Squeezing is a nonclassical feature of quantum states that is a useful resource, for example, in quantum sensing of mechanical forces. Here, we show how to use optimal control theory to maximize squeezing in an optomechanical setup with two external drives and determine how fast the mechanical mode can be squeezed. For the autonomous drives considered here, we find the inverse cavity decay to lower-bound the protocol duration. At and above this limit, we identify a family of protocols leveraging a two-stage control strategy, where the mechanical mode is cooled before it is squeezed. Identification of the control strategy allows for two important insights: to determine the factors that limit squeezing and to simplify the time dependence of the external drives, making our protocol readily applicable in experiments.

Seit die Philosophie sich aus dem umfassenden Fundament der Metaphysik entlassen hatte, fächerte sie sich, ähnlich den Wissenschaften, in fachliche Segmente auf: Epistemologie, Ontologie, Geschichtsphilosophie, politische Philosophie, Naturphilosophie, Existenzphilosophie, praktische Philosophie, Ethik, Wissenschaftstheorie etc. Für das Wirtschaftliche im Philosophischen etablierte sich ab etwa Ende des 19. Jahrhunderts der Name ‘Wirtschaftsphilosophie’. Aus der Wirtschaftsphilosophie wurde aber bislang keine eigene philosophische Teildisziplin, vielmehr wurde sie auf unbestimmte Weise dem weiten Bereich der Praktischen Philosophie zugeschlagen. Wirtschaftsphilosophie ist aber vielmehr ein Reflexionsraum, der alle fachlich ausdifferenzierten Segmente des Philosophischen durchzieht. Das zeigt sich vor allem daran, auf welch verschiedene Art Wirtschaftsphilosophie heute betrieben wird: beispielsweise als epistemologische Befragung der vorherrschenden Semantik der Ökonomik, als Hinterfragen der Rationalitätsphilosophie der modern economics, als gabenökonomische Spurenanalyse einer Reziprozitätsphilosophie im Ökonomischen, als geschichtsphilosophische Rekonstruktion des Kapitalismus und seiner Industrialisierungswirkungen, als Rhetorik des Ökonomischen und ihrer narrativen Ausprägungen, als medienphilosophische Rekonstruktion der Finanzökonomie, als ethische Analyse von Normengeltung im Ökonomischen, als Philosophie der Dynamik der Ordnungsvorstellungen in der Geschichte, als politische Philosophie der politischen Ökonomie u.a. Es bildet sich kein Standardmodell heraus, sondern 2 ein bewegliches Feld philosophischer Reflektion des Ökonomischen, zum Teil “in rücksichtsloser Überschreitung” (Rorty) etablierter Begriffssysteme, um Neubeschreibungen und neue Interpretationen zu leisten. Die Philosophie hat immer schon das wirtschaftliche Handeln des Menschen thematisiert. Einschlägige Ansätze finden sich von Platon und Aristoteles über Thomas von Aquin, John Locke, Wolff, Rousseau, Fichte, Hegel, Marx und Nietzsche bis zu Bataille, Baudrillard, Derrida, Rawls, Sen und anderen. Diese Ansätze bildeten sich aber nicht zu einer spezifischen Wirtschaftsphilosophie aus, sondern blieben Reflexionen des Ökonomischen im Kontext der je eigenen Positionen und Ansätze. Heute zeigt sich: Die Philosophie, soweit sie das Wirtschaften reflektiert, denkt über die Wirtschaft als Sphäre nach, polyvalent, in all ihren Dimensionen, die das Effiziente weit übersteigen. Sie kann die Wirtschaft in ihrer Spannung zwischen Überfluss, Freiheit und Notwendigkeit reflektieren, ohne Dogmen, Mythen oder Ideologien aufzusitzen. Dieses