Lithium tantalate photonic integrated circuits for volume manufacturing.

Electro-optical photonic integrated circuits (PICs) based on lithium niobate (LiNbO3) have demonstrated the vast capabilities of materials with a high Pockels coefficient1,2. They enable linear and high-speed modulators operating at complementary metal-oxide-semiconductor voltage levels3 to be used in applications including data-centre communications4, high-performance computing and photonic accelerators for AI5. However, industrial use of this technology is hindered by the high cost per wafer and the limited wafer size. The high cost results from the lack of existing high-volume applications in other domains of the sort that accelerated the adoption of silicon-on-insulator (SOI) photonics, which was driven by vast investment in microelectronics. Here we report low-loss PICs made of lithium tantalate (LiTaO3), a material that has already been adopted commercially for 5G radiofrequency filters6 and therefore enables scalable manufacturing at low cost, and it has equal, and in some cases superior, properties to LiNbO3. We show that LiTaO3 can be etched to create low-loss (5.6 dB m-1) PICs using a deep ultraviolet (DUV) stepper-based manufacturing process7. We demonstrate a LiTaO3 Mach-Zehnder modulator (MZM) with a half-wave voltage-length product of 1.9 V cm and an electro-optic bandwidth of up to 40 GHz. In comparison with LiNbO3, LiTaO3 exhibits a much lower birefringence, enabling high-density circuits and broadband operation over all telecommunication bands. Moreover, the platform supports the generation of soliton microcombs. Our work paves the way for the scalable manufacture of low-cost and large-volume next-generation electro-optical PICs.

OrganoIDNet: a deep learning tool for identification of therapeutic effects in PDAC organoid-PBMC co-cultures from time-resolved imaging data.

PURPOSE: Pancreatic Ductal Adenocarcinoma (PDAC) remains a challenging disease due to its complex biology and aggressive behavior with an urgent need for efficient therapeutic strategies. To assess therapy response, pre-clinical PDAC organoid-based models in combination with accurate real-time monitoring are required. METHODS: We established stable live-imaging organoid/peripheral blood mononuclear cells (PBMCs) co-cultures and introduced OrganoIDNet, a deep-learning-based algorithm, capable of analyzing bright-field images of murine and human patient-derived PDAC organoids acquired with live-cell imaging. We investigated the response to the chemotherapy gemcitabine in PDAC organoids and the PD-L1 inhibitor Atezolizumab, cultured with or without HLA-matched PBMCs over time. Results obtained with OrganoIDNet were validated with the endpoint proliferation assay CellTiter-Glo. RESULTS: Live cell imaging in combination with OrganoIDNet accurately detected size-specific drug responses of organoids to gemcitabine over time, showing that large organoids were more prone to cytotoxic effects. This approach also allowed distinguishing between healthy and unhealthy status and measuring eccentricity as organoids' reaction to therapy. Furthermore, imaging of a new organoids/PBMCs sandwich-based co-culture enabled longitudinal analysis of organoid responses to Atezolizumab, showing an increased potency of PBMCs tumor-killing in an organoid-individual manner when Atezolizumab was added. CONCLUSION: Optimized PDAC organoid imaging analyzed by OrganoIDNet represents a platform capable of accurately detecting organoid responses to standard PDAC chemotherapy over time. Moreover, organoid/immune cell co-cultures allow monitoring of organoid responses to immunotherapy, offering dynamic insights into treatment behavior within a co-culture setting with PBMCs. This setup holds promise for real-time assessment of immunotherapeutic effects in individual patient-derived PDAC organoids.

Prospective measurement of the width of cerebrospinal fluid spaces by cranial ultrasound in neurologically healthy children aged 0-19 months.

