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Downstream processing in the biomanufacturing industry has been under relentless pressure for several decades. The source of this pressure is the much greater scalability of upstream production, which can be [...]

In our final text on this year's Ostrava Days, Kurt Gottschalk, a journalist and radio DJ based in New York, presents his perspective on some of the pieces at this [...]

The taxpayer in Allen, TO. Memo. 2023-86, claimed bad debt deductions of over $17 million with respect to advances between companies the taxpayer controlled. The IRS denied the bad debt [...]

Serial cardiovascular magnetic resonance evaluation of children and young adults with SCD who underwent hematopoietic cell transplantation showed mean ECV, representing diffuse myocardial fibrosis, decreased 3.4% from baseline to 12 months posttransplantation. This trial was registered at www.clinicaltrials.govas #NCT04362293.

Of 182 positive blood cultures from neonates where both aerobic and anaerobic culture bottles were obtained, 18% recovered the pathogen exclusively in the anaerobic bottle. When both bottles recovered the pathogen, 67% were recovered earlier in the anaerobic bottle.

Camera traps are a powerful tool to monitor the activity pattern of species over long time periods. Camera data can be used to analyze activity patterns of or temporal niche partitioning among species. Temporal niche partitioning plays an important role for species coexistence and is under constant evolutionary pressure from predator-prey relationships. Our study aimed to investigate temporal shifts in activity patterns of red squirrels and two mammalian predators, red fox and marten (Martes spec.). Previous studies yielded different activity patterns for these species depending on location, season, predator-prey interactions, and food- availability. We used camera traps to monitor the activity of squirrels, red fox and martens throughout a whole year in a mountainous forest in southwestern Germany. We also investigated a possible difference in activity among different color morphs as coloration in mammals is often associated with concealment, for squirrels, however, such an effect could not be demonstrated so far. We found a diurnal activity for squirrels in all seasons with a bimodal activity pattern during spring, trimodal in summer and unimodal in fall and winter. Activity patterns did not differ between black and red color morphs. The activity of the squirrels showed only low to moderate overlaps with fox and marten, but there was still slight variation among seasons. Activity overlaps were higher in spring and summer, which coincides with breeding season. Our results suggest that predators might adjust their activity during squirrel breeding season to increase the chance of preying on their offspring. Squirrels in turn could benefit by minimizing the activity overlap during wintertime when they are highly visible to predators as trees are leaf-free or even snow might enhance the contrast between them and their background. Lastly, our results indicate that temporal niche portioning among red squirrel, red fox and martens might be rather fine scaled.

We propose a two-component data-driven controller to safely perform docking maneuvers for satellites. Reinforcement Learning is used to deduce an optimal control policy based on measurement data. To safeguard the learning phase, an additional feedback law is implemented in the control unit, which guarantees the evolution of the system within predefined performance bounds. We define safe and safety-critical areas to train the feedback controller based on actual measurements. To avoid chattering, a dwell-time activation scheme is implemented. We provide numerical evidence for the performance of the proposed controller for a satellite docking maneuver with collision avoidance.

I cannot say how many times, as an Officer and/or Administrator, an inmate told me--'I'm going to call the Ombudsman on this.' Truth be known, I had no idea who [...]

•Subsequent HCT can provide a benefit for a subset of patients who relapse post-HCT.•Disease status and interval between HCT episodes are associated with outcome.•Haploidentical donors are an acceptable option for second HCT.

