Multi-qubit entanglement and algorithms on a neutral-atom quantum computer.

Gate-model quantum computers promise to solve currently intractable computational problems if they can be operated at scale with long coherence times and high-fidelity logic. Neutral-atom hyperfine qubits provide inherent scalability owing to their identical characteristics, long coherence times and ability to be trapped in dense, multidimensional arrays1. Combined with the strong entangling interactions provided by Rydberg states2-4, all the necessary characteristics for quantum computation are available. Here we demonstrate several quantum algorithms on a programmable gate-model neutral-atom quantum computer in an architecture based on individual addressing of single atoms with tightly focused optical beams scanned across a two-dimensional array of qubits. Preparation of entangled Greenberger-Horne-Zeilinger (GHZ) states5 with up to six qubits, quantum phase estimation for a chemistry problem6 and the quantum approximate optimization algorithm (QAOA)7 for the maximum cut (MaxCut) graph problem are demonstrated. These results highlight the emergent capability of neutral-atom qubit arrays for universal, programmable quantum computation, as well as preparation of non-classical states of use for quantum-enhanced sensing.

Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Thirty-day mortality following surgical management of hip fractures during the COVID-19 pandemic: findings from a prospective multi-centre UK study.

PURPOSE: Thirty-day mortality of patients with hip fracture is well researched and predictive; validated scoring tools have been developed (Nottingham Hip Fracture Score, NHFS). COVID-19 has significantly greater mortality in the elderly and comorbid patients which includes hip fracture patients. Non-operative treatment is not appropriate due to significantly higher mortality, and therefore, these patients are often exposed to COVID-19 in the peri-operative period. What is unclear is the effect of concomitant COVID-19 infection in these patients. METHODS: A multicentre prospective study across ten sites in the United Kingdom (responsible for 7% of hip fracture patients per annum in the UK). Demographic and background information were collected by independent chart review. Data on surgical factors included American Society of Anesthesiologists (ASA) score, time to theatre, Nottingham Hip fracture score (NHFS) and classification of fracture were also collected between 1st March 2020 and 30th April 2020 with a matched cohort from the same period in 2019. RESULTS: Actual and expected 30-day mortality was found to be significantly higher than expected for 2020 COVID-19 positive patients (RR 3.00 95% CI 1.57-5.75, p < 0.001), with 30 observed deaths compared against the 10 expected from NHFS risk stratification. CONCLUSION: COVID-19 infection appears to be an independent risk factor for increased mortality in hip fracture patients. Whilst non-operative management of these fractures is not suggested due to the documented increased risks and mortality, this study provides evidence to the emerging literature of the severity of COVID-19 infection in surgical patients and the potential impact of COVID-19 on elective surgical patients in the peri-operative period.

Addressing Syndemics and Self-care in Individuals with Uncontrolled HIV: An Open Trial of a Transdiagnostic Treatment.

Interventions addressing syndemics and ART adherence are needed for individuals with uncontrolled HIV and psychosocial problems. Twenty-seven participants with detectable HIV plasma viral load (PVL) or recent STI participated in an open trial of transdiagnostic adherence counseling and cognitive behavioral therapy. Outcomes were collected at baseline, 4-, and 8-months. Log PVL improved from baseline to 4-month (γ = - 1.13, 95% CI - 1.72, - 0.55, p < 0.001) and 8-month (γ = - 0.93, 95% CI - 1.57, - 0.30, p = 0.006), with more participants suppressed at 4- (χ2(1) = 9.09, p = 0.001) and 8-month (χ2(1) = 5.14, p = 0.016). Self-reported adherence improved across major assessments (γ = 0.87, 95% CI 0.28, 1.46, p = .005); Wisepill adherence did not. Negative affect declined during treatment (γ = - 0.28, 95% CI - 0.40, - 0.16, p < 0.001), with improvement at 4- (γ = - 4.34, 95% CI - 6.99, - 1.69, p = 0.002) but not 8-month. Positive affect trended positively during treatment and from baseline to 4-month, with significant 8-month improvement (γ = 3.84, 95% CI 0.33, 7.44, p = 0.04). Depressive symptoms did not change. In a complicated sample of participants selected for uncontrolled HIV, the intervention yielded improved PVL and self-reported adherence. Efforts to end HIV should improve upon strategies such as these, addressing syndemics. Registration: clinicaltrial.gov: NCT02696681.

