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Background: Roughly 10% of children aged 3 -17 in the USA are diagnosed with attention-deficit hyperactivity disorder (ADHD), and minorities are less likely to initiate common pharmacologic treatment. We conducted a review of the literature to examine meditation as a safe, effective, and low-cost alternative. Methods: We searched PubMed and other journals using "meditation," "mindfulness," "minority," related keywords, and relevant MeSH terms. Eligible studies involved racial/ethnic minorities in the USA, reported quantitative psychosocial outcomes, and were published in a peer-reviewed, English-language journal. Results: Out of 119 "hits," 111 were eliminated as duplicates or were not relevant. A full-text review of the remaining eight revealed that none fully met our eligibility criteria. Besides the obvious lack of studies, those reviewed reported incomplete demographic and clinical data. They also employed different and inconsistent research methodologies, interventions and modalities, and statistical analyses. This hindered understanding exactly which populations may benefit from meditation, and for which specific symptoms. Conclusion: We recommend a socio-ecological model in examining intervention modalities, especially in the context of intrapersonal, interpersonal, organizational, environmental, and policy domains. We also suggest the possible inclusion of research older than 10 years, conducted outside of the USA, on minority and non-minority populations, for supplementary and confirmatory data. We advocate for consistency in study design and data collection, which would help align research conducted in different countries. Searches should also include variations of meditation such as "mindfulness" and "guided imagery," and associated symptoms and comorbidities of ADHD, including "learning disorder" and "behavioral problems."

BackgroundFHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data. ObjectiveThis study aimed to design and implement a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making. MethodsA Python package for the use of multimodal FHIR data (FHIRPACK [FHIR Python Analysis Conversion Kit]) was developed and pioneered in 5 real-world clinical use cases, that is, myocardial infarction, stroke, diabetes, sepsis, and prostate cancer. Patients were identified based on the ICD-10 (International Classification of Diseases, Tenth Revision) codes, and outcomes were derived from laboratory tests, prescriptions, procedures, and diagnostic reports. Results were provided as browser-based dashboards. ResultsFor 2022, a total of 1,302,988 patient encounters were analyzed. (1) Myocardial infarction: in 72.7% (261/359) of cases, medication regimens fulfilled guideline recommendations. (2) Stroke: out of 1277 patients, 165 received thrombolysis and 108 thrombectomy. (3) Diabetes: in 443,866 serum glucose and 16,180 glycated hemoglobin A1c measurements from 35,494 unique patients, the prevalence of dysglycemic findings was 39% (13,887/35,494). Among those with dysglycemia, diagnosis was coded in 44.2% (6138/13,887) of the patients. (4) Sepsis: In 1803 patients, Staphylococcus epidermidis was the primarily isolated pathogen (773/2672, 28.9%) and piperacillin and tazobactam was the primarily prescribed antibiotic (593/1593, 37.2%). (5) PC: out of 54, three patients who received radical prostatectomy were identified as cases with prostate-specific antigen persistence or biochemical recurrence. ConclusionsLeveraging FHIR data through large-scale analytics can enhance health care quality and improve patient outcomes across 5 clinical specialties. We identified (1) patients with sepsis requiring less broad antibiotic therapy, (2) patients with myocardial infarction who could benefit from statin and antiplatelet therapy, (3) patients who had a stroke with longer than recommended times to intervention, (4) patients with hyperglycemia who could benefit from specialist referral, and (5) patients with PC with early increases in cancer markers.