The Antarctic Circumpolar Current (ACC) represents the world’s largest ocean-current system and affects global ocean circulation, climate and Antarctic ice-sheet stability1–3. Today, ACC dynamics are controlled by atmospheric forcing, oceanic density gradients and eddy activity4. Whereas palaeoceanographic reconstructions exhibit regional heterogeneity in ACC position and strength over Pleistocene glacial–interglacial cycles5–8, the long-term evolution of the ACC is poorly known. Here we document changes in ACC strength from sediment cores in the Pacific Southern Ocean. We find no linear long-term trend in ACC flow since 5.3 million years ago (Ma), in contrast to global cooling9and increasing global ice volume10. Instead, we observe a reversal on a million-year timescale, from increasing ACC strength during Pliocene global cooling to a subsequent decrease with further Early Pleistocene cooling. This shift in the ACC regime coincided with a Southern Ocean reconfiguration that altered the sensitivity of the ACC to atmospheric and oceanic forcings11–13. We find ACC strength changes to be closely linked to 400,000-year eccentricity cycles, probably originating from modulation of precessional changes in the South Pacific jet stream linked to tropical Pacific temperature variability14. A persistent link between weaker ACC flow, equatorward-shifted opal deposition and reduced atmospheric CO2during glacial periods first emerged during the Mid-Pleistocene Transition (MPT). The strongest ACC flow occurred during warmer-than-present intervals of the Plio-Pleistocene, providing evidence of potentially increasing ACC flow with future climate warming.

•Correlative studies are important to improve pediatric CAR T cell treatments.•Active areas of research are reviewed from clinical trials and real-world studies.•Priorities for future research to improve patient outcomes are outlined.

The article discusses Stereophile's annual feature called "Records to Die For," which has been renamed "Records to Live For" due to the COVID-19 pandemic. The feature asks writers to name their favorite albums of all time, regardless of musical or sonic merit, as long as they hold special meaning for the writer. This year's feature includes works by various artists such as Jimmy Buffett, Andris Nelsons and the Boston Symphony Orchestra, André Previn, Kirsty MacColl, The Mountain Goats, Jimmie Lunceford, Cesaria Evora, En Attendant Ana, The Human League, Little Steven & The Disciples of Soul, and Todd Rundgren. Each writer shares their personal connection to the chosen albums and highlights their musical qualities. The text provides brief summaries of various music albums, highlighting the unique qualities and significance of each album, providing a glimpse into the artist's style and the impact of their work. [Extracted from the article]

A conventional baited trap to attract insects, commonly known as banana trap, has been used to survey the diversity of Drosophilidae, a bioindicator group for ecological studies. Standardizing protocols to capture species is important, yet determining the most effective protocol for specific groups remains a question. In this study, we compiled information on protocols used to capture drosophilids across different Brazilian biomes. Our dataset, compiled by searching papers published from 1982 to 2023, includes details on collection localities, phenological pattern, food habit, and effective capture protocols for each species or group of species. We expect that researchers who want to develop strategies to capture drosophilid species can use the dataset to optimize the protocol to collect a particular species, group, or genus.

Hintergrund: Im Rahmen der Pandemie des SARS-CoV-2-Virus erlangte das Patientenkollektiv der Schwangeren früh Aufmerksamkeit. Initial wurde angesichts sich früh abzeichnender Krankheitsfälle bei jüngeren Patienten mit einem erheblichen Aufkommen peripartal zu betreuender, COVID-19-positiver Schwangerer gerechnet. Ziel der Arbeit: Diese Arbeit vermittelt einen Einblick in die SARS-CoV-2-Infektionszahlen im Rahmen der geburtshilflichen Anästhesie zu Beginn der Pandemie sowie während der zweiten Infektionswelle in Deutschland. Methoden: Über das COALA-Register (COVID-19 related Obstetric Anaesthesia Longitudinal Assessment-Registry) wurden sowohl von März bis Mai 2020 als auch von Oktober 2020 bis Februar 2021 in Deutschland und der Schweiz wöchentlich prospektiv Daten zu Verdachts- und bestätigten SARS-CoV-2-Fällen bei Schwangeren zum Zeitpunkt der Geburt erhoben. Betrachtet wurden die Verteilung dieser auf die Anzahl der Geburten, Zentren und Erhebungswochen sowie mütterliche Charakteristika und Krankheitsverläufe. Ergebnisse: Neun Zentren haben im Verlauf 44 SARS-CoV-2-positive Schwangere zum Zeitpunkt der Geburt bei 7167 Geburten (0,6 %) gemeldet (3 Fälle auf 2270 Geburten (0,4 %) und 41 Fälle auf 4897 Geburten (0,8 %)). Berichtet wurden 2 schwere COVID-19-Verläufe (n= 1 mit Todesfolge nach ECMO, n= 1 mit ECMO überlebt). Bei 28 (68 %) Patientinnen verlief die Infektion asymptomatisch. Ein Neugeborenes wurde im Verlauf positiv auf SARS-CoV‑2 getestet. Schlussfolgerung: Mithilfe des Registers konnte das Auftreten von Fällen zu Beginn der Pandemie zeitnah eingeschätzt werden. Es traten sporadisch Verdachtsfälle bzw. bestätigte Fälle auf. Aufgrund fehlender flächendeckender Testung muss aber von einer Dunkelziffer asymptomatischer Fälle ausgegangen werden. Während der zweiten Infektionswelle wurden 68 % asymptomatische Fälle gemeldet. Jedoch kann es bei jungen, gesunden Patientinnen ohne das Vorliegen typischer Risikofaktoren zu schwerwiegenden Verläufen kommen.