intellektuelle Potenzial wird jedoch nicht genutzt, wenn man die Wirtschaftsphilosophie auf praktische Philosophie bzw. auf Wirtschaftsethik einschränkt. Angemessen wäre es heute, Wirtschaftsphilosophie als ein disziplinenübergreifendes Projekt anzusehen, innerhalb dessen die Reflexion erkenntnistheoretischer und methodologischer Aspekte und deren praktische Konsequenzen sowohl für die ökonomische Theoriebildung als auch das wirtschaftliche Handeln im Vordergrund stehen. Eine solche Ausfaltung des wirtschaftsphilosophischen Reflexionspotentials umfasst ein Spektrum von philosophischen Ansätzen über ökonomische Grundlagenfragen, Theorien und Praktiken, wodurch kein einheitliches Feld entsteht, sondern sich verschiedene Methoden, Narrationen, Systeme und Diskurse bilden. Ziel wirtschaftsphilosophischer Konsolidierung sollte es daher nicht sein, eine ähnliche fachliche Konsistenz wie die Wirtschaftswissenschaften erlangen zu wollen (ein Ideal, das derzeit auch innerhalb der Ökonomik herausgefordert wird), sondern einen Reflexionsraum zu schaffen, der die verschiedenen ökonomischen Theorien und Praktiken spiegeln kann (vor allem in Bezug auf ihre kontextuelle und kulturelle Einbettung). Vor diesem Hintergrund fasst das Positionspapier die wichtigsten Ergebnisse des Workshops zusammen, beschreibt die Potentiale und Probleme der Wirtschaftsphilosophie und macht Vorschläge für die Positionierung der Wirtschaftsphilosophie in Forschung, Lehre und Öffentlichkeit.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized systemic autoinflammatory disease caused by somatic mutations in hematopoietic progenitor cells. This case series of four patients with VEXAS syndrome and comorbid myelodysplastic syndrome (MDS) aims to describe clinical, imaging, and hematologic disease presentations as well as response to therapy. Four patients with VEXAS syndrome and MDS are described. A detailed analysis of imaging features, hemato-oncological presentation including bone marrow microscopy and clinical-rheumatological disease features and treatment outcomes is given. All patients were male; ages ranged between 64 and 81 years; all were diagnosed with MDS. CT imaging was available for three patients, all of whom exhibited pulmonary infiltrates of varying severity, resembling COVID-19 or hypersensitivity pneumonitis without traces of scarring. Bone marrow microscopy showed maturation-disordered erythropoiesis and pathognomonic vacuolation. Somatic mutation in the UBA1 codon 41 were found in all patients by next-generation sequencing. Therapy regimes included glucocorticoids, JAK1/2-inhibitors, nucleoside analogues, as well as IL-1 and IL-6 receptor antagonists. No fatalities occurred (observation period from symptom onset: 18-68 months). Given the potential underreporting of VEXAS syndrome, we highly recommend contemporary screening for UBA1 mutations in patients presenting with ambiguous signs of systemic autoinflammatory symptoms which persist over 18 months despite treatment. The emergence of cytopenia, especially macrocytic hyperchromic anemia, should prompt early testing for UBA1 mutations. Notably conspicuous, pulmonary alterations in CT imaging of patients with therapy-resistant systemic autoinflammatory symptoms should be discussed in interdisciplinary medical teams (Rheumatology, Hematology, Radiology and further specialist departments) to facilitate timely diagnosis during the clinical course of the disease.

