A global dataset of publicly available dengue case count data.

OpenDengue is a global database of dengue case data collated from public sources and standardised and formatted to facilitate easy reanalysis. Dataset version 1.2 of this database contains information on over 56 million dengue cases from 102 countries between 1924 and 2023, making it the largest and most comprehensive dengue case database currently available. Over 95% of records are at the weekly or monthly temporal resolution and subnational data is available for 40 countries. To build OpenDengue we systematically searched databases, ministry of health websites, peer reviewed literature and Pro-MED mail reports and extracted denominator-based case count data. We undertake standardisation and error checking protocols to ensure consistency and resolve discrepancies. We meticulously documented the extraction process to ensure records are attributable and reproducible. The OpenDengue database remains under development with plans for further disaggregation and user contributions are encouraged. This new dataset can be used to better understand the long-term drivers of dengue transmission, improve estimates of disease burden, targeting and evaluation of interventions and improving future projections.

Trends in incidence and average waiting time for arthroplasty from 1998-2021: an observational study of 282,367 patients from the Scottish arthroplasty project.

BACKGROUND: Current waiting times for arthroplasty are reported as being the worst on record. This is a combination of increasing demand, the COVID-19 pandemic and longer standing shortage of capacity. The Scottish Arthroplasty Project (SAP) is a National Audit that analyses all joint replacements undertaken in the Scottish NHS and Independent Sector. The aim of this study was to investigate the long-term trend in provision and waiting time for lower limb joint replacement surgery. METHODS: All total hip replacements (THR) and total knee replacements (TKR) undertaken in NHS Scotland from 1998 to 2021 were identified. Waiting times data were analysed each year to determine the minimum, maximum, median, mean and standard deviation. RESULTS: In 1998, there were 4,224 THR and 2,898 TKR with mean (range, SD) waiting time of 159.5 days (1-1,685, 119.8) and 182.9 days (1-1,946, 130.1). The minimum waiting times were both in 2013 for 7,612 THR - 78.8 days (0-539, 46) and 7,146 TKR - 79.1 days (0-489, 43.7). The maximum waiting times recorded were in 2021 with 4,070 THR waiting 283.7 days (0-945, 215) and 3,153 TKR waiting 316.8 days (4-1,064, 217). CONCLUSIONS: This is the first robust large-scale national dataset showing trends in incidence and waiting time for THR and TKR over two decades. There was an expansion of activity with a reduction in waiting time, which peaked in 2013, followed by an increase in waiting time with a plateau and modest decline in the number of procedures.

Comparison between continued inpatient treatment versus day patient treatment after short inpatient care in early onset anorexia nervosa (COTIDEA trial): a study protocol for a non-inferiority randomised controlled trial.

BACKGROUND: In children with early-onset anorexia nervosa (first symptoms before 13 years old, EO-AN), experts recommend initial outpatient treatment but in-patient treatment (IP) is frequently indicated due to acute medical instability or for those who have not improved with outpatient treatment. This IP can target either a partial weight restauration or a total weight normalization (return to the previous BMI growth trajectory). There are no evidence in the literature on which is the better therapeutic option in EOAN. But as long length of stay induce social isolation, with elevated costs, we wonder if a stepped-care model of daypatient treatment (DP) after short IP stabilisation may be a treatment option as effective as full-time IP to target weight normalization. We designed a two-arm randomised controlled trial testing the non-inferiority of a stepped-care model of DP after short IP stabilisation versus full-time IP. METHODS: Eighty-eight children aged 8 to 13 years suffering from EOAN with initial severe undernutrition will be randomly allocated to either IP treatment as usual or a stepped care DP model both targeting weight normalization. Assessments will be conducted at inclusion, somatic stabilization, weight normalization, 6 months and 12 months post randomisation. The primary outcome will be BMI at 12 months post-randomisation. Secondaries outcomes will included clinical (tanner stage), biological (prealbumin, leptin, total ghrelin and IGF1) and radiological (bone mineralization and maturation) outcomes, eating symptomatology and psychiatric assessments, motivation to change, treatment acceptability and quality of life assessments, cost-utility and cost-effectiveness analyses. DISCUSSION: COTIDEA will provide rigorous evaluation of treatment alternative to full-time inpatient treatment to allow a reduction of social iatrogenic link to hospital length of stay and associated costs. TRIAL REGISTRATION: Trial is registered on ClinicalTrials.gov (NCT04479683).