An interdisciplinary and catchment approach to enhancing urban flood resilience: a Melbourne case.

This paper presents a novel interdisciplinary and catchment-based approach for exploring urban flood resilience. Our research identified and developed a diverse set of adaptation measures for Elwood, a suburb in Melbourne, Australia, that is vulnerable to pluvial and coastal flooding. We drew on methods from social science, urban design and environmental engineering to gain integrated insights into the opportunities for Elwood to increase its flood resilience and urban liveability. Results showed that an appropriate balance of social, infrastructural and urban design responses would be required to retreat from, accommodate and protect against flood risk. These would also deliver broader benefits such as securing water supplies through harvested stormwater and mitigating extreme heat through greener landscapes. Our interdisciplinary approach demonstrated the value of (i) engaging with the community to understand their concerns, aspirations and adaptation ideas, (ii) exploring design measures that densify and use urban forms in ways that implement adaptation measures while responding to local context, (iii) adopting modelling techniques to test the performance, robustness and economic viability of possible adaptation solutions, and (iv) innovating governance arrangements and principles needed to improve flood resilience in the Elster Creek catchment. Our research also provided valuable insight on how to operationalize interdisciplinary work in practice, highlighting the importance of sharing an impact agenda, taking a place-based approach, developing a common conceptual framework, and fostering a constructive team culture. This article is part of the theme issue 'Urban flood resilience'.

Connecting the dots: a comparison of network analysis and exploratory factor analysis to examine psychosocial syndemic indicators among HIV-negative sexual minority men.

Syndemics, or comorbid and mutually reinforcing psychosocial problems, are associated with increased HIV risk among men who have sex with men (MSM). Although the dynamic interplay among syndemic indicators is theorized to be crucial for increasing risk of HIV acquisition, novel approaches are needed to understand how these syndemic problems interrelate. This study examined the associations between nine self-reported syndemic indicators in 194 MSM at high risk of HIV acquisition. We compared exploratory factor analyses (EFA) to a network analysis. In the present study, network analysis consisted of edges representing bidirectional partial polychoric correlations between nodes, which represent psychosocial syndemic indicators. EFA yielded a 1-factor solution including suicidal ideation (SI), injection drug use (IDU), depression, social anxiety, intimate partner violence, substance use, and sexual compulsivity, and excluded heavy drinking and childhood sexual abuse. Network analysis yielded a pattern of interconnectedness with the most central nodes being SI, IDU, substance use, and depression. Statistically significant relationships (absolute edge weights) were found between SI and depression, social anxiety, and IDU, and IDU and substance use. These results suggest that depression and substance use, especially more severe presentations of these conditions such as SI and IDU, are prominent interconnected components of the HIV syndemic among MSM at high risk for HIV acquisition. SI, IDU, substance use, and depression may indeed be prudent targets of intervention. Future research on the inclusion of these syndemic indicators in analytical models involving interaction terms may be warranted.

Correction to: Thirty-day mortality following surgical management of hip fractures during the COVID-19 pandemic: findings from a prospective multi-centre UK study.

The published online version contains mistake, as the Fig. 1 legend should read "Kaplan-Meier survival curve for 30-day survival for 2020 cohort COVID-19 positive vs COVID-19 negative" whilst the Fig. 2 legend should read "Kaplan-Meier survival curve for 30-day survival 2020 COVID-19 negative group vs 2019 cohort".

The incidence of anterior pituitary hormone deficiencies in patients with microprolactinoma and idiopathic hyperprolactinaemia.

