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Abstract Background Globally, healthcare institutions have seen a marked rise in workplace violence (WPV), especially since the Covid-19 pandemic began, affecting primarily acute care and emergency departments (EDs). At the University Health Network (UHN) in Toronto, Canada, WPV incidents in EDs jumped 169% from 0.43 to 1.15 events per 1000 visits (p

Abstract $$\varLambda $$ Λ -Cold Dark Matter ( $$\varLambda $$ Λ CDM) has been successful at explaining the large-scale structures in the universe but faces severe issues on smaller scales when compared to observations. Introducing self-interactions between dark matter particles claims to provide a solution to the small-scale issues in the $$\varLambda $$ Λ CDM simulations while being consistent with the observations at large scales. The existence of the energy region in which these self-interactions between dark matter particles come close to saturating the S-wave unitarity bound can result in the formation of dark matter bound states called darkonium. In this scenario, all the low energy scattering properties are determined by a single parameter, the inverse scattering length $$\gamma $$ γ . In this work, we set bounds on $$\gamma $$ γ by studying the impact of darkonium on the observations at direct detection experiments using data from CRESST-III and XENON1T. The exclusion limits on $$\gamma $$ γ are then subsequently converted to exclusion limits on the self-interaction cross-section and compared with the constraints from astrophysics and N-body simulations.

Abstract In recent times, the sensitivity of low-mass direct dark matter searches has been limited by unknown low energy backgrounds close to the energy threshold of the experiments known as the low energy excess (LEE). The CRESST experiment utilises advanced cryogenic detectors constructed with different types of crystals equipped with Transition Edge Sensors (TESs) to measure signals of nuclear recoils induced by the scattering of dark matter particles in the detector. In CRESST, this low energy background manifests itself as a steeply rising population of events below 200 eV. A novel detector design named doubleTES using two identical TESs on the target crystal was studied to investigate the hypothesis that the events are sensor-related. We present the first results from two such modules, demonstrating their ability to differentiate between events originating from the crystal’s bulk and those occurring in the sensor or in its close proximity.

Abstract Cryogenic scintillating calorimeters are ultra- sensitive particle detectors for rare event searches, particularly for the search for dark matter and the measurement of neutrino properties. These detectors are made from scintillating target crystals generating two signals for each particle interaction. The phonon (heat) signal precisely measures the deposited energy independent of the type of interacting particle. The scintillation light signal yields particle discrimination on an event-by-event basis. This paper presents a likelihood framework modeling backgrounds and a potential dark matter signal in the two-dimensional plane spanned by phonon and scintillation light energies. We apply the framework to data from CaWO $$_4$$ 4 -based detectors operated in the CRESST dark matter search. For the first time, a single likelihood framework is used in CRESST to model the data and extract results on dark matter in one step by using a profile likelihood ratio test. Our framework simultaneously fits (neutron) calibration data and physics (background) data and allows combining data from multiple detectors. Although tailored to CaWO $$_4$$ 4 -targets and the CRESST experiment, the framework can easily be expanded to other materials and experiments using scintillating cryogenic calorimeters for dark matter search and neutrino physics.

ABSTRACT This systematic review aims to identify whether electronic screens can influence head and neck posture in adolescents. This study was registered in PROSPERO and the databases used were EMBASE, LILACS, SciELO, PEDro, PubMed, and Scopus, with no language or publication date limitations. The keywords used were posture, neck, and adolescents. A total of 1,997 articles with duplicates were found, 1,858 articles were excluded after title reading and 65 after abstract reading. During the analysis of the full texts, 22 were excluded because they addressed individuals with an average age of less than 15 or more than 19 years, 10 did not refer to technology use, and three only evaluated symptomatic individuals, therefore, only four articles were reviewed. The methodological quality of the studies was defined according to the Newcastle Ottawa Quality Assessment Scale, with three being classified as good methodological quality and analyzing posture when using a computer, and one with poor quality that analyzed posture when using a smartphone. Therefore, regarding smartphone use, considerations are limited. Overall, computer use is not responsible for postural changes in the head and neck of adolescents; however, more studies are needed to confirm this conclusion.