Cavity Quantum Optomechanical Nonlinearities and Position Measurement beyond the Breakdown of the Linearized Approximation.

Several optomechanics experiments are now entering the highly sought nonlinear regime where optomechanical interactions are large even for low light levels. Within this regime, new quantum phenomena and improved performance may be achieved; however, a corresponding theoretical formalism of cavity quantum optomechanics that captures the nonlinearities of both the radiation-pressure interaction and the cavity response is needed to unlock these capabilities. Here, we develop such a nonlinear cavity quantum optomechanical framework, which we then utilize to propose how position measurement can be performed beyond the breakdown of the linearized approximation. Our proposal utilizes optical general-dyne detection, ranging from single to dual homodyne, to obtain mechanical position information imprinted onto both the optical amplitude and phase quadratures and enables both pulsed and continuous modes of operation. These cavity optomechanical nonlinearities are now being confronted in a growing number of experiments, and our framework will allow a range of advances to be made in, e.g., quantum metrology, explorations of the standard quantum limit, and quantum measurement and control.

[Transbronchial lung cryobiopsy in interstitial lung diseases]. / Les cryobiopsies pulmonaires transbronchiques dans les pneumopathies infiltrantes diffuses.

In some cases of interstitial lung disease (ILD), clinical and biological findings associated with CT scan pattern during multidisciplinary discussion (MDD) fail to yield a confident diagnosis. In these cases, histology may be necessary. Transbronchial lung cryobiopsy (TBLC) is a bronchoscopic procedure that has been developed in recent years and currently contributes to diagnostic work-up in patients with ILD. TBLC provides tissue samples for histological analysis with an acceptable risk of complications, consisting mainly in pneumothorax or bleeding. In addition to higher diagnostic yield than conventional forceps biopsies, the procedure shows a better safety profile than surgical biopsies. The indication to perform TBLC is decided during a 1st MDD and during a 2nd MDD, results can provide a diagnostic yield approximating 80%. TBLC appears to be an attractive, minimally invasive technique to be proposed as a first-line procedure in selected patients in experienced centers, while surgical lung biopsy may be considered as a second-line solution.

Further investigation of lead exposure as a potential threatening process for a scavenging marsupial species.

There is a growing recognition of the harmful effects of lead exposure on avian and mammalian scavengers. This can lead to both lethal and non-lethal effects which may negatively impact wildlife populations. Our objective was to assess medium-term lead exposure in wild Tasmanian devils (Sarcophilus harrisii). Frozen liver samples (n = 41), opportunistically collected in 2017-2022, were analysed using inductively coupled plasma mass spectrometry (ICP-MS) to determine liver lead concentrations. These results were then used to calculate the proportion of animals with elevated lead levels (>5 mg/kg dry weight) and examine the role of explanatory variables that may have influenced the results. The majority of samples analysed were from the south-east corner of Tasmania, within 50 km of Hobart. No Tasmanian devil samples were found to have elevated lead levels. The median liver lead concentration was 0.17 mg/kg (range 0.05-1.32 mg/kg). Female devils were found to have significantly higher liver lead concentrations than males (P = 0.013), which was likely related to lactation, but other variables (age, location, body mass) were not significant. These results suggest that wild Tasmanian devil populations currently show minimal medium-term evidence of exposure to lead pollution, although samples were concentrated in peri-urban areas. The results provide a baseline level which can be used to assess the impact of any future changes in lead use in Tasmania. Furthermore, these data can be used as a comparison for lead exposure studies in other mammalian scavengers, including other carnivorous marsupial species.

Vetting of medical imaging referrals: A scoping review of the radiographers' role.