INTRODUCTION: Patients with microprolactinoma and idiopathic hyperprolactinaemia are not generally considered to be at risk of hypopituitarism and are therefore not routinely screened for this abnormality. In our clinical practice, we have observed a number of patients with nonmacroadenomatous hyperprolactinaemia to have anterior pituitary hormone deficits. AIMS: We aimed to establish the frequency and clinical significance of anterior pituitary hormone deficiencies, comparing patients with radiologically proven microprolactinomas and patients with idiopathic hyperprolactinaemia. STUDY DESIGN: We retrospectively examined the casenotes of 206 patients with hyperprolactinaemia from our centre. Patients who did not fit the profile of surgically naïve microprolactinoma or idiopathic hyperprolactinaemia or who had incomplete data were excluded, resulting in a study group of 56 patients. RESULTS: A total of 35 patients with MRI evidence of microprolactinoma were identified, three (8.57%) of whom had one or more anterior pituitary hormone deficiencies. A total of 21 patients with MRI-negative idiopathic hyperprolactinaemia were identified, nine (42%) of whom had one or more anterior pituitary hormone deficiencies (P<.01). Only one patient in the MRI-positive group had deficiency that required hormone replacement, in contrast six patients in the MRI-negative group had deficiencies that were of clinical significance and which required hormone replacement. SUMMARY: This study shows a clinically significant incidence of anterior pituitary hormone deficiency in patients with idiopathic hyperprolactinaemia. The authors recommend that dynamic pituitary assessment should be considered routinely in this patient group. A prospective study would be required to assess the underlying cause for these abnormalities, as they suggest a nontumour pan-pituitary process.

A comparative analysis of the patient characteristics and cost of managing intravenous drug users (IVDU) with soft tissue abscesses with non-IVDU.

BACKGROUND: Intravenous drug users (IVDU) often present to hospitals with complex co-morbidities, associated with prolonged in-patient admissions. The aim of this study was to compare a cohort of IVDU patients with soft tissue abscesses with non-IVDUs. We analysed the demographics, comorbidities, location of abscesses, multidisciplinary input and financial costs of managing both groups. METHODS: A retrospective cohort study was conducted between January 2010 and September 2013. Two age and sex matched cohorts were compared: IVDU and non-IVDU. RESULTS: We identified 44 IVDU patients and 54 non-IVDU patients. The IVDU had higher rates of smoking (89% p < 0.001) and unemployment (73% p < 0.05). The most common comorbidities in the IVDU cohort were hepatitis C (17%) and HIV (14%), whereas diabetes mellitus (15%) and hypertension (11%) were the most common in the non-IVDUs (p < 0.01). The most common location for an abscess in non-IVDU patients was the hand, whereas IVDU patients had abscesses in their groin. Groin injecting led to a referral to multiple specialties. The median length of stay for the IVDU patients was 4 days and for non-IVDU patients 1 day (p < 0.01). The average cost of managing IVDU patients in our unit was £1280: for non- IVDU the cost was £530 (p < 0.001). CONCLUSIONS: IVDU patients with soft tissue abscesses have higher rates of smoking, unemployment, infection with hepatitis C and HIV compared to a control group. We have suggested several recommendations to optimise the management of these patients including the implementation of an additional code to compensate for the complexity of their management.

Vancomycin therapeutics and monitoring: a contemporary approach.