BACKGROUND: Ultrasound (US) is often the first method used to look for brain or cerebrospinal fluid (CSF) space pathologies. Knowledge of normal CSF width values is essential. Most of the available US normative values were established over 20 years ago, were obtained with older equipment, and cover only part of the age spectrum that can be examined by cranial US. This prospective study aimed to determine the normative values of the widths of the subarachnoid and internal CSF spaces (craniocortical, minimal and maximal interhemispheric, interventricular, and frontal horn) for high-resolution linear US probes in neurologically healthy infants and children aged 0-19 months and assess whether subdural fluid collections can be delineated. METHODS: Two radiologists measured the width of the CSF spaces with a conventional linear probe and an ultralight hockey-stick probe in neurologically healthy children not referred for cranial or spinal US. RESULTS: This study included 359 neurologically healthy children (nboys = 178, 49.6%; ngirls = 181, 50.4%) with a median age of 46.0 days and a range of 1-599 days. We constructed prediction plots, including the 5th, 50th, and 95th percentiles, and an interactive spreadsheet to calculate normative values for individual patients. The measurements of the two probes and the left and right sides did not differ, eliminating the need for separate normative values. No subdural fluid collection was detected. CONCLUSION: Normative values for the widths of the subarachnoid space and the internal CSF spaces are useful for evaluating intracranial pathology, especially when determining whether an increase in the subarachnoid space width is abnormal.

Mechanically induced correlated errors on superconducting qubits with relaxation times exceeding 0.4 ms.

Superconducting qubits are among the most advanced candidates for achieving fault-tolerant quantum computing. Despite recent significant advancements in the qubit lifetimes, the origin of the loss mechanism for state-of-the-art qubits is still subject to investigation. Furthermore, the successful implementation of quantum error correction requires negligible correlated errors between qubits. Here, we realize long-lived superconducting transmon qubits that exhibit fluctuating lifetimes, averaging 0.2 ms and exceeding 0.4 ms - corresponding to quality factors above 5 million and 10 million, respectively. We then investigate their dominant error mechanism. By introducing novel time-resolved error measurements that are synchronized with the operation of the pulse tube cooler in a dilution refrigerator, we find that mechanical vibrations from the pulse tube induce nonequilibrium dynamics in highly coherent qubits, leading to their correlated bit-flip errors. Our findings not only deepen our understanding of the qubit error mechanisms but also provide valuable insights into potential error-mitigation strategies for achieving fault tolerance by decoupling superconducting qubits from their mechanical environments.

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

BACKGROUND: Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. METHODS: Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. RESULTS: Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. CONCLUSIONS: Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

Unused potential of lipid-lowering therapy in very high-risk patients with atherosclerotic cardiovascular disease. A retrospective data analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in Europe. Although the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidaemias claim a target low-density lipoprotein cholesterol (LDL-C) value of <55 mg/dL for very high-risk patients by use of lipid-lowering therapy (LLT) and lifestyle adaptations, the target level achievement is not satisfactory. We examined LLT use in ASCVD patients exceeding LDL-C target levels at admission and its adaptations at discharge. METHODS AND RESULTS: Between January 2017 and February 2020, 1091 patients with LDL-C >100 mg/dL and ASCVD defined as diagnosis of angina pectoris (AP, n = 179), acute myocardial infarction (AMI, n = 317), chronic ischemic heart disease (CHD, n = 195), or peripheral artery disease (PAD, n = 400) were extracted from hospital records. LLT use on admission and discharge as well as recommendations on lifestyle and nutrition were analysed. On admission, 51% of the patients were not taking LLT. At discharge, 91% were prescribed statins and 87% were advised on lifestyle adaptation and/or pharmacological treatment. High-intensity statin use at discharge was present in 63% of the AP-group, 92% of the AMI-group, 62% of the CHD-group and 71% of the PAD-group. Ezetimibe was present in 16% and proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) in 1%. However, of those on high-intensity statin, 25% remained on insufficient statin dosage. CONCLUSION: Switch to high-intensity statins and use of ezetimibe and PCSK9i was low in chronic ASCVD patients. Even though statin intake was high in high-risk patients, target levels were still not reached.