INTRODUCTION: Vetting and treatment verification, are now an expectation of threshold radiography competencies at qualification. Radiographer-led vetting contributes to the expedition of patients' treatment and management. However, the current state and the role of the radiographer in vetting medical imaging referrals remains unclear. This review aims to explore the current state and associated challenges to a radiographer-led vetting and offer directions for future research by addressing knowledge gaps. METHOD: The Arksey and O'Malley methodological framework was employed for this review. This includes a comprehensive search using key terms relating to radiographer-led vetting across relevant databases: Medline, PubMed, AMED and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Articles were screened for eligibility and information extracted and analysed descriptively to map the available evidence. RESULTS: 1149 studies were identified with 12 articles included for this review after duplicates were removed. The findings indicate existence of some radiographer-led vetting activities in practice; however, the scope of this practice is associated with a large variance across settings. Key challenges relating to radiographer-led vetting include referral selectivity, medical professional dominance, and lack of clinical indication on referrals. CONCLUSION: Radiographers vet various categories of referrals depending on jurisdictional policies and more clarity in regulation, advanced practice training and change in workplace culture is needed to support radiographer-led vetting. IMPLICATION FOR PRACTICE: Radiographer-led vetting should be championed across settings through formalised training to widen the scope of advance practice and career progression pathways for radiographers as a means of ensuring optimal use of resources.

The role of outpatient needle arthroscopy in the diagnosis and management of musculoskeletal complaints: A systematic review of the Arthrex NanoScope.

BACKGROUND: The aim was to review the literature regarding needle arthroscopy using the Arthrex NanoScope system and evaluate: (1) the diagnostic indications, utility, and efficacy compared to conventional methods, and (2) the therapeutic indications, safety, and reported outcomes. METHODS: Searches of three databases (MEDLINE, Embase and PubMed) were conducted in November 2021 using MeSH terms: 'needle arthroscopy', 'human', 'in office arthroscopy', 'needle arthroscope', 'nanoscopic', 'surgery', 'nanoscope' and 'percutaneous arthroscopy'. The included studies were catalogued, quality-assessed using Methodological Index for Non-Randomised Studies (MINORS), and analysed using the Cochrane data collection templates for randomised control trials (RCT) and non-randomised control trials (non-RCT). The majority of studies were non-numerical and were examined using qualitative analysis. RESULTS: The search yielded 314 studies, 22 of which were included for analysis. MINORS assessment was applicable to four studies. Mean MINORS was 10.7/16 with the most frequent limitations being lack of unbiased endpoint or sample size calculation. The level of evidence ranged from level IV-V. Diagnostic and therapeutic indications were described in relation to the: knee (n = 10); shoulder (n = 6); foot/ankle (n = 3); elbow (n = 2), and miscellaneous (n = 1). CONCLUSIONS: Needle arthroscopy can augment the diagnostic process in patients presenting with musculoskeletal complaints, and may provide benefits in terms of diagnostic accuracy, cost efficiency, timeliness of investigation, and a visually impactful patient-centred consultation. Therapeutic interventions are reported by a small number of pioneer groups who report some benefits over conventional arthroscopy. The available literature remains small and of low quality, and more evidence is needed with regards to patient selection, efficacy, safety, and cost. LEVEL OF EVIDENCE: Level V (based on the weakest study included in the Systematic Review).

A single-arm, multicenter, phase II trial of osimertinib in patients with epidermal growth factor receptor exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations.

BACKGROUND: For patients with stage IV non-small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R mutations, osimertinib is the standard of care. Investigating the activity and safety of osimertinib in patients with EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations is of clinical interest. PATIENTS AND METHODS: Patients with stage IV non-small-cell lung cancer with confirmed EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations were eligible. Patients were required to have measurable disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients were required to be EGFR tyrosine kinase inhibitor-naive. The primary objective was objective response rate, and secondary objectives were progression-free survival, safety, and overall survival. The study used a two-stage design with a plan to enroll 17 patients in the first stage, and the study was terminated after the first stage due to slow accrual. RESULTS: Between May 2018 and March 2020, 17 patients were enrolled and received study therapy. The median age of patients was 70 years (interquartile range 62-76), the majority were female (n = 11), had a performance status of 1 (n = 10), and five patients had brain metastases at baseline. The objective response rate was 47% [95% confidence interval (CI) 23% to 72%], and the radiographic responses observed were partial response (n = 8), stable disease (n = 8), and progressive disease (n = 1). The median progression-free survival was 10.5 months (95% CI 5.0-15.2 months), and the median OS was 13.8 months (95% CI 7.3-29.2 months). The median duration on treatment was 6.1 months (range 3.6-11.9 months), and the most common adverse events (regardless of attribution) were diarrhea, fatigue, anorexia, weight loss, and dyspnea. CONCLUSIONS: This trial suggests osimertinib has activity in patients with these uncommon EGFR mutations.