Vancomycin remains a clinically useful antibiotic despite the advent of several alternative drugs. Optimising vancomycin therapy with therapeutic drug monitoring is widely recommended. The aim of therapeutic drug monitoring is to help the clinician to achieve target pharmacodynamic parameters in the case of vancomycin, an area under the concentration time curve/minimum inhibitory concentration ratio of ≥400. Vancomycin monitoring methods can be categorised into four categories: empiric trough concentrations; linear regression analysis (one-compartment model), population methods and Bayesian estimation procedures. Although the empiric trough concentrations and population methods are easy to use and require minimal resources, there are large differences in the published vancomycin model parameters. This demonstrates that there is great variance in pharmacokinetic parameters between the models and a single vancomycin model cannot be applied to all patient populations. The linear regression and Bayesian methods recommended more accurate dosage regimens; however, they require additional resources such as information technology and healthcare personnel with background training in pharmacokinetics. The Bayesian methods offered additional advantages such as calculation of doses based on a single-serum concentration and optimisation of the patient's previous pharmacokinetic data to determine subsequent dosage regimens. Computerised programs, utilising the Bayesian estimation procedures, are able to achieve target concentrations in a greater percentage of patients earlier in the course of therapy than the empiric trough concentrations and population methods. We recommend the use of these programs providing there is appropriate expertise available to make appropriate recommendations.

Women in trauma and orthopaedics: are we losing them at the first hurdle?

INTRODUCTION: Diversity in the healthcare workforce is associated with improved performance and patient-reported outcomes. Gender disparity in Trauma and Orthopaedics (T&O) is well recognised. The aim of this study was to compare factors that influence career choice in T&O between male and female final-year students. Furthermore, the trend of representation of women in T&O over the last decade was also compared with other surgical specialities. METHODS: An online survey of final-year students who attended nationally advertised T&O courses over a 2-year period was conducted. Data from NHS digital was obtained to assess gender diversity in T&O compared with other surgical specialities. RESULTS: A total of 414 students from 13 UK medical schools completed the questionnaire. Compared with male students (34.2%), a significantly higher proportion of women (65.8%) decided against a career in T&O, p<0.001. Factors that dissuaded a significantly higher percentage of women included gender bias, technical aspects of surgery, unsociable hours, on-call commitments, inadequate undergraduate training and interest in another specialty (p<0.05). Motivating factors for choosing a career in T&O were similar between both sexes. T&O was the surgical specialty with the lowest proportion of women at both consultant and trainee level over the last decade. CONCLUSION: T&O remains an unpopular career choice among women. To enhance recruitment of women in T&O, future strategies should be directed toward medical students. Universities, orthopaedic departments and societies must work collaboratively to embed culture change, improve the delivery of the undergraduate curriculum, and facilitate students' exposure to operating theatres and female role models.

Use of Ceftriaxone and Benzylpenicillin in Outpatient Parenteral Antimicrobial Therapy: Spectrum vs Cost.

Background: The application of antimicrobial stewardship (AMS) principles may entail increased cost to allow for narrower-spectrum therapy. Prescribing benzylpenicillin (BP) and ceftriaxone (CRO) for outpatient parenteral antimicrobial therapy (OPAT) demonstrates the complex challenge of this principle. The aim of this study is to analyze the use of BP and CRO in our OPAT program, including indications and relative cost. Methods: We analyzed all adult patients in our OPAT program who received intravenous BP or CRO over 1 year. We identified a "crossover group" of patients who could have received either agent. Economic comparison was based on acquisition cost of the therapy (drug, infuser, and preparation costs). Results: Of 105 eligible patients, 54 (51%) and 51 (49%) received BP and CRO, respectively. Forty (38%) patients were suitable for either agent; of these, the majority (n = 31, 78%) were treated with BP. Economic analysis demonstrated that the average daily cost of BP therapy was $93.76/d (AUD) vs $1.23/d for CRO. Thus, across our OPAT programs, we had an additional average cost of $92.53/patient/d to use BP instead of CRO. Program-wide the annual additional cost of using BP and thus applying this AMS strategy was $68 386.12. Conclusions: BP is often selected over CRO by clinicians, where possible, as recommended by the Australian guidelines; however, BP is associated with higher daily acquisition costs. More broadly, a number of narrower-spectrum agents may involve significantly higher costs than comparators; as such, the $92.53/d to prevent CRO exposure can be considered when applying other antimicrobial-substitution AMS interventions in an acute health care setting.