Background: Biofortification of staple crops is a food-based strategy to reduce the high global burden of micronutrient deficiencies. Monitoring program performance is essential to ensure biofortification programs have high potential for impact; however, few indicators and methods for doing so are publicly available. Objective: We documented the set of standardized indicators and methods used to monitor the Commercialization of Biofortified Crops (CBC) program and reviewed their strengths and limitations. Methods: Following the CBC program impact pathway, we identified and defined a set of indicators and corresponding methods. Country-level implementation teams contextualized and operationalized them to monitor 9 country-crop programs (i.e., high iron beans in Kenya and Tanzania, iron pearl millet in India, vitamin A maize in Nigeria and Tanzania, vitamin A cassava in Nigeria, zinc wheat in Pakistan and India, and zinc rice in Bangladesh) from 2020 to 2022. Results: Twenty indicators were defined across domains of seed supply, production, availability, awareness, capacity development, advocacy, and consumption of biofortified foods. Data collection methods included external and internal document review, farmer household surveys, rapid market assessments, and modeling. The strengths of these methods were that they were rapid to conduct, low cost, and simple to use. For some methods, the limitations were the potentially reduced accuracy of some results due to the use of external data sources or secondary data inputs and unavailability of data. Conclusions: The indicators and methods used in the CBC program are practical and cost effective for monitoring the implementation of biofortification programs because they generate the range of information necessary to understand how effectively a program is delivered and bolster plausibility arguments for attributing observed impacts to program activities. Further testing is needed to confirm their generalizability when applied to different contexts and paired with impact evaluations with the aim of producing publicly available global guidance documents.

Purpose: This report describes a surgical approach involving a 5-layer closure performed for a patient with uveitic glaucoma who had an Ahmed Glaucoma Valve placed 12 years prior to presentation, then erosions which were revised 2 and 4 years ago. Additionally, the patient had a Descemet Stripping Endothelial Keratoplasty (DSEK) completed 4 years prior to presentation. The patient presented with a tube that was eroded and a DSEK that had failed. Observations: We describe the process of same-quadrant tube exchange for a new Baerveldt Glaucoma Implant-350 with repositioning of the tube tip from the anterior chamber to the ciliary sulcus with a 5-layer closure with Tutoplast pericardial patch graft, capsule autograft harvested from the Ahmed capsule, Tenon's transposition from a different quadrant, Tenon's advancement from the same quadrant, and conjunctival advancement. By post-operative month 16, the patient had undergone a repeat DSEK and had an improved visual acuity and well-controlled intraocular pressure on one IOP-lowering medication. Conclusions: In complex tube revision surgeries with melted sclera, difficult closure under tension, and/or presence of significant tissue defect, pericardial patch graft, capsule autograft, tenon's transposition, tenon's advancement, or conjunctival advancement should be considered, as needed.

Abstract Objective Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterized by recurrent ischemic/hemorrhagic strokes due to progressive occlusion of the intracranial carotid arteries. The lack of reliable disease severity biomarkers led us to investigate molecular features of a Caucasian cohort of MA patients. Methods The participants consisted of 30 MA patients and 40 controls. We measured cerebrospinal fluid (CSF) levels of angiogenic/inflammatory factors (ELISA). We then applied quantitative real‐time PCR on cerebral artery specimens for expression analyses of angiogenic factors. By an immunoassay based on microfluidic technology, we examined the potential correlations between plasma protein expression and MA clinical progression. A RNA interference approach toward Ring Finger Protein 213 (RNF213) and a tube formation assay were applied in cellular model. Results We detected a statistically significant (p 2) of MA patients compared to controls. A high Ang‐2 plasma concentration (p = 0.018) was associated with unfavorable outcome in a subset of MA patients. ROC curve analyses indicated Ang‐2 as diagnostic CSF biomarker (>3741 pg/mL) and prognostic plasma biomarker (>1162 pg/mL), to distinguish stable‐from‐progressive MA. Consistently, MA cellular model showed a significant up‐regulation (RQ >2) of Ang‐2 in RNF213 silenced condition. Interpretation Our results pointed out Ang‐2 as a reliable biomarker mirroring arterial steno‐occlusion and vascular instability of MA in CSF and blood, providing a candidate factor for patient stratification. This pilot study may pave the way to the validation of a biomarker to identify progressive MA patients deserving a specific treatment path.

