Quantum correlations of light due to a room temperature mechanical oscillator for force metrology

The coupling of laser light to a mechanical oscillator via radiation pressure leads to the emergence of quantum mechanical correlations between the amplitude and phase quadrature of the laser beam. These correlations form a generic non-classical resource which can be employed for quantum-enhanced force metrology, and give rise to ponderomotive squeezing in the limit of strong correlations. To date, this resource has only been observed in a handful of cryogenic cavity optomechanical experiments. Here, we demonstrate the ability to efficiently resolve optomechanical quantum correlations imprinted on an optical laser field interacting with a room temperature nanomechanical oscillator. Direct measurement of the optical field in a detuned homodyne detector ("variational measurement") at frequencies far from the resonance frequency of the oscillator reveal quantum correlations at the few percent level. We demonstrate how the absolute visibility of these correlations can be used for a quantum-enhanced estimation of the quantum back-action force acting on the oscillator, and provides for an enhancement in the relative signal-to-noise ratio for the estimation of an off-resonant external force, even at room temperature

The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells

Shank proteins, initially also described as ProSAP proteins, are scaffolding adaptors that have been previously shown to integrate neurotransmitter receptors into the cortical cytoskeleton at postsynaptic densities. We show here that Shank proteins are also crucial in receptor tyrosine kinase signaling. The PDZ domain–containing Shank3 protein was found to represent a novel interaction partner of the receptor tyrosine kinase Ret, which binds specifically to a PDZ-binding motif present in the Ret9 but not in the Ret51 isoform. Furthermore, we show that Ret9 but not Ret51 induces epithelial cells to form branched tubular structures in three-dimensional cultures in a Shank3-dependent manner. Ret9 but not Ret51 has been previously shown to be required for kidney development. Shank3 protein mediates sustained Erk–MAPK and PI3K signaling, which is crucial for tubule formation, through recruitment of the adaptor protein Grb2. These results demonstrate that the Shank3 adaptor protein can mediate cellular signaling, and provide a molecular mechanism for the biological divergence between the Ret9 and Ret51 isoform

Eigenbehaviour as an Indicator of Cognitive Abilities

With growing use of machine learning algorithms and big data in health applications, digital measures, such as digital biomarkers, have become highly relevant in digital health. In this paper, we focus on one important use case, the long-term continuous monitoring of cognitive ability in older adults. Cognitive ability is a factor both for long-term monitoring of people living alone as well as a relevant outcome in clinical studies. In this work, we propose a new potential digital biomarker for cognitive abilities based on location eigenbehaviour obtained from contactless ambient sensors. Indoor location information obtained from passive infrared sensors is used to build a location matrix covering several weeks of measurement. Based on the eigenvectors of this matrix, the reconstruction error is calculated for various numbers of used eigenvectors. The reconstruction error in turn is used to predict cognitive ability scores collected at baseline, using linear regression. Additionally, classification of normal versus pathological cognition level is performed using a support-vector machine. Prediction performance is strong for high levels of cognitive ability but grows weaker for low levels of cognitive ability. Classification into normal and older adults with mild cognitive impairment, using age and the reconstruction error, shows high discriminative performance with an ROC AUC of 0.94. This is an improvement of 0.08 as compared with a classification with age only. Due to the unobtrusive method of measurement, this potential digital biomarker of cognitive ability can be obtained entirely unobtrusively—it does not impose any patient burden. In conclusion, the usage of the reconstruction error is a strong potential digital biomarker for binary classification and, to a lesser extent, for more detailed prediction of inter-individual differences in cognition

Eigenbehaviour as an Indicator of Cognitive Abilities.

With growing use of machine learning algorithms and big data in health applications, digital measures, such as digital biomarkers, have become highly relevant in digital health. In this paper, we focus on one important use case, the long-term continuous monitoring of cognitive ability in older adults. Cognitive ability is a factor both for long-term monitoring of people living alone as well as a relevant outcome in clinical studies. In this work, we propose a new potential digital biomarker for cognitive abilities based on location eigenbehaviour obtained from contactless ambient sensors. Indoor location information obtained from passive infrared sensors is used to build a location matrix covering several weeks of measurement. Based on the eigenvectors of this matrix, the reconstruction error is calculated for various numbers of used eigenvectors. The reconstruction error in turn is used to predict cognitive ability scores collected at baseline, using linear regression. Additionally, classification of normal versus pathological cognition level is performed using a support-vector machine. Prediction performance is strong for high levels of cognitive ability but grows weaker for low levels of cognitive ability. Classification into normal and older adults with mild cognitive impairment, using age and the reconstruction error, shows high discriminative performance with an ROC AUC of 0.94. This is an improvement of 0.08 as compared with a classification with age only. Due to the unobtrusive method of measurement, this potential digital biomarker of cognitive ability can be obtained entirely unobtrusively-it does not impose any patient burden. In conclusion, the usage of the reconstruction error is a strong potential digital biomarker for binary classification and, to a lesser extent, for more detailed prediction of inter-individual differences in cognition