Moving orthopaedic procedures out of the operating theatre:Outpatient needle arthroscopy can reduce cost & waste, and increase inpatient capacity compared to conventional knee arthroscopy.

BACKGROUND: Needle arthroscopy (NA) is an emerging technique that could streamline pathways, facilitate timely care, and reduce service burden. The primary aim was to assess the practical and economic viability of an outpatient NA service. Secondary aims were to assess the relative costs and benefits compared to a conventional arthroscopy (CA) service. METHODS: This service feasibility study was conducted between 2021-2022 in a high-volume national treatment centre. A NA pathway was established for patients with chronic soft tissue pathology or early degenerative knee disease. The pathway was evaluated in terms of: i) cost; ii) efficiency, and iii) waste production, and an assessment was conducted of the patient-related and service-related effects. RESULTS: The cost of the NA pathway was £1555.20 per patient, compared to £2,351.53 for CA. Time to management was 45 days for NA versus 180 days for CA. The NA pathway involved two hospital attendances, whereas CA required a minimum of three. NA cases produced 1.4 kg of non-recyclable waste compared to 5.0 kg produced by CA. For every two cases managed by NA instead of CA, capacity for one additional obligate-inpatient procedure was created. CONCLUSIONS: The NA pathway offers a technically and economically viable approach for the management of refractory knee symptoms in the context of chronic soft tissue or early degenerative disease. NA placed less demand on hospital resources, produced two-thirds less non-recyclable waste, and is amenable to a one-stop clinic approach. Clinical studies focused on objective and patient-reported outcome measures are required to assess clinical efficacy.

Inpatient target discharge weight for early-onset anorexia nervosa: Restoring premorbid BMI percentile to improve height prognosis.

OBJECTIVE: Early-onset anorexia nervosa (EO-AN) is characterized by restricted food intake leading to low body weight, emerging before 14 years old. Most patients reaching a target body mass index (BMI) around the 25th percentile at hospitalization discharge display an incomplete prospective height catch-up. A better understanding of height prognosis determinants is required. METHODS: In 74 children with an EO-AN, we collected height and weight premorbidly, at hospitalization, and at discharge, 6 months, 12 months, and at longer-term follow-up of 36 months. We defined a height prognosis parameter (HPP) as the difference between the height percentile at follow-up times and the premorbid height percentile. We explored the relationship between weight parameters and height catch-up at follow-up with linear regression analyses. RESULTS: A higher weight suppression (WS) - i.e., difference between premorbid and current BMI - at admission and discharge was associated with lower HPP - i.e., a greater loss of height - at 12 months and 36 months follow-up. Similarly, a higher premorbid BMI percentile was associated with a lower HPP at 12 and 36 months. CONCLUSION: Target discharge weight for EO-AN patients should be tailored and based on premorbid BMI trajectory to improve height prognosis.

A mechanistic physiologically based model to assess the effect of study design and modified physiology on formulation safe space for virtual bioequivalence of dermatological drug products.

Physiologically based pharmacokinetic (PBPK) models are widely accepted tools utilised to describe and predict drug pharmacokinetics (PK). This includes the use of dermal PBPK models at the regulatory level including virtual bioequivalence (VBE) studies. The current work considers the Topicort® Spray formulation, which contains 0.25% desoximetasone (DSM), as an example formulation. Quantitative formulation composition and in vitro permeation testing (IVPT) data were obtained from the public literature to develop a mechanistic model using the multi-phase, multi-layer (MPML) MechDermA IVPT module in the Simcyp Simulator. In vitro-in vivo extrapolation functionality was used to simulate in vivo PK for various scenarios and predict a 'safe space' for formulation bioequivalence using the VBE module. The potential effect of vasoconstriction, impaired barrier function, and various dosing scenarios on the formulation safe space was also assessed. The model predicted 'safe space' for formulation solubility suggesting that a 50% change in solubility may cause bio-in-equivalence, whereas viscosity could deviate by orders of magnitude and the formulation may still remain bioequivalent. Evaporation rate and fraction of volatile components showed some sensitivity, suggesting that large changes in the volume or composition of the volatile fraction could cause bio-in-equivalence. The tested dosing scenarios showed decreased sensitivity for all formulation parameters with a decreased dose. The relative formulation bioequivalence was insensitive to vasoconstriction, but the safe space became wider with decreased barrier function for all parameters, except viscosity that was unaffected.