Societal Impact Statement Refining circular multitrophic food production methods, which integrate plant, fish, and insect outputs, is imperative for environmental sustainability. Our findings suggest that the right protein choices in fish feed, like black soldier fly meal and poultry meal, can notably enhance the nutrient profile of fish waste water. This, in turn, is conducive for hydroponic cultivation, enhancing the nutritional attributes of plants like basil and lettuce. As we reduce environmental impact and optimize resource use, it is evident that our food ecosystems are deeply intertwined. Harnessing these synergies could redefine our approach to food production, paving the way for a more sustainable global future. Summary Optimization of nutrient use efficiencies in circular multitrophic food production systems (i.e., plant, fish, and insect production) is crucial for sustainability. This study tested how protein ingredient choice in fish feed influences the plant nutritional value of the fish waste water when used for hydroponic crop production. Waste water samples were obtained from recirculating aquaculture systems (RAS) in which Nile tilapia (Oreochromis niloticus) were fed different single protein source diets—black soldier fly meal (BSFM), poultry by‐product meal (PM), poultry blood meal (PBM), and fish meal. Water was analyzed for plant nutrients and used for lettuce and basil cultivation to evaluate their suitability for hydroponic crop production—viz. yield, mineral nutrient, and selected secondary metabolite levels. BSFM RAS water had the highest concentrations of K, Mg, and micronutrients (Cu, Mn, Mo, Zn) of the RAS waters, whereas PM RAS water contained the highest P concentration and had a mean pH of 6.5 closer to the optimum pH for hydroponic plants. These RAS waters consequently lead to the highest yields in basil and lettuce indicating the importance of the aforementioned factors. From a plant production perspective, BSFM appears promising as a protein source in fish feeds for aquaponics. Usage of RAS waters for plant production helps reduce (i) environmental impact of RAS water and (ii) resource input in plant production. Longer term RAS trials should be conducted to determine the maximum nutrient concentrations achievable during fish production with diets including BSFM as the main protein source.

The practical application of new single molecule protein sequencing (SMPS) technologies requires accurate estimates of their associated sequencing error rates. Here, we describe the development and application of two distinct parameter estimation methods for analyzing SMPS reads produced by fluorosequencing. A Hidden Markov Model (HMM) based approach, extends whatprot, where we previously used HMMs for SMPS peptide-read matching. This extension offers a principled approach for estimating key parameters for fluorosequencing experiments, including missed amino acid cleavages, dye loss, and peptide detachment. Specifically, we adapted the Baum-Welch algorithm, a standard technique to estimate transition probabilities for an HMM using expectation maximization, but modified here to estimate a small number of parameter values directly rather than estimating every transition probability independently. We demonstrate a high degree of accuracy on simulated data, but on experimental datasets, we observed that the model needed to be augmented with an additional error type, N-terminal blocking. This, in combination with data pre-processing, results in reasonable parameterizations of experimental datasets that agree with controlled experimental perturbations. A second independent implementation using a hybrid of DIRECT and Powell's method to reduce the root mean squared error (RMSE) between simulations and the real dataset was also developed. We compare these methods on both simulated and real data, finding that our Baum-Welch based approach outperforms DIRECT and Powell's method by most, but not all, criteria. Although some discrepancies between the results exist, we also find that both approaches provide similar error rate estimates from experimental single molecule fluorosequencing datasets.

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Abstract Introduction Patients living in rural areas have worse cancer‐specific outcomes. This study examines the effect of family‐based social capital on genitourinary cancer survival. We hypothesized that rural patients with urban relatives have improved survival relative to rural patients without urban family. Methods We examined rural and urban based Utah individuals diagnosed with genitourinary cancers between 1968 and 2018. Familial networks were determined using the Utah Population Database. Patients and relatives were classified as rural or urban based on 2010 rural–urban commuting area codes. Overall survival was analyzed using Cox proportional hazards models. Results We identified 24,746 patients with genitourinary cancer with a median follow‐up of 8.72 years. Rural cancer patients without an urban relative had the worst outcomes with cancer‐specific survival hazard ratios (HRs) at 5 and 10 years of 1.33 (95% CI 1.10–1.62) and 1.46 (95% CI 1.24–1.73), respectively relative to urban patients. Rural patients with urban first‐degree relatives had improved survival with 5‐ and 10‐year survival HRs of 1.21 (95% CI 1.06–1.40) and 1.16 (95% CI 1.03–1.31), respectively. Conclusions Our findings suggest rural patients who have been diagnosed with a genitourinary cancer have improved survival when having relatives in urban centers relative to rural patients without urban relatives. Further research is needed to better understand the mechanisms through which having an urban family member contributes to improved cancer outcomes for rural patients. Better characterization of this affect may help inform policies to reduce urban–rural cancer disparities.