Value of arterial blood gas analysis in patients with acute dyspnea: an observational study

ABSTRACT: INTRODUCTION: The diagnostic and prognostic value of arterial blood gas analysis (ABGA) parameters in unselected patients presenting with acute dyspnea to the Emergency Department (ED) is largely unknown. METHODS: We performed a post-hoc analysis of two different prospective studies to investigate the diagnostic and prognostic value of ABGA parameters in patients presenting to the ED with acute dyspnea. RESULTS: We enrolled 530 patients (median age 74 years). ABGA parameters were neither useful to distinguish between patients with pulmonary disorders and other causes of dyspnea nor to identify specific disorders responsible for dyspnea. Only in patients with hyperventilation from anxiety disorder, the diagnostic accuracy of pH and hypoxemia rendered valuable with an area under the receiver operating characteristics curve (AUC) of 0.86. Patients in the lowest pH tertile more often required admission to Intensive Care Unit (28% vs 12% in the first tertile, P >0.001) and had higher in-hospital (14% vs 5%, P =0.003) and 30-day mortality (17% vs 7%, P =0.002). Cumulative mortality rate was higher in the first (37%), than in the second (28%), and the third tertile (23%, P =0.005) during 12 months follow-up. pH at presentation was an independent predictor of 12-month mortality in multivariable Cox proportional hazard analysis both for patients with pulmonary (P =0.043) and non-pulmonary disorders (P =0.038). CONCLUSIONS: ABGA parameters provide limited diagnostic value in patients with acute dyspnea, but pH is an independent predictor of 12 months mortality

Establishing Consensus on Essential Resources for Musculoskeletal Trauma Care Worldwide: A Modified Delphi Study

BACKGROUND: Despite evidence that formalized trauma systems enhance patient functional outcomes and decrease mortality rates, there remains a lack of such systems globally. Critical to trauma systems are the equipment, materials, and supplies needed to support care, which vary in availability regionally. The purpose of the present study was to identify essential resources for musculoskeletal trauma care across diverse resource settings worldwide. METHODS: The modified Delphi method was utilized, with 3 rounds of electronic surveys. Respondents consisted of 1 surgeon with expertise in musculoskeletal trauma per country. Participants were identified with use of the AO Trauma, AO Alliance, Orthopaedic Trauma Association, and European Society for Trauma and Emergency Surgery networks. Respondents rated resources on a Likert scale from 1 (most important) to 9 (least important). The "most essential" resources were classified as those rated ≤2 by ≥75% of the sampled group. RESULTS: One hundred and three of 111 invited surgeons completed the first survey and were included throughout the subsequent rounds (representing a 93% response rate). Most participants were fellowship-trained (78%) trauma and orthopaedic surgeons (90%) practicing in an academic setting (62%), and 46% had >20 years of experience. Respondents represented low-income and lower-middle-income countries (LMICs; 35%), upper-middle income countries (UMICs; 30%), and high-income countries (HICs; 35%). The initial survey identified 308 unique resources for pre-hospital, in-hospital, and post-hospital phases of care, of which 71 resources achieved consensus as the most essential. There was a significant difference (p < 0.0167) in ratings between income groups for 16 resources, all of which were related to general trauma care rather than musculoskeletal injury management. CONCLUSIONS: There was agreement on a core list of essential musculoskeletal trauma care resources by respondents from LMICs, UMICs, and HICs. All significant differences in resource ratings were related to general trauma management. This study represents a first step toward establishing international consensus and underscores the need to prioritize resources that are locally available. The information can be used to develop effective guidelines and policies, create best-practice treatment standards, and advocate for necessary resources worldwide. CLINICAL RELEVANCE: This study utilized the Delphi method representing expert opinion; however, this work did not examine patient management and therefore does not have a clinical Level of Evidence

Procalcitonin to Guide Initiation and Duration of Antibiotic Treatment in Acute Respiratory Infections: An Individual Patient Data Meta-Analysis

This individual patient data meta-analysis of clinical trials investigating procalcitonin algorithms for antibiotic decision making found no increased risk of death or setting-specific treatment failure but did find significantly lower antibiotic exposure across different acute respiratory infections and clinical setting

Association of Interprofessional Discharge Planning Using an Electronic Health Record Tool With Hospital Length of Stay Among Patients with Multimorbidity: A Nonrandomized Controlled Trial