Background Considering the expected increase in the elderly population and the growing emphasis on aging-related biomedical research, the demand for aged laboratory animals has surged, challenging established husbandry practices. Our objective was to establish a cost-effective method for environmental enrichment, utilizing the liver as a representative organ to assess potential metabolic changes in response to differing enrichment levels.

Methods We conducted a six-month study involving 24 male Sprague Dawley rats, randomly assigned to four environmental enrichment groups. Two groups were housed in standard cages, while the others were placed in modified rabbit cages. Half of the groups received weekly playtime in an activity focused rat housing unit. We evaluated hormone levels, playtime behavior, and subjective handling experience. Additionally, liver tissue proteomic analysis was performed.

Results Initial corticosterone levels and those after 3 and 6 months showed no significant differences. Yet, testosterone levels were lower in the control group by the end of the study (p = 0.007). We observed 1871 distinct proteins in liver tissue, with 77% being common across groups. In gene ontology analysis, no specific pathways were overexpressed. In semiquantitative analysis, we observed differences in proteins associated in lipid metabolism such as Apolipoprotein A-I and Acyl-CoA 6-desaturase, which were lower in the control group (p = 0.024 and p = 0.009). Rats in the intervention groups with weekly playtime displayed the least amount of reported distress during inspection or upon room entry and were less prone to accepting treats. Removing animals from their enclosure was most effortless for those in the large cage group. Over time, there was a decrease in conflicts among rats that interacted only twice weekly during playpen time.

Discussion In summary, refining husbandry practices for aging rats is both simple and budget-friendly, with no apparent adverse effects on stress levels, animal development, or relevant metabolic changes in the liver.

The aim of our study was to evaluate the potential role of Artificial Intelligence tools like ChatGPT in patient education. To do this, we assessed both the quality and readability of information provided by ChatGPT 3.5 and 4 in relation to Anterior Cruciate Ligament (ACL) injury and treatment. ChatGPT 3.5 and 4 were used to answer common patient queries relating to ACL injuries and treatment. The quality of the information was assessed using the DISCERN criteria. Readability was assessed with the use of seven readability formulae: the Flesch-Kincaid Reading Grade Level, the Flesch Reading Ease Score, the Raygor Estimate, the SMOG, the Fry, the FORCAST, and the Gunning Fog. The mean reading grade level (RGL) was compared with the recommended 8th-grade reading level, the mean RGL among adults in America. The perceived quality and mean RGL of answers given by both ChatGPT 3.5 and 4 was also compared. Both ChatGPT 3.5 and 4 yielded DISCERN scores suggesting "good" quality of information, with ChatGPT 4 slightly outperforming 3.5. However, readability levels for both versions significantly exceeded the average 8th-grade reading level for American patients. ChatGPT 3.5 had a mean RGL of 18.08, while the mean RGL of ChatGPT 4 was 17.9, exceeding the average American reading grade level by 10.08 grade levels and 9.09 grade levels, respectively. While ChatGPT can provide both reliable and good quality information on ACL injuries and treatment options, the readability of the content may limit its utility. Additionally, the consistent lack of source citation represents a significant area of concern for patients and clinicians alike. If AI is to play a role in patient education, it must reliably produce information which is accurate, easily comprehensible, and clearly sourced.

Although endangerment towards others is a criterion for an involuntary admission in many countries, research on risk assessment of endangerment among involuntarily admitted individuals is limited. In this retrospective case-control study, we calculated scores for a German-translated version of the Violence Risk Screening-10 (V-RISK-10) and the Broset Violence Checklist (BVC) in a sample of 111 people undergoing an involuntary admission in Reinickendorf, Berlin. Outcomes were violence, coercive measures, and readmission. In line with our hypotheses, the BVC demonstrated stronger predictive validities for short-term, and V-RISK-10 for long-term events. There was an incremental validity for both instruments for restraint 24 hours after admission and any violence until discharge. These findings support the evidence that structured risk assessment instruments may be useful for individuals undergoing an involuntary admission. Ethical considerations about screening procedures are discussed.

Fluorescently labelled compounds are often employed to study the paracellular properties of epithelia. For flux measurements, these compounds are added to the donor compartment and samples collected from the acceptor compartment at regular intervals. However, this method fails to detect rapid changes in permeability. For continuous transepithelial flux measurements in an Ussing chamber setting, a device was developed, consisting of a flow-through chamber with an attached LED, optical filter, and photodiode, all encased in a light-impermeable container. The photodiode output was amplified and recorded. Calibration with defined fluorescein concentration (range of 1 nM to 150 nM) resulted in a linear output. As proof of principle, flux measurements were performed on various cell lines. The results confirmed a linear dependence of the flux on the fluorescein concentration in the donor compartment. Flux depended on paracellular barrier function (expression of specific tight junction proteins, and EGTA application to induce barrier loss), whereas activation of transcellular chloride secretion had no effect on fluorescein flux. Manipulation of the lateral space by osmotic changes in the perfusion solution also affected transepithelial fluorescein flux. In summary, this device allows a continuous recording of transepithelial flux of fluorescent compounds in parallel with the electrical parameters recorded by the Ussing chamber.

