeted description of a sustainability understanding for use in future research and practice. These results are intended to contribute to establishing a more consistent and explicit understanding of sustainability in product engineering.

Hintergrund: In Anlehnung an den im deutschsprachigen Raum etablierten Veränderungsfragebogen des Erlebens und Verhaltens (VEV-R-2001), der für die direkte Veränderungsmessung eingesetzt wird, wurde ein neuer Fragebogen (VEV-KBT) entwickelt. Dieser ist auf die Zielbereiche der Konzentrativen Bewegungstherapie (KBT) ausgerichtet. Neben der Identifikation von änderungssensitiven Items wurden folgende Fragen untersucht: (a) Welche Dimensionen liegen den Items des VEV-KBT zugrunde? (b) In welchem Ausmaß erfahren ambulante Patienten nach 3 Monaten KBT Veränderungen der allgemeinen Stimmung und im Beschwerdeerleben im Vergleich zu Veränderungen in den KBT-bezogenen Zielbereichen? (c) Erleben Patienten nach 3‑monatiger ambulanter KBT ein anderes Ausmaß an Veränderungen als unbehandelte Personen innerhalb eines 3‑monatigen Zeitintervalls und als Patienten mit einer mindestens einjährigen KBT-Therapiedauer? (d) Geht eine Verbesserung in den KBT-bezogenen Zielbereichen mit einer Verbesserung der allgemeinen Stimmung und des Beschwerdeerlebens einher? Material und Methoden: Es wurden 3 Teilstichproben erhoben: 34 ambulante Patienten mit 3‑monatiger KBT-Behandlung, 94 ambulante Patienten mit einer mindestens einjährigen KBT-Behandlung und 93 unbehandelte Personen. Zur Beurteilung der subjektiven Beschwerden wurde eine Kurzform der Symptom-Checklist-90‑R verwendet, die aus 9 Items besteht. Die allgemeine Stimmung wurde mithilfe des VEV-R-2001 erfasst. Der VEV-KBT besteht aus 28 Items, die sich hauptsächlich auf das Erleben des eigenen Körpers und den Umgang mit dem eigenen Körper (im Kontakt mit anderen Menschen) beziehen. Ergebnisse: Als änderungssensitiv konnten 19 Items des VEV-KBT identifiziert werden. Diesen Items liegt ein dominanter Hauptfaktor zugrunde. Ambulante Patienten verzeichnen bereits nach 3 Monaten KBT eine signifikante Verbesserung hinsichtlich ihres Beschwerdeerlebens und ihrer allgemeinen Stimmung sowie in den KBT-bezogenen Zielbereichen. Es ist eine hohe Korrelation des VEV-R-2001 mit dem VEV-KBT zu verzeichnen. Beide Erhebungsinstrumente weisen vergleichbare Effektstärken auf. Schlussfolgerungen: Es gibt keine eindeutigen Hinweise darauf, dass die Differenzierung von KBT-bezogenen Zielbereichen in der direkten Veränderungsmessung eine besondere Relevanz hat. Dennoch stellt der VEV-KBT eine ökonomische Alternative zum VEV-R-2001 für die direkte Veränderungsmessung bei KBT-Behandlungen dar.

Spatially defined organoid damage enables the study of cellular repair processes. However, capturing dynamic events in living tissues is technically challenging. Here, we present a protocol for the application of single-cell damage in intestinal organoid models. We describe steps for isolating and cultivating murine colon organoids, lentivirus generation and transduction of organoids, single-cell ablation by a femtosecond laser, and follow-up imaging analysis. We provide examples for the image acquisition pipeline of dynamic processes in organoids using a confocal microscope.

In this study we investigate the effect of deep cryogenic treatment (DCT) on a high-alloyed ferrous alloy (HAFA) to understand the resulting chemical and physical changes to the HAFA's microstructure and properties. Using multiple materials analysis techniques, we uncover the fundamental chemical changes to the HAFA with DCT, and link changes in material properties to changes in the microstructure. The increased carbide nucleation with DCT is linked to greater solute mobility resulting from the modified stress state of the material and modified chemical bonding of the solutes with the matrix. In turn this provides the possibility of prior formation of nucleation points for primordial carbide formation that act as accelerators for both nucleation and evolution of carbides. These result in modified chemical and microstructural homogeneity of the material that fundamentally led to changes in the surface properties and applicability of HAFA in advanced wear, corrosion and fatigue resistance demanding conditions.

Patients experiencing functional constipation (FC) can participate in structured bowel management programs (BMPs) to manage constipation or fecal incontinence when standard management fails. We sought to evaluate the efficacy of BMPs for children with FC with and without neurodevelopmental disorders. We performed a retrospective review of children with FC who participated in our BMP from 2014 to 2021. Stool/urinary continence, bowel regimen, surgical history, parent-reported outcomes measures (PROMs: Cleveland Clinic Constipation Score, Baylor Continence Scale, Vancouver Symptom Score for Dysfunctional Elimination), and Pediatric Quality of Life Inventory (PedsQL) were assessed pre- and at least 9 months post-BMP. The cohort included 156 patients with a median age of 9 years and follow-up of 627 days (IQR: 389–808 days). Two sub-cohorts included patients with FC only (69%) and FC plus a neurodevelopmental disorder (31%): 59% attention-deficit/hyperactivity disorder, 33% autism spectrum disorder, and 8% obsessive-compulsive disorder. Both groups had significantly improved follow-up bowel movement frequency and continence (39%–90% neurodevelopmental, 44%–82% FC only, P< 0.001) and urinary continence (65%–90% neurodevelopmental, 69%–91% FC only, P< 0.02). There was a significant improvement in most of the PROMs at follow-up. Both groups experienced a clinically meaningful improvement in overall PedsQL scores (pre- and postBMP difference of >4.5). Patients with FC with and without a neurodevelopmental disorder had significant improvement in stool and urinary continence after undergoing a BMP. Further studies are needed to see if this improvement is durable over a longer period of time in this challenging cohort.