We present SN 2023zaw—a subluminous ( M _r = −16.7 mag) and rapidly evolving supernova ( t _1/2, _r = 4.9 days), with the lowest nickel mass (≈0.002 M _⊙ ) measured among all stripped-envelope supernovae discovered to date. The photospheric spectra are dominated by broad He i and Ca near-infrared emission lines with velocities of ∼10,000−12,000 km s ^−1 . The late-time spectra show prominent narrow He i emission lines at ∼1000 km s ^−1 , indicative of interaction with He-rich circumstellar material. SN 2023zaw is located in the spiral arm of a star-forming galaxy. We perform radiation-hydrodynamical and analytical modeling of the lightcurve by fitting with a combination of shock-cooling emission and nickel decay. The progenitor has a best-fit envelope mass of ≈0.2 M _☉ and an envelope radius of ≈50 R _⊙ . The extremely low nickel mass and low ejecta mass (≈0.5 M _⊙ ) suggest an ultrastripped SN, which originates from a mass-losing low-mass He-star (zero-age main-sequence mass < 10 M _⊙ ) in a close binary system. This is a channel to form double neutron star systems, whose merger is detectable with LIGO. SN 2023zaw underscores the existence of a previously undiscovered population of extremely low nickel mass (

AbstractWith rising therapeutic use worldwide, prescription stimulants are increasingly implicated in poisonings. Most of the limited research on stimulant poisoning focuses on illicit amphetamines. We aimed to investigate the clinical effects of intentional prescription stimulant poisoning. This is a retrospective review of hospitalised patients referred to a Poisons Information Centre and a toxicology unit following intentional exposures to prescription stimulants (dexamfetamine, lisdexamfetamine and methylphenidate) from 1 January 2018 through 31 December 2021. Patients were identified from both units’ databases and data extracted from medical records. To facilitate comparison a dexamfetamine-equivalent dose was calculated. There were 186 intentional exposures in 178 patients (median age 17 years, males 54%) over the study period, consisting of 44 (24%) dexamfetamine, 50 (27%) lisdexamfetamine and 92 (49%) methylphenidate exposures. Stimulant exposures rose annually from 34 presentations in 2018 to 61 in 2021. Deliberate self-poisoning accounted for 139 (75%) presentations and the remaining 47 (25%) were recreational. Co-ingestions were taken in 101 (54%) presentations, leaving 85 (46%) single-agent exposures with a median dexamfetamine-equivalent dose ingested of 135 mg (range 15-4500 mg). Of the single-agent exposures tachycardia (69%), hypertension (47%) and agitation (58%) were the commonest clinical features. Most patients (58%) had mild-moderate symptoms, managed solely with supportive cares or oral sedation. Twenty-three (27%) patients had severe agitation receiving parenteral sedation. Rhabdomyolysis occurred in 3 single-agent exposures (4%) and 8 (9%) had an acute kidney injury. Severe cardiovascular toxicity was rare, with one patient developing hypertensive crisis and another having a supraventricular tachycardia. The median length of stay for single-agent exposures was 11 h (IQR 5-19 h). Prescription stimulant poisoning appears to be rising and commonly results in tachycardia, hypertension, and agitation. Severe cardiovascular toxicity was rare.