This study investigates heat transfer efficiency and irreversibility generation in multi-sided porous thermal systems filled with a Cu-Al2O3-water hybrid nanofluid. The research examines convective heat transfer across various polygonal geometries, ranging from four-sided to infinitely-sided (circular) structures, aiming to maximize thermal system performance intended for scientific and industrial applications. For a standardized comparison, the fluid volume and active heating and cooling lengths are kept constant for all the geometries considered. The analysis includes varying flow-controlling variables like the modified Rayleigh number (Ram), Hartmann number (Ha), and Darcy number (Da) to evaluate how they affect heat transfer efficiency and entropy generation, including total, magnetic, and viscous entropy. The numerical simulations, conducted using the finite element approach, explore Ram values ranging from 10 to 104, Ha from 0 to 70, and Da from 10-4 to 10-2. Streamline and isothermal contours analyze flow behavior, while heatline tools reveal thermal energy transport dynamics. Results show up to a 20 % improvement in heat transfer efficiency in optimized configurations. Key findings indicate that hexagonal structures can be viable alternatives to circular tubes in space-constrained applications, offering comparable thermal performance. Interestingly, pentagonal cavities exhibit the highest irreversibility due to symmetry loss. The study offers insightful information for enhancing thermal system design in various industrial settings, particularly for applications requiring efficient heat transfer in limited spaces.

ABSTRACT Background Enfortumab vedotin, a fully human monoclonal antibody–drug conjugate (ADC) directed to Nectin‐4, prolonged overall survival (OS) versus standard chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma (mUC) previously receiving a programmed cell death protein 1/ligand 1 (PD‐1/L1) inhibitor and platinum‐based chemotherapy in the pivotal, phase 3 EV‐301 clinical trial, supporting global approvals of enfortumab vedotin monotherapy. This bridging study was the first to evaluate enfortumab vedotin monotherapy in previously treated Chinese patients with locally advanced or mUC. Methods EV‐203 was a multicenter, open‐label, phase 2 study (NCT04995419) assessing efficacy, safety/tolerability, pharmacokinetics (PK), and immunogenicity of enfortumab vedotin in 40 Chinese patients (PK analysis set, n = 13) with previously treated locally advanced or mUC. Patients received enfortumab vedotin 1.25 mg/kg (Days 1, 8, and 15). Primary endpoints included confirmed objective response rate (ORR) by the independent review committee (IRC) and PK parameters of ADC, total antibody (TAb), and free monomethyl auristatin E (MMAE). Secondary endpoints included investigator‐assessed confirmed ORR; investigator‐/IRC‐assessed duration of response (DOR), disease control rate (DCR), and progression‐free survival (PFS); OS; immunogenicity; and safety/tolerability. Results As of May 13, 2022, the median follow‐up was 6.5 months. Confirmed ORR was 37.5% (n/N = 15/40; 95% CI: 22.7%–54.2%) by IRC and 42.5% (n/N = 17/40; 95% CI: 27.0%–59.1%) by investigator assessment. By IRC, DCR was 72.5% (n = 29), median DOR was not reached, and median PFS was 4.7 months. Median OS was not reached. Endpoints assessed by investigators were consistent with IRC assessments. Two patients discontinued treatment for treatment‐related adverse events. No new safety signals were identified. ADC, TAb, and free MMAE were characterized in Chinese patients and consistent with previously characterized populations. The incidence of positive antitherapeutic antibodies postbaseline was 0%. Conclusion Enfortumab vedotin demonstrated meaningful clinical activity with a manageable safety profile in Chinese patients with previously treated locally advanced or mUC. Trial Registration ClinicalTrials.gov identifier: NCT04995419