Zusammenfassung: Hintergrund und Ziel: Frühe glaukomatöse Gesichtsfelddefekte können auch außerhalb der zentralen 30° auftreten, die bei der Glaukomdiagnostik üblicherweise untersucht werden. Ziel dieser Studie war die Evaluation der diagnostischen Sensitivität überschwelliger Reize bei Glaukompatienten vor der Entwicklung reproduzierbarer Gesichstfelddefekte in der standartisierten automatischen 30°-Weiß-auf-weiß-Perimetrie. Methode: Es wurden 352 Augen von 352 Patienten (Alter zwischen 35 und 69, Visus 0,8 und besser) aus dem Erlanger Glaukomregister in diese Studie eingeschlossen und in zwei Gruppen eingeteilt (normal/präperimetrisch). Bei allen Patienten wurde ein standardisiertes Glaukomscreening durchgeführt, inklusive einer statischen Perimetrie mit dem Octopus 500EZ (G1 Programm, alle 3 Phasen). Bei 95 Augen erfolgte zusätzlich eine Untersuchung mit einem 135-Punkte-Testmuster des Humphrey Field Analyzer 750i zur Erfassung peripherer Gesichtsfelddefekte. Sensitivität und Spezifität wurde für jeden einzelnen Punkt in Phase 3 des G1-Programms und im Humphrey-135-Punkte-Testmuster berechnet. Es erfolgte die Berechnung eines Scores und eine quadrantenspezifische Analyse. Ergebnisse: Bei 33 von 176 (18,8%) Augen mit präperimetrischem Glaukom zeigte sich ein Score von 3 oder höher in Phase 3 des G1-Programms (normal: 17 von 176; 9,7%). Die Testorte mit der höchsten Signifikanz fanden sich im nasal-oberen Quadranten, korrespodierend zu einem neuroretinalen Randsaumverlust hauptsächlich im inferotemporalen Sektor bei der frühen glaukomatösen Sehnervatrophie. Schlussfolgerungen: Positive Testergebnisse bei überschwelliger Stimulation der mittleren und äußeren Peripherie finden sich mit der doppelten Häufigkeit bei Patienten mit präperimetrischem Glaukom, v. a. im nasal-oberen Quadranten. Longitudinale Studien werden zeigen, ob solche Untersuchungen einen prädiktiven Wert für die perimetrische Manifestation der Erkrankung haben.

AimsThe impact of tobacco use on readmission and medical and surgical complications has been documented in hip and knee arthroplasty. However, there remains little information about the effect of smoking on the outcome after total shoulder arthroplasty (TSA). We hypothesized that active smokers are at an increased risk of poor medical and surgial outcomes after TSA.MethodsData for patients who underwent arthroplasty of the shoulder in the USA between January 2011 and December 2015 were obtained from the National Readmission Database, and 90-day readmissions and complications were documented using validated coding methods. Multivariate regression analysis was performed to quantify the risk of smoking on the outcome after TSA, while controlling for patient demographics, comorbidities, and hospital-level confounding factors.ResultsA total of 196,325 non-smokers (93.1%) and 14,461 smokers (6.9%) underwent TSA during the five-year study period. Smokers had significantly increased rates of 30- and 90-day readmission (p = 0.025 and 0.001, respectively), revision within 90 days (p < 0.001), infection (p < 0.001), wound complications (p < 0.001), and instability of the prosthesis (p < 0.001). They were also at significantly greater risk of suffering from pneumonia (p < 0.001), sepsis (p = 0.001), and myocardial infarction (p < 0.001), postoperatively.ConclusionSmokers have an increased risk of readmission and medical and surgical complications after TSA. These risks are similar to those found for smokers after hip and knee arthroplasty. Many surgeons choose to avoid these elective procedures in patients who smoke. The increased risks should be considered when counselling patients who smoke before undertaking TSA.