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

Peer To Peer (P2P) Lending is the result of the development of digital technology which is a solution for people who need funds quickly without having to go through convoluted procedures such as banking institutions. In P2P lending activities, there are several parties, namely Lenders, Organizing Companies, and Borrowers who are related to law. Based on POJK Number 77/POJK.01/2016 concerning Information Technology-Based Borrowing and Borrowing Services, in P2P Lending there are two kinds of legal relationships, one of which is the legal relationship between the Lender and the P2P Lending Company as outlined in the Electronic Loan Distribution Contract. In making the contract, the application of the principle of balance is important in order to create balance for the parties to the contract. This research uses a descriptive normative legal research method. Secondary data in the form of primary, secondary and tertiary legal materials were collected using library research techniques. Data analysis was performed using qualitative data analysis methods. The study results shows that the Electronic Loan Distribution Contract Number PPP/PID/2021/07/Lending Transaction TD29585580030360 between Lenders and P2P lending companies does not fulfill the overall balance principle. It was found after looking at the three aspects used as test factors for the application of the principle of balance in the form of the actions of the parties, the contents of the contract, and the execution of the contract. The principle of balance is met in the first (actions of the parties) and third (execution of the contract) aspects. Regarding the second aspect, namely the contents of the contract, the author finds that the principle of balance has not been fully implemented, because the contract is in a standard form made unilaterally by a P2P lending company for Lenders. Failure to apply the principle of balance in a contract can result in the contract becoming null and voidable or null and void.

Abstract Background Malnutrition has various adverse effects in children. This study aimed to determine risk factors for malnutrition among hospitalised children, changes in nutritional status at admission and discharge and effects of use of systematic anthropometric measurement in identification of malnutrition. Methods We enrolled 426 children, aged between 6 months and 15 years, admitted to Siddhi Memorial Hospital, Bhaktapur, Nepal, from November 2016 to June 2017. Anthropometric measurements were performed at the time of admission and discharge. Risk factors were assessed by multivariable logistic regression models. Results Median age of children was 26 months (IQR: 13–49), and males were 58.7%. The prevalence of wasting was 9.2% (39/426) at admission and 8.5% (36/426) at discharge. Risk factors associated with wasting at admission were ethnic minority (aOR: 3.6, 95% CI 1.2–10.8), diarrhoeal diseases (aOR = 4.0; 95% CI 1.3–11.8), respiratory diseases (aOR: 3.4, 95% CI 1.4–8.1) and earthquake damage to house (aOR = 2.6; 95% CI 1.1–6.3). Clinical observation by care providers identified only 2 out of 112 malnutrition cases at admission and 4 out of 119 cases at discharge that were detected by the systematic anthropometric measurement. Conclusions Ethnic minority, diarrhoeal diseases, respiratory infections and house damage due to the earthquake were risk factors associated with wasting. Systematic anthropometric examination can identify significantly more malnourished children than simple observation of care providers.

Specific heat at constant pressure is traditionally a difficult thermodynamic quantity to obtain from first-principles calculations. While theoretical avenues to Cp(T) do exist—most notably, the quasi-harmonic approximation—there are many materials for which this approximation is not valid. One of those materials is Ge. In this paper, we demonstrate how a new method—termed the Beyond Quasi-Harmonic method—takes into account all anharmonic vibrations by showing how our results are significantly better than those achieved through using the quasi-harmonic model. In addition, we calculate Cp(T) for 3C-SiC, a material for which there are surprisingly few experimental results. For 3C-SiC, our results agree well with the available experiments, and for Ge, our results agree very well with the generally accepted values.

The haptic impression of textile surface properties has a decisive influence on its evaluation and ultimately on its acceptance and usability. Many solutions are used to replicate a static contour or shape, e.g. to feel controls on common touch displays. In contrast, this project investigates whether it is possible to simulate the roughness or friction behaviour of a textile surface using a commercially available mobile device.