Abstract Diamond operated as a cryogenic calorimeter is an excellent target for direct detection of low-mass dark matter candidates. Following the realization of the first low-threshold cryogenic detector that uses diamond as absorber for astroparticle physics applications, we now present the resulting exclusion limits on the elastic spin-independent interaction cross-section of dark matter with diamond. We measured two 0.175 g CVD (Chemical Vapor Deposition) diamond samples, each instrumented with a Transition Edge Sensor made of Tungsten (W-TES). Thanks to the energy threshold of just 16.8 eV of one of the two detectors, we set exclusion limits on the elastic spin-independent interaction of dark matter particles with carbon nuclei down to dark matter masses as low as 0.122 GeV/c $$^2$$ 2 . This work shows the scientific potential of cryogenic detectors made from diamond and lays the foundation for the use of this material as target for direct detection dark matter experiments.

Background Workplace violence (WPV) is a complex global challenge in healthcare that can only be addressed through a quality improvement initiative composed of a complex intervention. However, multiple WPV-specific quality indicators are required to effectively monitor WPV and demonstrate an intervention’s impact. This study aims to determine a set of quality indicators capable of effectively monitoring WPV in healthcare.Methods This study used a modified Delphi process to systematically arrive at an expert consensus on relevant WPV quality indicators at a large, multisite academic health science centre in Toronto, Canada. The expert panel consisted of 30 stakeholders from the University Health Network (UHN) and its affiliates. Relevant literature-based quality indicators which had been identified through a rapid review were categorised according to the Donabedian model and presented to experts for two consecutive Delphi rounds.Results 87 distinct quality indicators identified through the rapid review process were assessed by our expert panel. The surveys received an average response rate of 83.1% in the first round and 96.7% in the second round. From the initial set of 87 quality indicators, our expert panel arrived at a consensus on 17 indicators including 7 structure, 6 process and 4 outcome indicators. A WPV dashboard was created to provide real-time data on each of these indicators.Conclusions Using a modified Delphi methodology, a set of quality indicators validated by expert opinion was identified measuring WPV specific to UHN. The indicators identified in this study were found to be operationalisable at UHN and will provide longitudinal quality monitoring. They will inform data visualisation and dissemination tools which will impact organisational decision-making in real time.

In the context of the stream calculus, we present an Implicit Function Theorem (IFT) for polynomial systems, and discuss its relations with the classical IFT from calculus. In particular, we demonstrate the advantages of the stream IFT from a computational point of view, and provide a few example applications where its use turns out to be valuable.

Background This case study describes and analyses an action research initiative undertaken by management, staff and World Health Organization (WHO) at the IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, Italy. The initiative utilised staff engagement approaches developed during the COVID-19 pandemic to rethink and reshape future development plans. The initiative provides a ‘how-to’ case study for complex health facilities on ways to create similar multisectoral, inclusive and holistic processes in planning structural, functional and organizational solutions for their ‘hospitals of tomorrow.’Methods The case study utilised an action research approach coordinated by a team of WHO facilitators in close collaboration with the Board of Hospital Directors. Heterogeneous and multidisciplinary working groups were created, with members from different levels of the hospital staff. In the context of facilitated group meetings held weekly over a one-year period, participants were asked to review topics of interest to future plans of the hospital and make recommendations on effective/innovative ways of addressing these in the short and long term. Working groups focused on different challenges.Results The initiative was successful in creating and sustaining broad staff engagement in the future planning processes. 80% groups maintained high staff participation throughout the entire project year. Participating staff reported enhanced communication and cooperation between departments represented in different groups. 87% of the proposed plans suggested by the working groups were approved by the Board for implementation.Conclusion Key factors contributing to the high approval rate of plans, strong engagement record of staff and enhanced cooperation between involved departments; included: multisectoral/cross hierarchal staff involvement, group attention to defining time-bound contextual goals, flexible implementation monitoring approaches, personnel skills and profiles of participants, direct and open communication at all levels and times, member commitment and clear exit strategy. The case study is presented as a model to stimulate similar actions in other complex healthcare facilities.