Data are scarce on the role of pathogenic germline variants in BRCA1 and BRCA2 (gBRCAm) in subtype-specific survival in young women who develop breast cancer under the age of 40. This retrospective, real-world cohort study assessed the distant disease-free survival (DDFS) and overall survival (OS) of young women diagnosed with breast cancer between 2008 and 2019 while taking into consideration the interaction of clinical subtypes and the gBRCA status. Among 473 women, HR+/Her2- was the most common subtype (49.0%), followed by TNBC (31.3%), HR+/Her2+ (13.7%), and Her2+/HR- (5.9%). The gBRCA status was known for 319 cases (gBRCAwt (wild-type - without pathogenic variants in BRCA1 or BRCA2): 204, gBRCA1m: 83, gBRCA2m: 31, 1 patient with both). The distribution of clinical subtypes varied depending on the gBRCA status (p < 0.001). In survival analysis with a median follow-up of 43 months, the unadjusted DDFS and OS were worse for gBRCAwt TNBC compared to both HR+ subtypes, but not for gBRCAm TNBC patients. T-stage, nodal involvement, and the gBRCA status were identified as significant for survival in TNBC. In TNBC, gBRCAm was associated with better DDFS and OS than gBRCAwt (5-year DDFS 81.4% vs. 54.3%, p = 0.012 and 5-year OS 96.7% vs. 62.7%, p < 0.001). In contrast, in HR+/Her2- patients, gBRCAm patients showed a tendency for worse survival, though not statistically significant. Subtype-specific survival in young women with breast cancer needs to be evaluated in interaction with the gBRCA status. For TNBC, gBRCAm is of favorable prognostic value for overall survival, while patients with gBRCAwt TNBC need to be considered to have the highest risk for adverse survival outcomes.

Trustworthy medical AI requires transparency about the development and testing of underlying algorithms to identify biases and communicate potential risks of harm. Abundant guidance exists on how to achieve transparency for medical AI products, but it is unclear whether publicly available information adequately informs about their risks. To assess this, we retrieved public documentation on the 14 available CE-certified AI-based radiology products of the II b risk category in the EU from vendor websites, scientific publications, and the European EUDAMED database. Using a self-designed survey, we reported on their development, validation, ethical considerations, and deployment caveats, according to trustworthy AI guidelines. We scored each question with either 0, 0.5, or 1, to rate if the required information was "unavailable", "partially available," or "fully available." The transparency of each product was calculated relative to all 55 questions. Transparency scores ranged from 6.4% to 60.9%, with a median of 29.1%. Major transparency gaps included missing documentation on training data, ethical considerations, and limitations for deployment. Ethical aspects like consent, safety monitoring, and GDPR-compliance were rarely documented. Furthermore, deployment caveats for different demographics and medical settings were scarce. In conclusion, public documentation of authorized medical AI products in Europe lacks sufficient public transparency to inform about safety and risks. We call on lawmakers and regulators to establish legally mandated requirements for public and substantive transparency to fulfill the promise of trustworthy AI for health.

In childhood, retinoblastoma (RB) is the most common primary tumor in the eye. Long term therapeutic management with etoposide of this life-threatening condition may have diminishing effectiveness since RB cells can develop cytostatic resistance to this drug. To determine whether changes in receptor-mediated control of Ca2+ signaling are associated with resistance development, fluorescence calcium imaging, semi-quantitative RT-qPCR analyses, and trypan blue dye exclusion staining patterns are compared in WERI-ETOR (etoposide-insensitive) and WERI-Rb1 (etoposide-sensitive) cells. The cannabinoid receptor agonist 1 (CNR1) WIN55,212-2 (40 mu M), or the transient receptor potential melastatin 8 (TRPM8) agonist icilin (40 mu M) elicit similar large Ca2+ transients in both cell line types. On the other hand, NGF (100 ng/mL) induces larger rises in WERI-ETOR cells than in WERI-Rb1 cells, and its lethality is larger in WERI-Rb1 cells than in WERI-ETOR cells. NGF and WIN55,212-2 induced additive Ca2+ transients in both cell types. However, following pretreatment with both NGF and WIN55,212-2, TRPM8 gene expression declines and icilin-induced Ca2+ transients are completely blocked only in WERI-ETOR cells. Furthermore, CNR1 gene expression levels are larger in WERI-ETOR cells than those in WERI-Rb1 cells. Therefore, the development of etoposide insensitivity may be associated with rises in CNR1 gene expression, which in turn suppress TRPM8 gene expression through crosstalk.