Abstract Purpose The purpose of this study was to review our institutional experience with the EOS machine in order to identify the incidence and clinical significance of incidental extraspinal findings (IESF) in an adult spinal deformity population. Methods Our institutional database was queried for all full-length standing radiographs generated by the EOS machine. Dictations were reviewed and the number of incidental extraspinal findings were classified using a previously described system. All findings related to the spine were excluded. A subset of electronic medical records were reviewed to determine further workup for individual findings of suspected clinical significance. Results Original database query based on radiology reports returned a total of 1857 EOS studies. Duplicate studies, studies without the entire body, and patients with more than 1 study during the search period were excluded. 503 patient studies (55.5% female, mean age 59-years-old, range 18 to 91-years-old) met inclusion criteria. The overall rate of incidental extraspinal findings in our study was 60.4% (304 findings in 503 patients). Most findings were classified as Minor. The rate of Major and Moderate findings was 4.8%. The final rate of clinically significant incidental extraspinal findings was 0.8% and included 3 presumed metastatic lesions in long bones and 1 pulmonary nodule. Conclusion To our knowledge this is the first study that reports the rate of incidental extraspinal findings on full body EOS studies. We report a low rate (0.8%) of clinically significant incidental extraspinal findings which is lower than that of CT or MRI. Further research is warranted in comparing EOS and standard radiography.

Abstract Background This paper describes a model for estimating COVID-19 related excess deaths that are a direct consequence of insufficient hospital ward bed and intensive care unit (ICU) capacity. Methods Compartmental models were used to estimate deaths under different combinations of ICU and ward care required and received in England up to late April 2021. Model parameters were sourced from publicly available government information and organisations collating COVID-19 data. A sub-model was used to estimate the mortality scalars that represent increased mortality due to insufficient ICU or general ward bed capacity. Three illustrative scenarios for admissions numbers, ‘Optimistic’, ‘Middling’ and ‘Pessimistic’, were modelled and compared with the subsequent observations to the 3rd February. Results The key output was the demand and capacity model described. There were no excess deaths from a lack of capacity in the ‘Optimistic’ scenario. Several of the ‘Middling’ scenario applications resulted in excess deaths—up to 597 deaths (0.6% increase) with a 20% reduction compared to best estimate ICU capacity. All the ‘Pessimistic’ scenario applications resulted in excess deaths, ranging from 49,178 (17.0% increase) for a 20% increase in ward bed availability, to 103,735 (35.8% increase) for a 20% shortfall in ward bed availability. These scenarios took no account of the emergence of the new, more transmissible, variant of concern (b.1.1.7). Conclusions Mortality is increased when hospital demand exceeds available capacity. No excess deaths from breaching capacity would be expected under the ‘Optimistic’ scenario. The ‘Middling’ scenario could result in some excess deaths—up to a 0.7% increase relative to the total number of deaths. The ‘Pessimistic’ scenario would have resulted in significant excess deaths. Our sensitivity analysis indicated a range between 49,178 (17% increase) and 103,735 (35.8% increase). Given the new variant, the pessimistic scenario appeared increasingly likely and could have resulted in a substantial increase in the number of COVID-19 deaths. In the event, it would appear that capacity was not breached at any stage at a national level with no excess deaths. it will remain unclear if minor local capacity breaches resulted in any small number of excess deaths.

The recent discovery of enormous Ly α nebulae (ELANe), characterized by physical extents >200 kpc and Ly α luminosities >10 ^44 erg s ^−1 , provides a unique opportunity to study the intergalactic medium and circumgalactic medium in distant galaxies. Many existing ELANe detections are associated with local overdensities of active galactic nuclei (AGN). We have initiated a search for ELANe around regions containing pairs of quasi-stellar objects (QSOs) using the Palomar Cosmic Web Imager. The first study of this search, Cai et al., presented results of ELAN0101+0201, which was associated with a QSO pair at z = 2.45. In this study, all targets residing in QSO pair environments analyzed have Ly α detections, but only one of the four targets meets the classification criteria of an ELANe associated with a QSO pair region ( z ∼ 2.87). The other three sample detections of Ly α nebulae do not meet the size and luminosity criteria to be classified as ELANe. We find kinematic evidence that the ELANe J1613 is possibly powered mostly by AGN outflows. The analysis of circularly averaged surface brightness profiles of emission from the Ly α regions shows that the Ly α emission around z ∼ 2 QSO pairs is consistent with emission around individual QSOs at z ∼ 2, which is fainter than that around z ∼ 3 QSOs. A larger sample of Ly α at z ∼ 2 will be needed to determine if there is evidence of redshift evolution when compared to nebular emissions at z ∼ 3 from other studies.