Intravenous Opioid Medication with Piritramide Reduces the Risk of Pneumothorax During CT-Guided Percutaneous Core Biopsy of the Lung.

PURPOSE: CT-guided percutaneous core biopsy of the lung is usually performed under local anesthesia, but can also be conducted under additional systemic opioid medication. The purpose of this retrospective study was to assess the effect of intravenous piritramide application on the pneumothorax rate and to identify risk factors for post-biopsy pneumothorax. MATERIALS AND METHODS: One hundred and seventy-one core biopsies of the lung were included in this retrospective single center study. The incidence of pneumothorax and chest tube placement was evaluated. Patient-, procedure- and target-related variables were analyzed by univariate and multivariable logistic regression analysis. RESULTS: The overall incidence of pneumothorax was 39.2% (67/171). The pneumothorax rate was 31.5% (29/92) in patients who received intravenous piritramide and 48.1% (38/79) in patients who did not receive piritramide. In multivariable logistic regression analysis periinterventional piritramide application proved to be the only independent factor to reduce the risk of pneumothorax (odds ratio 0.46, 95%-confidence interval 0.24, 0.88; p = 0.018). Two or more pleura passages (odds ratio 3.38, 95%-confidence interval: 1.15, 9.87; p = 0.026) and prone position of the patient (odds ratio 2.27, 95%-confidence interval: 1.04, 4.94; p = 0.039) were independent risk factors for a higher pneumothorax rate. CONCLUSION: Procedural opioid medication with piritramide proved to be a previously undisclosed factor decreasing the risk of pneumothorax associated with CT-guided percutaneous core biopsy of the lung. LEVEL OF EVIDENCE 4: small study cohort.

Emergence of fractal geometries in the evolution of a metabolic enzyme.

Fractals are patterns that are self-similar across multiple length-scales1. Macroscopic fractals are common in nature2-4; however, so far, molecular assembly into fractals is restricted to synthetic systems5-12. Here we report the discovery of a natural protein, citrate synthase from the cyanobacterium Synechococcus elongatus, which self-assembles into Sierpinski triangles. Using cryo-electron microscopy, we reveal how the fractal assembles from a hexameric building block. Although different stimuli modulate the formation of fractal complexes and these complexes can regulate the enzymatic activity of citrate synthase in vitro, the fractal may not serve a physiological function in vivo. We use ancestral sequence reconstruction to retrace how the citrate synthase fractal evolved from non-fractal precursors, and the results suggest it may have emerged as a harmless evolutionary accident. Our findings expand the space of possible protein complexes and demonstrate that intricate and regulatable assemblies can evolve in a single substitution.

Photonic-electronic integrated circuit-based coherent LiDAR engine.

Chip-scale integration is a key enabler for the deployment of photonic technologies. Coherent laser ranging or FMCW LiDAR, a perception technology that benefits from instantaneous velocity and distance detection, eye-safe operation, long-range, and immunity to interference. However, wafer-scale integration of these systems has been challenged by stringent requirements on laser coherence, frequency agility, and the necessity for optical amplifiers. Here, we demonstrate a photonic-electronic LiDAR source composed of a micro-electronic-based high-voltage arbitrary waveform generator, a hybrid photonic circuit-based tunable Vernier laser with piezoelectric actuators, and an erbium-doped waveguide amplifier. Importantly, all systems are realized in a wafer-scale manufacturing-compatible process comprising III-V semiconductors, silicon nitride photonic integrated circuits, and 130-nm SiGe bipolar complementary metal-oxide-semiconductor (CMOS) technology. We conducted ranging experiments at a 10-meter distance with a precision level of 10 cm and a 50 kHz acquisition rate. The laser source is turnkey and linearization-free, and it can be seamlessly integrated with existing focal plane and optical phased array LiDAR approaches.

Infrared spectroscopy reveals metal-independent carbonic anhydrase activity in crotonyl-CoA carboxylase/reductase.