Do you know when the inhaler is empty?

BACKGROUND: Medication review is recommended at asthma appointments. The presence of propellant in the metered dose inhalers (MDIs) makes it challenging to identify when the inhaler is empty. The COVID-19 pandemic has resulted in move towards more virtual monitoring of care. We aimed to evaluate if patients identify when the inhaler is empty and the method of inhaler disposal. METHODS: Prospective, multicentre quality improvement project. Data collected from children with asthma and other respiratory conditions. OUTCOME MEASURES: Children/carers attending hospital were asked how they identify an empty salbutamol inhaler; dose counters in the preventer inhalers and disposal practices were reviewed. RESULTS: 157 patients recruited. 125 (73.5%) patients deemed an empty inhaler as either full/partially full. 12 of 66 (18.2%) preventer inhalers with a dose counter were empty. 83% disposed their inhalers in a dustbin. CONCLUSIONS: Patients cannot reliably identify when their MDI is empty. There is an urgent need for improving inhaler technology and providing appropriate guidance on how to identify when an MDI is empty.

Valley Splitting in Silicon from the Interference Pattern of Quantum Oscillations.

We determine the energy splitting of the conduction-band valleys in two-dimensional electrons confined in silicon metal oxide semiconductor Hall-bar transistors. These silicon metal oxide semiconductor Hall bars are made by advanced semiconductor manufacturing on 300 mm silicon wafers and support a two-dimensional electron gas of high quality with a maximum mobility of 17.6×10^{3} cm^{2}/Vs and minimum percolation density of 3.45×10^{10} cm^{-2}. Because of the low disorder, we observe beatings in the Shubnikov-de Haas oscillations that arise from the energy splitting of the two low-lying conduction band valleys. From the analysis of the oscillations beating patterns up to T=1.7 K, we estimate a maximum valley splitting of ΔE_{VS}=8.2 meV at a density of 6.8×10^{12} cm^{-2}. Furthermore, the valley splitting increases with density at a rate consistent with theoretical predictions for a near-ideal semiconductor-oxide interface.

Trends and associated factors for Covid-19 hospitalisation and fatality risk in 2.3 million adults in England.

The Covid-19 mortality rate varies between countries and over time but the extent to which this is explained by the underlying risk in those infected is unclear. Using data on all adults in England with a positive Covid-19 test between 1st October 2020 and 30th April 2021 linked to clinical records, we examined trends and risk factors for hospital admission and mortality. Of 2,311,282 people included in the study, 164,046 (7.1%) were admitted and 53,156 (2.3%) died within 28 days of a positive Covid-19 test. We found significant variation in the case hospitalisation and mortality risk over time, which remained after accounting for the underlying risk of those infected. Older age groups, males, those resident in areas of greater socioeconomic deprivation, and those with obesity had higher odds of admission and death. People with severe mental illness and learning disability had the highest odds of admission and death. Our findings highlight both the role of external factors in Covid-19 admission and mortality risk and the need for more proactive care in the most vulnerable groups.

SPEDE-sampler: An R Shiny application to assess how methodological choices and taxon sampling can affect Generalized Mixed Yule Coalescent output and interpretation.