Whether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial.; To evaluate the outcomes and safety associated with an electronic interprofessional-led discharge planning tool vs standard discharge planning to safely reduce length of stay among medical inpatients with multimorbidity.; This multicenter prospective nonrandomized controlled trial used interrupted time series analysis to examine medical acute hospitalizations at 82 hospitals in Switzerland. It was conducted from February 2017 through January 2019. Data analysis was conducted from March 2021 to July 2022.; After a 12-month preintervention phase (February 2017 through January 2018), an electronic interprofessional-led discharge planning tool was implemented in February 2018 in 7 intervention hospitals in addition to standard discharge planning.; Mixed-effects segmented regression analyses were used to compare monthly changes in trends of length of stay, hospital readmission, in-hospital mortality, and facility discharge after the implementation of the tool with changes in trends among control hospitals.; There were 54 695 hospitalizations at intervention hospitals, with 27 219 in the preintervention period (median [IQR] age, 72 [59-82] years; 14 400 [52.9%] men) and 27 476 in the intervention phase (median [IQR] age, 72 [59-82] years; 14 448 [52.6%] men) and 438 791 at control hospitals, with 216 261 in the preintervention period (median [IQR] age, 74 [60-83] years; 109 770 [50.8%] men) and 222 530 in the intervention phase (median [IQR] age, 74 [60-83] years; 113 053 [50.8%] men). The mean (SD) length of stay in the preintervention phase was 7.6 (7.1) days for intervention hospitals and 7.5 (7.4) days for control hospitals. During the preintervention phase, population-averaged length of stay decreased by -0.344 hr/mo (95% CI, -0.599 to -0.090 hr/mo) in control hospitals; however, no change in trend was observed among intervention hospitals (-0.034 hr/mo; 95% CI, -0.646 to 0.714 hr/mo; difference in slopes, P = .09). Over the intervention phase (February 2018 through January 2019), length of stay remained unchanged in control hospitals (slope, -0.011 hr/mo; 95% CI, -0.281 to 0.260 hr/mo; change in slope, P = .03), but decreased steadily among intervention hospitals by -0.879 hr/mo (95% CI, -1.607 to -0.150 hr/mo; change in slope, P = .04, difference in slopes, P = .03). Safety analyses showed no change in trends of hospital readmission, in-hospital mortality, or facility discharge over the whole study time.; In this nonrandomized controlled trial, the implementation of an electronic interprofessional-led discharge planning tool was associated with a decline in length of stay without an increase in hospital readmission, in-hospital mortality, or facility discharge.; isrctn.org Identifier: ISRCTN83274049

Long-term safety and effectiveness of canakinumab in patients with monogenic autoinflammatory diseases: results from the interim analysis of the RELIANCE registry

ObjectiveInterim analysis of the RELIANCE registry, an on-going, non-interventional, open-label, multicentre, prospective study evaluating the long-term safety, dosing regimens and effectiveness of canakinumab in patients with cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), tumour-necrosis factor receptor-associated periodic syndrome (TRAPS) or mevalonate-kinase deficiency (MKD)/hyperimmunoglobulin-D syndrome (HIDS).MethodsFrom September 2017 for patients with CAPS, and June 2018 for patients with FMF, TRAPS or MKD/HIDS, the registry enrolled paediatric (aged ≥2 years) and adult patients (aged ≥18 years) receiving canakinumab as part of their routine medical care. Safety, canakinumab dose, disease activity and quality of life outcome measures were evaluated at baseline and every 6 months until end of study visit.ResultsAt the analysis cut-off date (December 2020), 168 patients (91 CAPS, 54 FMF, 16 TRAPS and 7 MKD/HIDS) were enrolled. 85 (50.9%) patients were female and 72 (43.1%) were children (&lt;18 years). The median patient age was 20.0 years (range 2.0–79.0 years). In the CAPS cohort, serious infections and serious adverse drug-reactions were more common in patients receiving higher than the recommended starting dose (SD) of canakinumab. A trend to receive &gt;SD of canakinumab was observed in the pooled population. The majority of patients were reported as having either absent or mild/moderate disease activity (physician’s global assessment) from baseline to Month 30, with a stable proportion of patients (~70%) in remission under canakinumab treatment. Patient-reported disease activity (Visual Analogue Scale (VAS), Autoinflammatory Disease Activity Index), fatigue (VAS); markers of inflammation (C-reactive protein, serum amyloid A and erythrocyte sedimentation rate) remained well-controlled throughout.ConclusionData from this analysis confirm the long-term safety and effectiveness of canakinumab for the treatment of CAPS, FMF, TRAPS and MKD/HIDS.Novartis Pharma A