The eustachian valve is an uncommon embryologic remnant of the sinus venosus present in the right atrium that may persist in some adults. Typically, in adults, right sided valvular endocarditis is associated with intravenous drug use or presence of central venous of hemodialysis catheters. Eustachian valve endocarditis is a rare cause of right sided endocarditis with very few cases reported. A routine transthoracic echocardiogram (TTE) may not be sensitive and miss this infection. Pasteurella multocida is gram negative microorganism that can rarely cause infective endocarditis. We present what we believe to be the first reported case of Eustachian valve endocarditis (EVE) caused by P. multocida.

Introduction BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysis This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and dissemination Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registration ClinicalTrials.gov NCT04327206

The Professional Doctorate in Education (EdD) is a doctoral level professional qualification for practising teachers that affords the opportunity to research an area of practice of particular interest. Many EdD students encounter mixed feelings, emotions and new identities as many could be leaders within their employment and seen as ‘experts’ in their role, however, they may find themselves on the periphery of a new community of which they are yet to feel a part. This reflective paper explores the role of ‘identity’ and ‘belonging’ in Professional Doctoral students with particular emphasis placed on situated learning theory (Lave & Wenger, 1991) and the notion of communities of practice. I discuss the idea of ‘identity congruence’ and how I experienced this in terms of my identity as a leader of learning and as a fledgling doctoral researcher. The paper concludes that communities of practice promote a sense of community and belonging that have clearly supported me through the doctoral journey.

Merkel cell carcinoma (MCC) is a highly aggressive non-melanoma skin cancer of the elderly which is associated with the Merkel cell polyomavirus (MCPyV). MCC reveals a trilinear differentiation characterized by neuroendocrine, epithelial and pre/pro B-cell lymphocytic gene expression disguising the cellular origin of MCC. Here we investigated the expression of the neuroendocrine key regulators RE1 silencing transcription factor (REST), neurogenic differentiation 1 (NeuroD1) and the Achaete-scute homolog 1 (ASCL1) in MCC. All MCCs were devoid of REST and were positive for NeuroD1 expression. Only one MCC tissue revealed focal ASCL1 expression. This was confirmed in MCPyV-positive MCC cell lines. Of interest, MCPyV-negative cell lines did express REST. The introduction of REST expression in REST-negative, MCPyV-positive MCC cells downregulated the neuroendocrine gene expression. The lack of the neuroendocrine master regulator ASCL1 in almost all tested MCCs points to an important role of the absence of the negative regulator REST towards the MCC neuroendocrine phenotype. This is underlined by the expression of the REST-regulated microRNAs miR-9/9* in REST-negative MCC cell lines. These data might provide the basis for the understanding of neuroendocrine gene expression profile which is expected to help to elucidate the cellular origin of MCC.

The ketogenic diet (KD) may have a role in treating super-refractory status epilepticus (SRSE). Predominantly used in paediatric epilepsy, there are few reports of its use in adults. We describe a 19-year-old man with UBE2A deficiency syndrome, drug resistant generalized epilepsy, and severe intellectual disability, who developed SRSE. Initiation of the KD on day 81 of his intensive care unit stay and achieving a state of ketosis seven days later resulted in SRSE resolution and discharge from hospital and recovery to his normal cognitive state. Initiating the KD required a multidisciplinary team for diet initiation and carer education. The KD requires a prospective study of efficacy for SRSE and this should include adult patients.

