Diagnostic accuracy of a brief screening tool forAttention Deficit/Hyperactivity Disorder in UK prison inmates

BackgroundAttention deficit hyperactivity disorder (ADHD) is overrepresented in prison, making it imperative to identify a screening tool that can be quickly applied to efficiently detect the disorder. We explored the discrimination ability of a widely used ADHD screen, the Barkley Adult ADHD Rating Scale (BAARS-IV), against a clinical diagnostic interview. A brief version of the screen was then developed in order to simplify its use in the prison context, and maximize its diagnostic properties.MethodA cross-sectional study of 390 male prison inmates was performed in the UK, all participants were screened and interviewed via the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2).ResultsA total of 47 (12.1%) inmates screened positive for ADHD using the full BAARS-IV, and 96 (24.6%) were clinically diagnosed, for a sensitivity of 37.9 and a specificity of 96.3. Our models identified the six items that most predicted ADHD diagnosis, with adjusted odds ratios ranging from 2.66 to 4.58. Sensitivity, specificity and accuracy were 0.82, 0.84 and 0.84, respectively, for the developed brief scale, and 0.71, 0.85 and 0.81 for its validation. Weighted probability scores produced an area under the curve of 0.89 for development, and 0.82 for validation of the brief scale.ConclusionsThe original BAARS-IV performed poorly at identifying prison inmates with ADHD. Our developed brief scale substantially improved diagnostic accuracy. The brief screening instrument has great potential to be used as an accurate and resource-effective tool to screen young people and adults for likely ADHD in the criminal justice system.</jats:sec

Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease

Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown. Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis. Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death. Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population

Real time dynamic strain monitoring of optical links using the backreflection of live PSK data.

A major cause of faults in optical communication links is related to unintentional third party intrusions (normally related to civil/agricultural works) causing fiber breaks or cable damage. These intrusions could be anticipated and avoided by monitoring the dynamic strain recorded along the cable. In this work, a novel technique is proposed to implement real-time distributed strain sensing in parallel with an operating optical communication channel. The technique relies on monitoring the Rayleigh backscattered light from optical communication data transmitted using standard modulation formats. The system is treated as a phase-sensitive OTDR (ΦOTDR) using random and non-periodical non-return-to-zero (NRZ) phase-shift keying (PSK) pulse coding. An I/Q detection unit allows for a full (amplitude, phase and polarization) characterization of the backscattered optical signal, thus achieving a fully linear system in terms of ΦOTDR trace coding/decoding. The technique can be used with different modulation formats, and operation using 4 Gbaud single-polarization dual PSK and 4 Gbaud dual-polarization quadrature PSK is demonstrated. As a proof of concept, distributed sensing of dynamic strain with a sampling of 125 kHz and a spatial resolution of 2.5 cm (set by the bit size) over 500 m is demonstrated for applied sinusoidal strain signals of 500 Hz. The limitations and possibilities for improvement of the technique are also discussed.This work was supported by the European Research Council through Starting Grant UFINE (Grant no. 307441), the Spanish MINECO through project TEC2013-45265-R, PCIN-2015- 219, and the regional program SINFOTON-CM: S2013/MIT-2790. HFM acknowledges EU funding through the FP7 ITN ICONE program, gr. #608099. SML acknowledges funding from the Spanish MINECO through a “Ramon y Cajal” contract. UK EPSRC funding through project EP/J008842/1

Characterization of growth and metabolism of the haloalkaliphile Natronomonas pharaonis

Natronomonas pharaonis is an archaeon adapted to two extreme conditions: high salt concentration and alkaline pH. It has become one of the model organisms for the study of extremophilic life. Here, we present a genome-scale, manually curated metabolic reconstruction for the microorganism. The reconstruction itself represents a knowledge base of the haloalkaliphile's metabolism and, as such, would greatly assist further investigations on archaeal pathways. In addition, we experimentally determined several parameters relevant to growth, including a characterization of the biomass composition and a quantification of carbon and oxygen consumption. Using the metabolic reconstruction and the experimental data, we formulated a constraints-based model which we used to analyze the behavior of the archaeon when grown on a single carbon source. Results of the analysis include the finding that Natronomonas pharaonis, when grown aerobically on acetate, uses a carbon to oxygen consumption ratio that is theoretically near-optimal with respect to growth and energy production. This supports the hypothesis that, under simple conditions, the microorganism optimizes its metabolism with respect to the two objectives. We also found that the archaeon has a very low carbon efficiency of only about 35%. This inefficiency is probably due to a very low P/O ratio as well as to the other difficulties posed by its extreme environment

N = 2 supersymmetric sigma-models and duality

For two families of four-dimensional off-shell N = 2 supersymmetric nonlinear sigma-models constructed originally in projective superspace, we develop their formulation in terms of N = 1 chiral superfields. Specifically, these theories are: (i) sigma-models on cotangent bundles T*M of arbitrary real analytic Kaehler manifolds M; (ii) general superconformal sigma-models described by weight-one polar supermultiplets. Using superspace techniques, we obtain a universal expression for the holomorphic symplectic two-form \omega^{(2,0)} which determines the second supersymmetry transformation and is associated with the two complex structures of the hyperkaehler space T*M that are complimentary to the one induced from M. This two-form is shown to coincide with the canonical holomorphic symplectic structure. In the case (ii), we demonstrate that \omega^{(2,0)} and the homothetic conformal Killing vector determine the explicit form of the superconformal transformations. At the heart of our construction is the duality (generalized Legendre transform) between off-shell N = 2 supersymmetric nonlinear sigma-models and their on-shell N = 1 chiral realizations. We finally present the most general N = 2 superconformal nonlinear sigma-model formulated in terms of N = 1 chiral superfields. The approach developed can naturally be generalized in order to describe 5D and 6D superconformal nonlinear sigma-models in 4D N = 1 superspace.Comment: 31 pages, no figures; V2: reference and comments added, typos corrected; V3: more typos corrected, published versio