Prolonged carriage of resistant E. coli by returned travellers: clonality, risk factors and bacterial characteristics.

The aim of this study was to delineate the potential risks and dynamics of the prolonged carriage of resistant E. coli in returned travellers. A sample of 274 previously collected E. coli resistant to ceftriaxone (CRO), ciprofloxacin, gentamicin and/or nalidixic acid recovered from 102 travellers was studied. Travellers were assessed pre-travel then longitudinally (maximum 6 months) with peri-rectal/rectal swabs. Clonality was determined by REP-PCR and the presence of O25b-ST131 was assessed. Comparison was made longitudinally for individuals and between identified co-travellers. The risk of prolonged carriage was lower for CRO than for ciprofloxacin or gentamicin resistance. Repeated isolation of the same phenotype at different time points occurred in 19% of initial CRO-resistant carriers compared with 50% of ciprofloxacin- or gentamicin-resistant carriers. The duration of carriage was also longer for the latter resistance phenotypes (75th quartile 8 vs 62 and 63 days respectively). In multivariate analysis, risks of prolonged carriage included antimicrobial use whilst travelling (3.3, 1.3-8.4) and phylogenetic group B2 (9.3, 3.4-25.6) and D (3.8, 1.6-8.8). Clonality amongst longitudinal isolates from the same participant was demonstrated in 92% of participants who were assessable and most marked amongst CRO-resistant isolates. ST-131 was surprisingly infrequent (3% of participants). Prolonged carriage of ciprofloxacin- and gentamicin-resistant isolates is more frequent and prolonged than CRO resistance after travel. Risks of prolonged carriage indicate a contribution of host and bacterial factors to this carriage. These require further elucidation. The strong clonality identified suggests that carriage of a "phenotype" was mediated by persistence of bacteria/plasmid combinations rather than persistence of the plasmid after horizontal transfer to other bacteria.

Release of individual surgeon data to the public: patients' and surgeons' views.

BACKGROUND: Limited surgeon-specific outcomes data are currently released to the public. Existing schemes generally result from the recommendations of public enquiries, addressing breaches to patient safety and malpractice. We found limited evidence in the literature about patients' or orthopaedic surgeons' wishes regarding the release of such data to the public. METHODS: We surveyed 80 joint replacement patients and 41 orthopaedic surgeons regarding their wishes concerning collection and release of individual surgeon data to the public. RESULTS: Of 80 patients, 30% (24/80) were aware of data on the NHS-My Choices website, 16% (13/80) had reviewed data prior to operation and 95% (76/80) wanted data concerning surgeons' experience, length of stay and complications including revisions. Patients expected more current monitoring of data than occurs. Of 41 surgeons, 20% (8/41) thought national joint registry (NJR) derived data accurately reflected their NHS work. Surgeons did not think this data improved patient outcomes (34%, 14/41), and that it reduced innovation (61%, 25/41) and training (75%, 31/41) and increased risk of adverse behaviour (61%, 25/41). Surgeons wanted a minimal data set accurately presented and risk adjusted. CONCLUSION: In the future, it is likely that more individual surgeon data will be released to the public. There needs to be an agreed, accurate minimum dataset collected, reviewed in local clinical governance meetings and published with explanatory notes regarding the interfering variables and what conclusions can be drawn regarding the ability of the surgeon. This process needs to be overseen by an independent body trusted by the public.

Release of individual surgeon data to the public: patients' and surgeons' views.