Dentistry is confronted with the functional and aesthetic consequences that result from an increased prevalence of misaligned and discrepant dental occlusal relations in modern industrialised societies. Previous studies have indicated that a reduction in jaw size in response to softer and more heavily processed foods during and following the Industrial Revolution (1,700 CE to present) was an important factor in increased levels of poor dental occlusion. The functional demands placed on the masticatory system play a crucial role in jaw ontogenetic development; however, the way in which chewing behaviours changed in response to the consumption of softer foods during this period remains poorly understood. Here we show that eating more heavily processed food has radically transformed occlusal power stroke kinematics. Results of virtual 3D analysis of the dental macrowear patterns of molars in 104 individuals dating to the Industrial Revolution (1,700-1,900 CE), and 130 of their medieval and early post-medieval antecedents (1,100-1,700 CE) revealed changes in masticatory behaviour that occurred during the early stages of the transition towards eating more heavily processed foods. The industrial-era groups examined chewed with a reduced transverse component of jaw movement. These results show a diminished sequence of occlusal contacts indicating that a dental revolution has taken place in modern times, involving a dramatic shift in the way in which teeth occlude and wear during mastication. Molar macrowear suggests a close connection between progressive changes in chewing since the industrialization of food production and an increase in the prevalence of poor dental occlusion in modern societies.

ABSTRACT: Objective: Fetal hyperthyroidism is a rare yet potentially fatal complication of past or present maternal Graves disease (GD). Our objective was to present a unique case of fetal hyperthyroidism in a mother with a prior history of GD and a cytochrome P450 2D6 (CYP2D6) polymorphism. Methods: The clinical course in addition to serial laboratory and imaging results are presented. These include thyroid-stimulating hormone, free thyroxine, and thyrotropin receptor antibody levels, as well as fetal ultrasound, doppler fetal heart rate, and cordocentesis testing. Results: A 27-year-old with a history of GD previously treated with radioiodine and a known cytochrome P450 polymorphism was referred to an endocrinology clinic at 17 weeks gestation for evaluation and management of fetal thyrotoxicosis. Despite close follow-up with a multidisciplinary care team and an aggressive “block and replace” treatment approach, progressive disease resulted in intrauterine fetal demise at 28 weeks gestation. Conclusion: To our knowledge, this is the first published case report of fetal hyperthyroidism accompanied by a maternal CYP2D6 polymorphism. We hypothesize that the maternal CYP2D6 poor metabolizer phenotype prevents formation of antithyroid drug (ATD) metabolites and thus decreases the efficacy of ATD treatment. We suggest this as an area of future research.

Quetiapine is occasionally associated with cardiovascular adverse effects such as QTc prolongation. QTc prolongation is a side effect that requires monitoring in order to avoid more serious cardiac complications. One particular understudied area is the potential for antipsychotics to elicit electroconduction abnormalities in patients with Wolff-Parkinson-White (WPW) Syndrome. In the present report, we describe a case of quetiapine overdose in a patient with WPW.

International frameworks for climate mitigation that build from national actions have been developed under the United National Framework Convention on Climate Change and advanced most recently through the Paris Climate Agreement. In parallel, sub-national actors have set greenhouse gas (GHG) reduction goals and developed corresponding climate mitigation plans. Within the U.S., multi-state coalitions have formed to facilitate coordination of related science and policy. Here, utilizing the forum of the NASA Carbon Monitoring System’s Multi-State Working Group, we collected and reviewed climate mitigation plans for 11 states in the Regional Greenhouse Gas Initiative region of the Eastern U.S. For each state we reviewed the (a) policy framework for climate mitigation, (b) GHG reduction goals, (c) inclusion of forest activities in the state’s climate action plan, (d) existing science used to quantify forest carbon estimates, and (e) stated needs for forest carbon monitoring science. Across the region, we found important differences across all categories. While all states have GHG reduction goals and framework documents, nearly three-quarters of all states do not account for forest carbon when planning GHG reductions; those that do account for forest carbon use a variety of scientific methods with various levels of planning detail and guidance. We suggest that a common, efficient, standardized forest carbon monitoring system would provide important benefits to states and the geographic region as a whole. In addition, such a system would allow for more effective transparency and progress tracking to support state, national, and international efforts to increase ambition and implementation of climate goals.