Extended supersymmetric sigma models in AdS_4 from projective superspace

There exist two superspace approaches to describe N=2 supersymmetric nonlinear sigma models in four-dimensional anti-de Sitter (AdS_4) space: (i) in terms of N=1 AdS chiral superfields, as developed in arXiv:1105.3111 and arXiv:1108.5290; and (ii) in terms of N=2 polar supermultiplets using the AdS projective-superspace techniques developed in arXiv:0807.3368. The virtue of the approach (i) is that it makes manifest the geometric properties of the N=2 supersymmetric sigma-models in AdS_4. The target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures. The power of the approach (ii) is that it allows us, in principle, to generate hyperkahler metrics as well as to address the problem of deformations of such metrics. Here we show how to relate the formulation (ii) to (i) by integrating out an infinite number of N=1 AdS auxiliary superfields and performing a superfield duality transformation. We also develop a novel description of the most general N=2 supersymmetric nonlinear sigma-model in AdS_4 in terms of chiral superfields on three-dimensional N=2 flat superspace without central charge. This superspace naturally originates from a conformally flat realization for the four-dimensional N=2 AdS superspace that makes use of Poincare coordinates for AdS_4. This novel formulation allows us to uncover several interesting geometric results.Comment: 88 pages; v3: typos corrected, version published in JHE

An automated approach to identify scientific publications reporting pharmacokinetic parameters [version 1; peer review: awaiting peer review]

Pharmacokinetic (PK) predictions of new chemical entities are aided by prior knowledge from other compounds. The development of robust algorithms that improve preclinical and clinical phases of drug development remains constrained by the need to search, curate and standardise PK information across the constantly-growing scientific literature. The lack of centralised, up-to-date and comprehensive repositories of PK data represents a significant limitation in the drug development pipeline.In this work, we propose a machine learning approach to automatically identify and characterise scientific publications reporting PK parameters from in vivo data, providing a centralised repository of PK literature. A dataset of 4,792 PubMed publications was labelled by field experts depending on whether in vivo PK parameters were estimated in the study. Different classification pipelines were compared using a bootstrap approach and the best-performing architecture was used to develop a comprehensive and automatically-updated repository of PK publications. The best-performing architecture encoded documents using unigram features and mean pooling of BioBERT embeddings obtaining an F1 score of 83.8% on the test set. The pipeline retrieved over 121K PubMed publications in which in vivo PK parameters were estimated and it was scheduled to perform weekly updates on newly published articles. All the relevant documents were released through a publicly available web interface (https://app.pkpdai.com) and characterised by the drugs, species and conditions mentioned in the abstract, to facilitate the subsequent search of relevant PK data. This automated, open-access repository can be used to accelerate the search and comparison of PK results, curate ADME datasets, and facilitate subsequent text mining tasks in the PK domain.</ns4:p

Heart or heart-lung transplantation for patients with congenital heart disease in England

BACKGROUND: Increased longevity in patients with congenital heart disease (CHD) is associated with late complications, mainly heart failure, which may not be amenable to redo surgery and become refractory to medical therapy and so, trigger referral for transplantation. We assessed the current role and future prospects of heart and heart-lung transplantation for patients with CHD in England. METHODS: We performed a retrospective analysis of hospital episodes for England for 1997-2015, identifying patients with a CHD code (ICD-10 'Q2xx.x'), who underwent heart or heart-lung transplantation. RESULTS: In total, 469 transplants (82.2% heart and 17.8% heart-lung) were performed in 444 patients. Half of patients transplanted had mild or moderate CHD complexity, this percentage increased with time (p=0.001). While overall, more transplantations were performed over the years, the proportion of heart-lung transplants declined (p<0.0001), whereas the proportion of transplants performed in adults remained static. Mortality was high during the first year, especially after heart-lung transplantation, but remained relatively low thereafter. Older age and heart-lung transplantation were strong predictors of death. While an increase in CHD transplants is anticipated, actual numbers in England seem to lag behind the increase in CHD patients with advanced heart failure. CONCLUSIONS: The current and future predicted increase in the numbers of CHD transplants does not appear to parallel the expansion of the CHD population, especially in adults. Further investment and changes in policy should be made to enhance the number of donors and increase CHD transplant capacity to address the increasing numbers of potential CHD recipients and optimise transplantation outcomes in this growing population

ReadClear: An Assistive Reading Tool for People Living with Posterior Cortical Atrophy

BACKGROUND: Progressive reading impairment is an early and debilitating symptom of posterior cortical atrophy (PCA) arising from the progressive deterioration of visual processing skills. OBJECTIVE: The goal of this study was to test the effectiveness of a purpose-built reading app (ReadClear) co-produced with people living with PCA and designed to reduce the reading difficulties experienced by this population (e.g., getting lost in the page and missing words when reading). METHODS: Twenty subjects with PCA were included in a cross-over design home-based study aimed at determining whether ReadClear could 1) enhance the subjective reading experience (reading pleasantness) and 2) improve reading accuracy (reducing the number of reading errors) compared with a sham condition (a standard e-reader). RESULTS: Reading using ReadClear provided a better subjective reading experience than sham (p = 0.018, d = 0.5) and significantly reduced the percentage of reading errors (p <  0.0001, r = 0.82), particularly errors due to omissions (p = 0.01, r = 0.50), repeated words (p = 0.002, r = 0.69), and regressions in the text (p = 0.003, r = 0.69). We found that different kinds of reading errors were related to specific neuropsychological profiles. CONCLUSION: ReadClear can assist reading in people living with PCA by reducing the number of reading errors and improving the subjective reading experience of users