BACKGROUND: Limited surgeon-specific outcomes data are currently released to the public. Existing schemes generally result from the recommendations of public enquiries, addressing breaches to patient safety and malpractice. We found limited evidence in the literature about patients' or orthopaedic surgeons' wishes regarding the release of such data to the public. METHODS: We surveyed 80 joint replacement patients and 41 orthopaedic surgeons regarding their wishes concerning collection and release of individual surgeon data to the public. RESULTS: Of 80 patients, 30% (24/80) were aware of data on the NHS-My Choices website, 16% (13/80) had reviewed data prior to operation and 95% (76/80) wanted data concerning surgeons' experience, length of stay and complications including revisions. Patients expected more current monitoring of data than occurs. Of 41 surgeons, 20% (8/41) thought national joint registry (NJR) derived data accurately reflected their NHS work. Surgeons did not think this data improved patient outcomes (34%, 14/41), and that it reduced innovation (61%, 25/41) and training (75%, 31/41) and increased risk of adverse behaviour (61%, 25/41). Surgeons wanted a minimal data set accurately presented and risk adjusted. CONCLUSION: In the future, it is likely that more individual surgeon data will be released to the public. There needs to be an agreed, accurate minimum dataset collected, reviewed in local clinical governance meetings and published with explanatory notes regarding the interfering variables and what conclusions can be drawn regarding the ability of the surgeon. This process needs to be overseen by an independent body trusted by the public.

The impact of mentoring in trauma and orthopaedic training: a systematic review.

INTRODUCTION: Trauma and orthopaedics is renowned for being a challenging yet rewarding career. The value of mentorship in medical and surgical training is known to be beneficial; however, the prevalence and quality of mentorship opportunities in orthopaedics are less well studied. Identifying the strengths and weaknesses of mentoring programmes in orthopaedic training and recognising barriers to effective mentorship are key to unlocking the full potential of future orthopaedic surgeons. METHODS: A comprehensive search of PubMed, Medline, EMBASE and the Cochrane Library was performed. All studies published in the English language that reported data on mentorship programmes in orthopaedic training were included. FINDINGS: A total of 23 studies met the inclusion criteria. These studies demonstrated that formal mentorship programmes in orthopaedics are lacking but are sought after, with a positive influence on satisfaction and future career choice/subspecialty selection identified. Several barriers to mentoring in the field were recognised including the difficulty faced by female trainees, the availability of mentors and time constraints. The opportunity to choose a mentor, a mentor with the same interests, regular meetings and the option of gender congruent mentorship were all identified as crucial requirements for effective mentorship. CONCLUSION: Mentorship opportunities must be more accessible to all orthopaedic trainees alike and should aim to incorporate the attributes identified to provide the highest calibre of training to prospective orthopaedic surgeons.

Fractional anisotropy of cerebral white matter and thickness of cortical gray matter across the lifespan.

We examined age trajectories of fractional anisotropy (FA) of cerebral white matter (WM) and thickness of cortical gray matter (GM) in 1031 healthy human subjects (aged 11-90 years). Whole-brain FA and GM thickness values followed quadratic trajectories with age but the relationship between them was linear, indicating that a putative biological mechanism may explain the non-linearity of their age trajectories. Inclusion of the FA values into the quadratic model of the whole-brain and regional GM thickness changes with age made the effect of the age(2) term no longer significant for the whole-brain GM thickness and greatly reduced its significance for regional GM thickness measurements. The phylogenetic order of cerebral myelination helped to further explain the intersubject variability in GM thickness. FA values for the early maturing WM were significantly better (p=10(-6)) at explaining variability in GM thickness in maturing (aged 11-20) subjects than FA values for the late maturing WM. The opposite trend was observed for aging subjects (aged 40-90) where FA values for the late maturing WM were better (p=10(-16)) at explaining the variability in GM thickness. We concluded that the non-linearity of the age trajectory for GM thickness, measured from T1-weighted MRI, was partially explained by the heterogeneity and the heterochronicity of the age-related changes in the microintegrity of cerebral WM. We consider these findings as the evidence that the measurements of age-related changes in GM thickness and FA are driven, in part, by a common biological mechanism, presumed to be related to changes in cerebral myelination.

Somnolence in adult craniopharyngioma patients is a common, heterogeneous condition that is potentially treatable.