The conversion of CO2 by enzymes such as carbonic anhydrase or carboxylases plays a crucial role in many biological processes. However, in situ methods following the microscopic details of CO2 conversion at the active site are limited. Here, we used infrared spectroscopy to study the interaction of CO2, water, bicarbonate, and other reactants with ß-carbonic anhydrase from Escherichia coli (EcCA) and crotonyl-CoA carboxylase/reductase from Kitasatospora setae (KsCcr), two of the fastest CO2-converting enzymes in nature. Our data reveal that KsCcr possesses a so far unknown metal-independent CA-like activity. Site-directed mutagenesis of conserved active site residues combined with molecular dynamics simulations tracing CO2 distributions in the active site of KsCCr identify an 'activated' water molecule forming the hydroxyl anion that attacks CO2 and yields bicarbonate (HCO3-). Computer simulations also explain why substrate binding inhibits the anhydrase activity. Altogether, we demonstrate how in situ infrared spectroscopy combined with molecular dynamics simulations provides a simple yet powerful new approach to investigate the atomistic reaction mechanisms of different enzymes with CO2.

Role of PAR1 -506 deletion/insertion polymorphism in primary sclerosing cholangitis.

AIM: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by inflammation of the intra- and extrahepatic bile ducts. Pathogenesis of PSC is still enigmatic but is likely to be multifactorial. Recently, we identified an interleukin-6 (IL-6)-dependent signal transducer and activator of transcription 3 (STAT3) activation in CD4+ TH1 and TH17 cells in PSC. The IL-6/STAT3 pathway was shown to be regulated by protease-activated receptor 1 (PAR1) contributing to inflammation. The role of the PAR1 -506 deletion/insertion (Del/Ins) polymorphism in PSC has not yet been investigated. METHODS: Two hundred eighty four PSC patients (200 patients with inflammatory bowel diseases [IBD] and 84 without IBD) and 309 healthy controls were genotyped for PAR1 rs11267092 (-506 Del/Ins -13 bp). Results were correlated with clinical characteristics and transplant-free survival. RESULTS: The frequency of PAR1 -506 Ins allele carriers (Del/Ins and Ins/Ins) was significantly higher in PSC patients (57.0%) compared to healthy controls (39.8%). Furthermore, carriers of PAR1 -506 Ins allele were more likely to have PSC than noncarriers (odds ratio 2.01; 95% confidence interval, 1.45-2.79). Patients with PSC carrying the PAR1 -506 Ins allele showed significantly higher alanine aminotransferase serum levels (p = 0.0357) and a trend toward shorter transplant-free survival time compared to noncarriers (8.9 ± 6.6 years vs. 10.5 ± 7.1 years; p = 0.076). CONCLUSIONS: Our study shows that PAR1 -506 Ins is significantly more frequent in people with PSC. As PAR1 -506 Ins allele carriers tended to have a shorter transplant-free survival, PAR1 might play a role in the development and course of PSC.

Time-Series Modeling and Forecasting of Cerebral Pressure-Flow Physiology: A Scoping Systematic Review of the Human and Animal Literature.

The modeling and forecasting of cerebral pressure-flow dynamics in the time-frequency domain have promising implications for veterinary and human life sciences research, enhancing clinical care by predicting cerebral blood flow (CBF)/perfusion, nutrient delivery, and intracranial pressure (ICP)/compliance behavior in advance. Despite its potential, the literature lacks coherence regarding the optimal model type, structure, data streams, and performance. This systematic scoping review comprehensively examines the current landscape of cerebral physiological time-series modeling and forecasting. It focuses on temporally resolved cerebral pressure-flow and oxygen delivery data streams obtained from invasive/non-invasive cerebral sensors. A thorough search of databases identified 88 studies for evaluation, covering diverse cerebral physiologic signals from healthy volunteers, patients with various conditions, and animal subjects. Methodologies range from traditional statistical time-series analysis to innovative machine learning algorithms. A total of 30 studies in healthy cohorts and 23 studies in patient cohorts with traumatic brain injury (TBI) concentrated on modeling CBFv and predicting ICP, respectively. Animal studies exclusively analyzed CBF/CBFv. Of the 88 studies, 65 predominantly used traditional statistical time-series analysis, with transfer function analysis (TFA), wavelet analysis, and autoregressive (AR) models being prominent. Among machine learning algorithms, support vector machine (SVM) was widely utilized, and decision trees showed promise, especially in ICP prediction. Nonlinear models and multi-input models were prevalent, emphasizing the significance of multivariate modeling and forecasting. This review clarifies knowledge gaps and sets the stage for future research to advance cerebral physiologic signal analysis, benefiting neurocritical care applications.