What is the difference between matter and anti-matter? A. I. Insight's winning solution on the Particle Physics Task for the 2004 KDD Cup demonstrates how an accurate predictive model can be formulated without knowledge of the content of the data. Information on the data was not available for the modeling, including a description on the outcome to be predicted. In other words, an 80 x 150,000 grid of numbers with the header "Particle Physics" was all that was given to the 500+ registrants of this competition. Key steps in creating the winning model were interactive analysis of the variables, detection of interactions, a powerful self-organizing neural network, and customization of the 4 different error criteria.

Hintergrund: Die Neuroosteoarthropathie des Fußes wird in ein aktives und ein inaktives Stadium unterteilt, was Einfluss auf die weitere Therapie hat. Hierfür kann der histopathologische Charcot-Score (HCS) verwendet werden, da er ein Maß für die Entzündungsaktivität auf Basis von Gewebeproben darstellt. Fragestellung: In der vorliegenden Arbeit soll geklärt werden, ob eine erfolgreiche knöcherne Heilung nach Arthrodese abhängig von der Entzündungsaktivität der Erkrankung ist. Material und Methode: Es unterzogen sichN= 80 Patienten einer Korrekturarthrodese des Mittel- (Gruppe 1) oder Rückfußes/OSG (Gruppe 2). Unterschieden wurde zwischen Patienten mit/ohne Diabetes mellitus sowie mit/ohne Schmerzempfinden. Intraoperativ wurden Proben zur Bestimmung des HCS entnommen. Die knöcherne Heilung der Arthrodesen wurde 12 Wochen postoperativ mittels Computertomographie überprüft. Ergebnisse: Es ergab sich eine indirekte, signifikante Korrelation zwischen knöcherner Konsolidierung und HCS. In Gruppe 2 bestand bei Patienten ohne Schmerzempfinden eine signifikant schlechtere knöcherne Heilung. Tendenziell schien der HCS bei Patienten ohne Diabetes/ohne Schmerzempfinden erhöht zu sein. Diskussion: Die vorliegende Studie bestätigt die Vermutung, dass Korrekturarthrodesen nur im inaktiven Stadium der Charcot-Erkrankung durchgeführt werden sollten. Hohe Aktivitätsniveaus behindern offensichtlich die knöcherne Heilung. Der HCS ist ein relevanter prognostischer Faktor für die Therapieplanung.

Wild-type murine models for aging research have lifespans of several years, which results in long experimental duration and late output. Here we explore the short-lived non-inbred Titan mouse (DU6) as a mouse model to test longevity interventions. We show that Titan mice exhibit increased frailty and senescence-associated beta-galactosidase activity at an early age. Dietary intervention attenuates the frailty progression of Titan mice. Additionally, cyclic administration of the senolytic drug Navitoclax at an early age increases the lifespan and reduces senescence-associated beta-galactosidase activity. Our data suggests that Titan mice can serve as a cost-effective and timely model for longevity interventions in mammals.

Signaling pathways that drive gene expression are typically depicted as having a dozen or so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic post-translational modifications (PTMs) orchestrate nearly every cellular function, and we lack technologies to find causal links between these vast biochemical pathways and genetic circuits at scale. Here we describe the high-throughput, functional assessment of phosphorylation sites through the development of PTM-centric base editing coupled to phenotypic screens, directed by temporally resolved phosphoproteomics. Using T cell activation as a model, we observe hundreds of unstudied phosphorylation sites that modulate NFAT transcriptional activity. We identify the phosphorylation-mediated nuclear localization of PHLPP1, which promotes NFAT but inhibits NFκB activity. We also find that specific phosphosite mutants can alter gene expression in subtle yet distinct patterns, demonstrating the potential for fine-tuning transcriptional responses. Overall, base editor screening of PTM sites provides a powerful platform to dissect PTM function within signaling pathways.