We provide quantitative evidence on the relationship between military spending and innovation in the 19th century. Combining innovation data from world fairs and historical military data across Europe, we show that national military spending is associated with national innovation towards war logistics such as food processing, but less towards war technology such as guns. This innovation pattern reflects differences in the historical markets for war supplies: While the armed forces sourced weapons globally, the market for food remained local.

Background: Myasthenia gravis (MG) is a rare autoimmune disease characterized by fatigable weakness of the voluntary muscles and can exacerbate to life-threatening myasthenic crisis (MC), requiring intensive care treatment. Routine laboratory parameters are a cost-effective and widely available method for estimating the clinical outcomes of several diseases, but so far, such parameters have not been established to detect disease progression in MG.

Methods: We conducted a retrospective analysis of selected laboratory parameters related to inflammation and hemogram for MG patients with MC compared to MG patients without MC. To identify potential risk factors for MC, we applied time-varying Cox regression for time to MC and, as a sensitivity analysis, generalized estimating equations logistic regression for the occurrence of MC at the next patient visit.

Results: 15 of the 58 examined MG patients suffered at least one MC. There was no notable difference in the occurrence of MC by antibody status or sex. Both regression models showed that higher counts of basophils (per 0.01 unit increase: HR = 1.32, 95% CI = 1.02–1.70), neutrophils (per 1 unit increase: HR = 1.40, 95% CI = 1.14–1.72), potentially leukocytes (per 1 unit increase: HR = 1.15, 95% CI = 0.99–1.34), and platelets (per 100 units increase: HR = 1.54, 95% CI = 0.99–2.38) may indicate increased risk for a myasthenic crisis.

Conclusion: This pilot study provides proof of the concept that increased counts of basophils, neutrophils, leukocytes, and platelets may be associated with a higher risk of developing MC in patients with MG.

Patients with mutations in Cldn16 suffer from familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) which can lead to renal insufficiency. Mice lacking claudin-16 show hypomagnesemia and hypercalciuria, but no nephrocalcinosis. Calcium oxalate and calcium phosphate are the most common insoluble calcium salts that accumulate in the kidney in the case of nephrocalcinosis, however, the formation of these salts is less favored in acidic conditions. Therefore, urine acidification has been suggested to limit the formation of calcium deposits in the kidney. Assuming that urine acidification is causative for the absence of nephrocalcinosis in the claudin-16-deficient mouse model, we aimed to alkalinize the urine of these mice by the ablation of the subunit B1 of the vesicular ATPase in addition to claudin-16. In spite of an increased urinary pH in mice lacking claudin-16 and the B1 subunit, nephrocalcinosis did not develop. Thus, urinary acidification is not the only factor preventing nephrocalcinosis in claudin-16 deficient mice.

Functional avidity is supposed to critically shape the quality of immune responses, thereby influencing host protection against infectious agents including SARS-CoV-2. Here we show that after human SARS-CoV-2 vaccination, a large portion of high -avidity spike -specific CD4+ T cells lost CD3 expression after in vitro activation. The CD3- subset was enriched for cytokine-positive cells, including elevated per -cell expression levels, and showed increased polyfunctionality. Assessment of key metabolic pathways by flow cytometry revealed that superior functionality was accompanied by a shift toward fatty acid synthesis at the expense of their oxidation, whereas glucose transport and glycolysis were similarly regulated in SARS-CoV-2-specific CD3- and CD3+ subsets. As opposed to their CD3+ counterparts, frequencies of vaccine -specific CD3- T cells positively correlated with both the size of the naive CD4+ T cell pool and vaccine -specific IgG levels. Moreover, their frequencies negatively correlated with advancing age and were impaired in patients under immunosuppressive therapy. Typical recall antigen-reactive T cells showed a comparable segregation into functionally and metabolically distinct CD3+ and CD3- subsets but were quantitatively maintained upon aging, likely due to earlier recruitment in life. In summary, our data identify CD3- T helper cells as correlates of high -quality immune responses that are impaired in at -risk populations.