BACKGROUND:Tuberculosis is a major cause of morbidity and mortality in the developing world. Drug resistance, which is predicted to rise in many countries worldwide, threatens tuberculosis treatment and control. OBJECTIVE:To identify features associated with treatment failure and to predict which patients are at highest risk of treatment failure. METHODS:On a multi-country dataset managed by the National Institute of Allergy and Infectious Diseases we applied various machine learning techniques to identify factors statistically associated with treatment failure and to predict treatment failure based on baseline demographic and clinical characteristics alone. RESULTS:The complete-case analysis database consisted of 587 patients (68% males) with a median (p25-p75) age of 40 (30-51) years. Treatment failure occurred in approximately one fourth of the patients. The features most associated with treatment failure were patterns of drug sensitivity, imaging findings, findings in the microscopy Ziehl-Nielsen stain, education status, and employment status. The most predictive model was forward stepwise selection (AUC: 0.74), although most models performed at or above AUC 0.7. A sensitivity analysis using the 643 original patients filling the missing values with multiple imputation showed similar predictive features and generally increased predictive performance. CONCLUSION:Machine learning can help to identify patients at higher risk of treatment failure. Closer monitoring of these patients may decrease treatment failure rates and prevent emergence of antibiotic resistance. The use of inexpensive basic demographic and clinical features makes this approach attractive in low and middle-income countries.

Aristotle admits the possibility of many vices opposed to one virtue, but insists that there are always at least two, related as deficiency and excess. The doctrine that virtue is in a mean is thus both true and useful.

Kazmi’s systemic review concludes on the positive influence of the computer use on the biomedical aspect of the consultation interaction, and the adverse effect on the psychosocial dimension. It broaches concerns about the availability of high-quality studies focusing on the doctor–patient interactions. However, there are visible limitations associated with the search strategy employed, which indeed can be considered as a common challenge for reviews in this field of interaction research involving doctor, patient, and computer.

The issue of which measure of inflation ought to be targeted by policymakers has been extensively analysed, but the equally important issue of which inflation rate is actually targeted by policymakers in practice has been given much less attention. The paper addresses this question, using data for the UK, a country where differences among the alternative measures are especially marked. We estimate simple Taylor-like monetary policy rules, using several different measures of inflation. We find that plausible models can be obtained for each of the different measures, suggesting that it may not matter which is used in empirical analysis. Models using the RPI measure of inflation have a slight empirical advantage which reflects the ability better to explain monetary policy in more turbulent circumstances.

The wisdom of ‘smart’ development increasingly shapes urban sustainability in Europe and beyond. Yet, the ‘smart city’ paradigm has been critiqued for favouring technological solutions and business interests over social inclusion and urban innovation. Despite the rhetoric of ‘citizen-centred approaches’ and ‘user-generated data’, the level of stakeholder engagement and public empowerment is still in question. It is unclear how smart city initiatives are developing common visions according to the principles of sustainable urban development. This paper examines how data governance in particular is framed in the new smart city agenda that is focused on sustainability. The challenges and opportunities of data governance in sustainability-driven smart city initiatives are articulated within a conceptual Framework on Sustainable Smart City Data Governance. Drawing on three cases from European countries and a stakeholder survey, the paper shows how governance of data can underpin urban smart and sustainable development solutions. The paper presents insights and lessons from this multi-case study, and discusses risks, challenges, and future research.