Das Reizdarmsyndrom (RDS) und die funktionelle Dyspepsie (Reizmagen) sind chronische Erkrankungen des Verdauungstrakts und eine diagnostische sowie therapeutische Herausforderung. Zur Diagnosestellung werden vor allem in Studien meist die Rom-IV-Kriterien herangezogen. Im klinischen Alltag haben sich die nach der deutschen S3-Leitlinie modifizierten Diagnosekriterien zumindest beim RDS als unkompliziertere Alternative bewährt. Für die Diagnosestellung sind eine gründliche Anamnese und Basisdiagnostik mit möglicher gezielterer Diagnostik zum Ausschluss organischer Erkrankungen unabdingbar. Die Klinik beider Störungen ist variabel, sodass anhand führender Symptomcluster eine Einteilung in Subtypen vorgenommen werden kann. Dies kann auch das weitere therapeutische Vorgehen erleichtern, das symptomorientiert und probatorisch erfolgt. Richtig eingesetzt können die medikamentösen und nichtmedikamentösen Therapieoptionen zur Symptomkontrolle und damit Verbesserung der Lebensqualität beitragen.

Recent advances in immunotherapy have affirmed the curative potential of T cell-based approaches for treating relapsed and refractory cancers. However, the therapeutic efficacy is limited in part owing to the ability of cancers to evade immunosurveillance and adapt to immunological pressure. In this Review, we provide a brief overview of cancer-mediated immunosuppressive mechanisms with a specific focus on the repression of the surveillance and effector function of T cells. We discuss CD8+T cell exhaustion and functional heterogeneity and describe strategies for targeting the molecular checkpoints that restrict T cell differentiation and effector function to bolster immunotherapeutic effects. We also delineate the emerging contributions of the tumor microenvironment to T cell metabolism and conclude by highlighting discovery-based approaches for developing future cellular therapies. Continued exploration of T cell biology and engineering hold great promise for advancing therapeutic interventions for cancer.

Clinical supervision is crucial for the professional learning and development of practitioners in many fields. While many have articulated what should happen in clinical supervision, and evaluative research has been undertaken, little is known about the details of what actually happens in clinical supervision. This study addresses this gap, focusing on how professionals (psychologists) work with knowledge while collaboratively working through complex problems of practice. Six psychologists (three pairs) participated, audio-recording five supervision sessions, and giving two interviews each. Transcripts were analysed to uncover what was discussed and how problems were approached. Four ways of working with knowledge (epistemic practices) were found: recontextualising practice knowledge, recontextualising theoretical knowledge, story-telling, and asking expansive questions. These highlight important features of professional supervision practice that have not previously been approached theoretically as epistemic practices.

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Munich, February 18, 1943. A stack of white leaflets falls from the banister of the second floor in the atrium of the university. Dozens swirl down onto the atrium floor. [...]

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Three Actinobacillus pleuropneumoniaeisolates from clinical cases of porcine pleuropneumonia were positive by capsular serovar 12–specific PCR assay, but not reactive to antiserum prepared against serovar 12 using the rapid slide agglutination (RSA) test. The isolates were positive for apxIICA, apxIIICA, apxIBD, apxIIIBD, and apxIVAin the PCR toxin gene assay, which is the profile seen in serovars 2, 4, 6, 8, and 15, and reacted with antisera against serovars 3, 6, 8, 15, and 17. Nucleotide sequence analysis revealed that genes involved in the biosynthesis of capsular polysaccharide of the 3 isolates were identical or nearly identical to those of serovar 12. However, genes involved in the biosynthesis of O-polysaccharide of the 3 isolates were highly similar to those of reference strains of serovars 3, 6, 8, 15, 17, and 19. In agreement with results from the RSA test, transmission electron microscopic analysis confirmed the absence of detectable capsular material in the 3 isolates. The existence of nonencapsulated A. pleuropneumoniaeserovar K12:O3 would hamper precise serodetection.