Species delimitation tools are vital to taxonomy and the discovery of new species. These tools can make use of genetic data to estimate species boundaries, where one of the most widely used methods is the Generalized Mixed Yule Coalescent (GMYC) model. Despite its popularity, a number of factors are known to influence the performance and resulting inferences of the GMYC. Moreover, the few studies that have assessed model performance to date have been predominantly based on simulated data sets, where model assumptions are not violated. Here, we present a user-friendly R Shiny application, 'SPEDE-sampler' (SPEcies DElimitation sampler), that assesses the effect of computational and methodological choices, in combination with sampling effects, on the GMYC model. Output phylogenies are used to test the effect that (1) sample size, (2) BEAST and GMYC parameters (e.g. prior settings, single vs multiple threshold, clock model), and (3) singletons have on GMYC output. Optional predefined grouping information (e.g. morphospecies/ecotypes) can be uploaded in order to compare it with GMYC species and estimate percentage match scores. Additionally, predefined groups that contribute to inflated species richness estimates are identified by SPEDE-sampler, allowing for the further investigation of potential cryptic species or geographical substructuring in those groups. Merging by the GMYC is also recorded to identify where traditional taxonomy has overestimated species numbers. Four worked examples are provided to illustrate the functionality of the program's workflow, and the variation that can arise when applying the GMYC model to empirical data sets. The R Shiny program is available for download at https://github.com/clarkevansteenderen/spede_sampler_R.

Non-Gaussian Mechanical Motion via Single and Multiphonon Subtraction from a Thermal State.

Quantum optical measurement techniques offer a rich avenue for quantum control of mechanical oscillators via cavity optomechanics. In particular, a powerful yet little explored combination utilizes optical measurements to perform heralded non-Gaussian mechanical state preparation followed by tomography to determine the mechanical phase-space distribution. Here, we experimentally perform heralded single-phonon and multiphonon subtraction via photon counting to a laser-cooled mechanical thermal state with a Brillouin optomechanical system at room temperature and use optical heterodyne detection to measure the s-parametrized Wigner distribution of the non-Gaussian mechanical states generated. The techniques developed here advance the state of the art for optics-based tomography of mechanical states and will be useful for a broad range of applied and fundamental studies that utilize mechanical quantum-state engineering and tomography.

Breast cancer detection: Comparison of digital mammography and digital breast tomosynthesis across non-dense and dense breasts.

INTRODUCTION: Breast density is associated with an increase in breast cancer risk and limits early detection of the disease. This study assesses the diagnostic performance of mammogram readers in digital mammography (DM) and digital breast tomosynthesis (DBT). METHODS: Eleven breast readers with 1-39 years of experience reading mammograms and 0-4 years of experience reading DBT participated in the study. All readers independently interpreted 60 DM cases (40 normal/20 abnormal) and 35 DBT cases (20 normal/15 abnormal). Sensitivity, specificity, ROC AUC, and diagnostic confidence were calculated and compared between DM and DBT. RESULTS: DBT significantly improved diagnostic confidence in both dense breasts (p = 0.03) and non-dense breasts (p = 0.003) but not in other diagnostic performance metrics. Specificity was higher in DM for readers with >7 years' experience (p = 0.03) in reading mammography, non-radiologists (p = 0.04), readers who had completed a 3-6 months training fellowship in breast imaging (p = 0.04), and those with ≤2 years' experience in reading DBT (p = 0.02), particularly in non-dense breasts. CONCLUSION: Diagnostic confidence was higher in DBT when compared to DM. In contrast, other performance metrics appeared to be similar or better with DM and may be influenced by the lack of experience of the reader cohort in reading DBT. IMPLICATIONS FOR PRACTICE: The benefits of DBT may not be entirely accrued until radiologists attain expertise in DBT interpretation. Specificity of DBT varied according to reader characteristics, and these characteristics may be useful for optimising pairing strategies in independent double reading of DBT as practiced in Australia to reduce false positive diagnostic errors.

Underwater noise from submarine turbidity currents.

Noise from turbidity currents flowing down the face of a fjord delta was measured underwater at frequencies from 1 to 1200 kHz. The noise spectra are consistent with sound generation by collisions among sand-sized particles. The spectra from the leading head extend to higher frequencies than those from the trailing body, indicating that collisions were between finer-grained particles in the head and coarser-grained particles in the body. Noise intensity increased 100-fold for a two-fold increase in head speed, consistent with the expected collision rate for granular materials in the high-flow gas-like phase and highly turbulent particle-laden flows.