Premorbid body weight predicts weight loss in both anorexia nervosa and atypical anorexia nervosa: Further support for a single underlying disorder.

OBJECTIVE: For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. METHOD: Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. RESULTS: Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. DISCUSSION: Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. PUBLIC SIGNIFICANCE: Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

[Liver transplantation in viral and autoimmune liver diseases]. / Lebertransplantation bei viralen und autoimmunen Lebererkrankungen.

BACKGROUND: Despite substantial progress in the management of viral and autoimmune liver diseases, these entities remain relevant indications for liver transplantation. AIMS: To provide an overview of the current knowledge regarding the management of viral and autoimmune liver diseases before and after liver transplantation. MATERIALS AND METHODS: Selective literature search, including current guidelines and abstracts of key scientific meetings. RESULTS AND DISCUSSION: Viral and autoimmune liver disease can be effectively treated in most cases, which has resulted in an overall decline in liver transplantations for this indication group. However, hepatitis D infection and primary sclerosing cholangitis remain difficult-to-treat liver diseases in some patients and may progress to end-stage liver disease despite best possible management. Viral or autoimmune hepatitis can lead to fulminant liver failure requiring emergency liver transplantation. In patients who are transplanted due to viral or autoimmune liver disease, specific measures to prevent recurrence of these diseases after transplantation are mandatory. In view of effective treatment modalities for chronic hepatitis B and C, even liver grafts from donors infected with these viruses can be considered for liver transplantation under certain circumstances.

A recently quenched galaxy 700 million years after the Big Bang.

Local and low-redshift (z < 3) galaxies are known to broadly follow a bimodal distribution: actively star-forming galaxies with relatively stable star-formation rates and passive systems. These two populations are connected by galaxies in relatively slow transition. By contrast, theory predicts that star formation was stochastic at early cosmic times and in low-mass systems1-4. These galaxies transitioned rapidly between starburst episodes and phases of suppressed star formation, potentially even causing temporary quiescence-so-called mini-quenching events5,6. However, the regime of star-formation burstiness is observationally highly unconstrained. Directly observing mini-quenched galaxies in the primordial Universe is therefore of utmost importance to constrain models of galaxy formation and transformation7,8. Early quenched galaxies have been identified out to redshift z < 5 (refs. 9-12) and these are all found to be massive (M⋆ > 1010 M⊙) and relatively old. Here we report a (mini-)quenched galaxy at z = 7.3, when the Universe was only 700 Myr old. The JWST/NIRSpec spectrum is very blue (U-V = 0.16 ± 0.03 mag) but exhibits a Balmer break and no nebular emission lines. The galaxy experienced a short starburst followed by rapid quenching; its stellar mass (4-6 × 108 M⊙) falls in a range that is sensitive to various feedback mechanisms, which can result in perhaps only temporary quenching.

Role and relevance of dentists in a multiprofessional palliative care team: results of a cross-sectional survey study.