Deep neural networks (DNN) have made impressive progress in the interpretation of image data so that it is conceivable and to some degree realistic to use them in safety critical applications like automated driving. From an ethical standpoint, the AI algorithm should take into account the vulnerability of objects or subjects on the street that ranges from “not at all”, e.g. the road itself, to “high vulnerability” of pedestrians. One way to take this into account is to define the cost of confusion of one semantic category with another and use cost-based decision rules for the interpretation of probabilities, which are the output of DNNs. However, it is an open problem how to define the cost structure, who should be in charge to do that, and thereby define what AI-algorithms will actually “see”. As one possible answer, we follow a participatory approach and set up an online survey to ask the public to define the cost structure. We present the survey design and the data acquired along with an evaluation that also distinguishes between perspective (car passenger vs. external traffic participant) and gender. Using simulation based F-tests, we find highly significant differences between the groups. These differences have consequences on the reliable detection of pedestrians in a safety critical distance to the self-driving car. We discuss the ethical problems that are related to this approach and also discuss the problems emerging from human–machine interaction through the survey from a psychological point of view. Finally, we include comments from industry leaders in the field of AI safety on the applicability of survey based elements in the design of AI functionalities in automated driving.

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The working group, “Clinical Tissue Regeneration” of the German Society of Orthopedics and Traumatology (DGOU) issues this paper to update their guidelines.Methods Peer-reviewed literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLTs) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available for a particular diagnostic or therapeutic concept, including the grade of recommendation. Besides the scientific evidence, all group members rated the statements to identify possible gaps between literature and current clinical practice.Conclusion In patients with minimal symptoms, OLT progression to ankle osteoarthritis is unlikely. Risk factors for progression are the depth of the lesion on MRI, subchondral cyst formation, and the extent of bone marrow edema. Conservative management is the adaptation of activities to the performance of the ankle joint. A follow-up imaging after 12 months helps not to miss any progression. It is impossible to estimate the probability of success of conservative management from initial symptoms and imaging. Cast immobilization is an option in OLTs in children, with a success rate of approximately 50%, although complete healing, estimated from imaging, is rare. In adults, improvement by conservative management ranges between 45% and 59%. Rest and restrictions for sports activities seem to be more successful than immobilization. Intra-articular injections of hyaluronic acid and platelet-rich plasma can improve pain and functional scores for more than 6 months. If 3 months of conservative management does not improve symptoms, surgery can be recommended.

This paper aims at establishing a dialogue between philosophy and psychology about the conditions and the process through which humans build epistemic relationships during ontogenetic development. By the latter term, we mean any form of interaction which is aimed at producing a belief about some relevant aspects of the world, present or absent, past or future and at assessing its degree of epistemic trustworthiness. The paper is built as a dialogue between a philosopher and a psychologist, who present different faces of the problem of epistemic legitimation respectively and discuss the possible ways in which the dialogue can lead to theoretical advancement in understanding the development of the human epistemic subject. The chapter is divided into four sections: in the first section, we outline how we develop ontogenetically as epistemic subjects, and the sense that our epistemic life depends on other people’s words or testimony; in the second section, we deal with the notion of epistemic injusticeand epistemic silencing; in the third section, we discuss strategies to counter epistemic silencing and; in the fourth part, we try to elaborate a synthesis and suggest a new beginning.

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This 2004 KDD Cup presents a perfect case where the usual neural network objective functions do not apply. While the contest problem consisted of 4 different entries with 4 different objective functions, this paper will focus on the solution optimizing GRMSE (Grouped Root Mean Squared Error). It will be shown that the more typical objective functions (including RMSE) cannot be as effective at meeting this criteria. While this objective function may be specific to this problem, and the reader may never see this exact function again in his/her lifetime, the idea behind this paper is applicable in many situations. Too often neural networks are used to minimize SSE (sum of the squares of the errors) or Cross Entropy, when the true measure of success for the model may require a small coding change to the Neural Network objective function. It is shown in this paper that a few small coding changes can make a big difference on a model's performance.

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