CONTEXT AND OBJECTIVE: Somnolence and obesity are prevalent in craniopharyngioma patients. We hypothesized that somnolence was because of obstructive sleep apnoea in craniopharyngioma patients. DESIGN, PATIENTS AND MEASUREMENTS: We assessed prevalence of somnolence and sleep apnoea in 28 craniopharyngioma and 23 obese controls attending a tertiary referral centre, by means of the Epworth Sleepiness Score (ESS) and polysomnography. All subjects with sleep apnoea were offered continuous positive airway pressure therapy (CPAP) or modafinil. All craniopharyngioma patients, with unexplained somnolence, were offered modafinil. RESULTS: Somnolence was reported by 20/28 (71·5%) craniopharyngioma patients and 4/23 (17%) obese subjects (P < 0·001). Median ESS was 7·5 (IQR 6, 10·7) in craniopharyngioma patients and 4·0 (4,8) in controls, P < 0·01. Eleven somnolent craniopharyngioma patients had obstructive sleep apnoea, in whom treatment led to a reduction in ESS by 6·4 ± 1·4, P = 0·01. Among the remaining nine patients, five were offered modafinil therapy, of whom four had benefit, three were not compliant with hormone replacement, and one died before intervention. There was no difference in the prevalence of obstructive sleep apnoea between craniopharyngioma (n = 13, 46%) and obese subjects (n = 14, 61%, P = 0·4). Body mass index (BMI) does not correlate with apnoea hypopnoea index [apnoea - hypopnoea index (AHI), r = 0·25, P = 0·08], which suggests that obesity alone does not explain the prevalence of sleep apnoea in craniopharyngioma patients. CONCLUSIONS: Somnolence is common in craniopharyngioma patients and in the majority is because of obstructive sleep apnoea. An additional group of somnolent craniopharyngioma patients benefits from modafinil.

Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity.

The new Australian Therapeutic Guidelines: Antibiotic, version 14 have revised the recommendations for the use and monitoring of aminoglycosides. The guidelines have clear distinctions between empirical and directed therapy as well as revised recommendations about the monitoring of aminoglycosides. This has led many clinicians to review their current practice with regard to the use of aminoglycosides. This review summarizes why aminoglycosides are still a valid treatment option and discusses the rationale for current dosing regimens in Gram-negative infections. In particular it focuses on the various methods for monitoring aminoglycosides that are currently being used. The aminoglycoside monitoring methods can be categorized into three groups: linear regression analysis (one compartment model), population methods and Bayesian estimation procedures. Although the population methods are easy to use and require minimal resources they can recommend clinically inappropriate doses as they have constant pharmacokinetic parameters and are not valid in special population groups, that is, renal impairment. The linear regression and Bayesian methods recommend more accurate dosage regimens; however, they require additional resources, such as information technology and healthcare personnel with background training in pharmacokinetics. The Bayesian methods offer additional advantages, such as calculation of doses based on a single serum concentration and optimization of the patient's previous pharmacokinetic data, in order to determine subsequent dosage regimens. We recommend the Bayesian estimation procedures be used, wherever feasible. However, they require the expertise of healthcare practitioners with a good understanding of pharmacokinetic principles, such as clinical pharmacists/clinical pharmacologists, in order to make appropriate recommendations.

Uncovering turbulent plasma dynamics via deep learning from partial observations.

One of the most intensely studied aspects of magnetic confinement fusion is edge plasma turbulence which is critical to reactor performance and operation. Drift-reduced Braginskii two-fluid theory has for decades been widely applied to model boundary plasmas with varying success. Towards better understanding edge turbulence in both theory and experiment, we demonstrate that a physics-informed deep learning framework constrained by partial differential equations can accurately learn turbulent fields consistent with the two-fluid theory from partial observations of electron pressure which is not otherwise possible using conventional equilibrium models. This technique presents a paradigm for the advanced design of plasma diagnostics and validation of magnetized plasma turbulence theories in challenging thermonuclear environments.