This paper introduces a dataset from a validation study of two psychometric models, one on the intraindividual speed-ability relationship and the other one on persistence. It includes responses, response times, and action sequences from N = 1244 participants who completed a matrix reasoning test under two experimental conditions, one being speeded and one being non-speeded. Additionally, it includes measures on motivational disposition, current motivation, effort, and concentration. Collected online via Prolific, the data is freely available at OSF (https://osf.io/9j6hm/). This dataset may aid in the development and validation of psychometric models on response processes as well as the investigation of test-taking behavior.

Background: Although commercially developed automated insulin delivery (AID) systems have recently been approved and become available in a limited number of countries, they are not universally available, accessible, or affordable. Therefore, open-source AID systems, cocreated by an online community of people with diabetes and their families behind the hashtag #WeAreNotWaiting, have become increasingly popular.

Objective: This study focused on examining the lived experiences, physical and emotional health implications of people with diabetes following the initiation of open-source AID systems, their perceived challenges, and their sources of support, which have not been explored in the existing literature.

Methods: We collected data from 383 participants across 29 countries through 2 sets of open-ended questions in a web-based survey on their experience of building and using open-source AID systems. Narratives were thematically analyzed, and a coding framework was identified through iterative alignment.

Results: Participants consistently reported improvements in glycemia, physical health, sleep quality, emotional impact on everyday life, and quality of life. Knowledge of open-source AID systems was largely obtained through the #WeAreNotWaiting community, which was also the primary source of practical and emotional support. The acquisition of the components to build an open-source AID system and the technical setup were sometimes problematic.

Conclusions: The #WeAreNotWaiting movement represents a primary example of how informed and connected patients proactively address their unmet needs, provide peer support to each other, and obtain results through impactful, user-driven solutions. Alongside providing evidence on the safety and efficacy of open-source AID systems, this qualitative analysis helps in understanding how patients’ experiences and benefits range from psychosocial improvements to a reduction in the burden of managing diabetes.

Background: The optimal fixation technique in periacetabular osteotomy (PAO) remains controversial. Modified fixation with Kirschner wires (K-wires) was described as a feasible and safe alternative. However, clinical follow-up of patients treated with this technique is lacking. Aims: To assess patient-reported outcomes (PROMs) in patients treated with PAO with the K-wire fixation technique and to compare it with the screw fixation technique. Methods: We conducted an analysis of 202 consecutive PAOs at a single university center between January 2015 and June 2017. A total of 120 cases with complete datasets were included in the final analysis. PAOs with K-wire fixation (n = 63) were compared with screw fixation (n = 57). Mean follow-up was 63 ± 10 months. PROMs assessed included the International Hip Outcome Tool (iHOT 12), Subjective Hip Value (SHV), and UCLA activity score (UCLA). Pain and patient satisfaction (NRS) were evaluated. Joint preservation was defined as non-conversion to total hip arthroplasty (THA). Results: Preoperative baseline PROMs in both fixation groups were similar. In both groups, PROMs (p = <0.001) and pain (p = <0.001) improved significantly. Postoperative functional outcome was similar in both groups: iHOT 12 (71.8 ± 25.1 vs. 73 ± 21.1; p = 0.789), SHV (77.9 ± 21.2 vs. 82.4 ± 13.1; p = 0.192), UCLA (6.9 ± 1.6 vs. 6.9 ± 1.9; p = 0.909), and pain (2.4 ± 2.1 vs. 2.0 ± 2.1; p = 0.302). Patient satisfaction did not differ significantly (7.6 ± 2.6 vs. 8.2 ± 2.2; p = 0.170). Conversion to THA was low in both groups (two vs. none; p = 0.497). Conclusion: Periacetabular osteotomy with K-wire fixation provided good clinical results at mid-term follow-up, comparable to those of screw fixation. The technique can therefore be considered a viable option when deciding on the fixation technique in PAO.