PURPOSE: Despite the multiprofessional concept surrounding palliative care patients (PCPs) and their high prevalence of oral issues, licensed dentists (LDs) are often not included in their treatment team. This study aimed to examine the current state of cooperation and to determine whether and how LDs should be included in the care for PCPs. METHODS: This single-centre cross-sectional study was conducted at the University Hospital Muenster, Germany. We surveyed three participant groups: PCPs, LDs, and healthcare professionals (HCPs). Questionnaires were tailored for each group, with some questions common for comparison. RESULTS: The study encompassed the results of 48 questionnaires from LDs, 50 from PCPs along with 50 from HCPs. Consensus was reached among all parties (LDs: 73% (n = 35/48); HCPs: 94%, n = 47/50; PCPs: 60%, n = 30/50) that involving LDs in the treatment concept is favourable. On the other hand, a significant discrepancy emerged in the perception of the dental treatment effort required by PCPs. While LDs (81%; n = 39/48) and HCPs (64%; n = 32/50) were convinced of increased effort, PCPs (34%; n = 17/50) largely did not share this perspective. To enhance patient care and formulate appropriate treatment plans, LDs consider both training (58%; n = 28/48) and guidebooks (71%; n = 34/48) to be valuable and would attend or use such resources. CONCLUSION: This study sheds light on the current gaps in including LDs in palliative care teams and emphasizes the importance of multidisciplinary collaboration to address oral health needs effectively. Development of continuing education options and collaborative models between LDs and HCPs needs to be further expanded in future.

Room-temperature quantum optomechanics using an ultralow noise cavity.

At room temperature, mechanical motion driven by the quantum backaction of light has been observed only in pioneering experiments in which an optical restoring force controls the oscillator stiffness1,2. For solid-state mechanical resonators in which oscillations are controlled by the material rigidity, the observation of these effects has been hindered by low mechanical quality factors, optical cavity frequency fluctuations3, thermal intermodulation noise4,5 and photothermal instabilities. Here we overcome these challenges with a phononic-engineered membrane-in-the-middle system. By using phononic-crystal-patterned cavity mirrors, we reduce the cavity frequency noise by more than 700-fold. In this ultralow noise cavity, we insert a membrane resonator with high thermal conductance and a quality factor (Q) of 180 million, engineered using recently developed soft-clamping techniques6,7. These advances enable the operation of the system within a factor of 2.5 of the Heisenberg limit for displacement sensing8, leading to the squeezing of the probe laser by 1.09(1) dB below the vacuum fluctuations. Moreover, the long thermal decoherence time of the membrane oscillator (30 vibrational periods) enables us to prepare conditional displaced thermal states of motion with an occupation of 0.97(2) phonons using a multimode Kalman filter. Our work extends the quantum control of solid-state macroscopic oscillators to room temperature.

SARS-CoV-2 and Adolescent Psychiatric Emergencies at the Tübingen University Hospital: Analyzing Trends, Diagnoses, and Contributing Factors.

Psychiatric emergencies have increased in recent decades, particularly with the onset of the SARS-CoV-2 pandemic, and far too little is known about the backgrounds of these emergencies. In this study, we investigated the extent to which the number of psychiatric emergencies changed during and in the aftermath of the SARS-CoV-2 pandemic at the Child and Adolescent Psychiatry (CAP) Tübingen. We considered age and psychiatric diagnoses. Additionally, we evaluated the backgrounds of the emergencies. We applied a mixed- (quantitative and qualitative) methods approach to data on emergency presentations at the CAP Tübingen from the pre-SARS-CoV-2 pandemic period (October 2019-January 2020) to Restriction Phase 1 (October 2020-January 2021), Restriction Phase 2 (October 2021-January 2022), and endemic phase (October 2022-January 2023). The total number of emergencies and those with eating disorders and affective disorders increased, while obsessive-compulsive disorders, expansive disorders and anxiety disorders decreased. The patients presenting in the pre-SARS-CoV-2 pandemic period were younger than those in the subsequent periods. We content-coded the reasons behind the emergency presentations. We also identified four areas of stressors and personality characteristics associated with the emergency presentations. In light of the increasing number of psychiatric emergencies, the long-term aim should be to meet the growing demands and create options for prevention.