Towards a micropositioning system for targeted drug delivery in wireless capsule endoscopy

This paper describes a novel micropositioning mechanism for achieving 1ml of targeted drug delivery within wireless capsule endoscopes. The mechanism allows a needle to be positioned within a 22.5° segment of a cylindrical capsule and be extendible by up to 4mm. The mechanism achieves both these functions using only a single micromotor and occupying a volume of just 200mm³ (including micromotor), this represents only 6.6% of the total available space. Through a detailed stress analysis it has been shown that the proposed mechanism can be fabricated using FDA approved materials and requires a power budget of under 3.3% of the available capacity. It is envisaged this mechanism would empower a new breed of capsule microrobots for therapy in addition to diagnostics for pathologies such as ulcerative colitis and small intestinal Crohn’s disease.Accepted versio

Can we screen for pancreatic cancer? Identifying a sub-population of patients at high risk of subsequent diagnosis using machine learning techniques applied to primary care data.

BACKGROUND: Pancreatic cancer (PC) represents a substantial public health burden. Pancreatic cancer patients have very low survival due to the difficulty of identifying cancers early when the tumour is localised to the site of origin and treatable. Recent progress has been made in identifying biomarkers for PC in the blood and urine, but these cannot be used for population-based screening as this would be prohibitively expensive and potentially harmful. METHODS: We conducted a case-control study using prospectively-collected electronic health records from primary care individually-linked to cancer registrations. Our cases were comprised of 1,139 patients, aged 15-99 years, diagnosed with pancreatic cancer between January 1, 2005 and June 30, 2009. Each case was age-, sex- and diagnosis time-matched to four non-pancreatic (cancer patient) controls. Disease and prescription codes for the 24 months prior to diagnosis were used to identify 57 individual symptoms. Using a machine learning approach, we trained a logistic regression model on 75% of the data to predict patients who later developed PC and tested the model's performance on the remaining 25%. RESULTS: We were able to identify 41.3% of patients 60 years were similarly identified at 17 months, with 65% sensitivity, 57% specificity and, 61% AUC. We estimate that combining our algorithm with currently available biomarker tests could result in 30 older and 400 younger patients per cancer being identified as 'potential patients', and the earlier diagnosis of around 60% of tumours. CONCLUSION: After further work this approach could be applied in the primary care setting and has the potential to be used alongside a non-invasive biomarker test to increase earlier diagnosis. This would result in a greater number of patients surviving this devastating disease

Cognitive Neuropsychology of HIV-Associated Neurocognitive Disorders

Advances in the treatment of the human immunodeficiency virus (HIV) have dramatically improved survival rates over the past 10 years, but HIV-associated neurocognitive disorders (HAND) remain highly prevalent and continue to represent a significant public health problem. This review provides an update on the nature, extent, and diagnosis of HAND. Particular emphasis is placed on critically evaluating research within the realm of cognitive neuropsychology that aims to elucidate the component processes of HAND across the domains of executive functions, motor skills, speeded information processing, episodic memory, attention/working memory, language, and visuoperception. In addition to clarifying the cognitive mechanisms of HAND (e.g., impaired cognitive control), the cognitive neuropsychology approach may enhance the ecological validity of neuroAIDS research and inform the development of much needed novel, targeted cognitive and behavioral therapies

Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

© The Author(s). 2018Background: As part of a national programme to tackle ethnic inequalities, we conducted a systematic review and meta-analysis of research on ethnic inequalities in pathways to care for adults with psychosis living in England and/or Wales. Methods: Nine databases were searched from inception to 03.07.17 for previous systematic reviews, including forward and backward citation tracking and a PROSPERO search to identify ongoing reviews. We then carried forward relevant primary studies from included reviews (with the latest meta-analyses reporting on research up to 2012), supplemented by a search on 18.10.17 in MEDLINE, Embase, PsycINFO and CINAHL for primary studies between 2012 and 2017 that had not been covered by previous meta-analyses. Results: Forty studies, all conducted in England, were included for our updated meta-analyses on pathways to care. Relative to the White reference group, elevated rates of civil detentions were found for Black Caribbean (OR = 3.43, 95% CI = 2.68 to 4.40, n = 18), Black African (OR = 3.11, 95% CI = 2.40 to 4.02, n = 6), and South Asian patients (OR = 1.50, 95% CI 1.07 to 2.12, n = 10). Analyses of each Mental Health Act section revealed significantly higher rates for Black people under (civil) Section 2 (OR = 1.53, 95% CI = 1.11 to 2.11, n = 3). Rates in repeat admissions were significantly higher than in first admission for South Asian patients (between-group difference p < 0.01). Some ethnic groups had more police contact (Black African OR = 3.60, 95% CI = 2.15 to 6.05, n = 2; Black Caribbean OR = 2.64, 95% CI = 1.88 to 3.72, n = 8) and criminal justice system involvement (Black Caribbean OR = 2.76, 95% CI = 2.02 to 3.78, n = 5; Black African OR = 1.92, 95% CI = 1.32 to 2.78, n = 3). The White Other patients also showed greater police and criminal justice system involvement than White British patients (OR = 1.49, 95% CI = 1.03 to 2.15, n = 4). General practitioner involvement was less likely for Black than the White reference group. No significant variations over time were found across all the main outcomes. Conclusions: Our updated meta-analyses reveal persisting but not significantly worsening patterns of ethnic inequalities in pathways to psychiatric care, particularly affecting Black groups. This provides a comprehensive evidence base from which to inform policy and practice amidst a prospective Mental Health Act reform. Trial registration: CRD42017071663Peer reviewedFinal Published versio

Neurocognitive functioning in acute or early HIV infection

We examined neurocognitive functioning among persons with acute or early HIV infection (AEH) and hypothesized that the neurocognitive performance of AEH individuals would be intermediate between HIV seronegatives (HIV−) and those with chronic HIV infection. Comprehensive neurocognitive testing was accomplished with 39 AEH, 63 chronically HIV infected, and 38 HIV− participants. All AEH participants were HIV infected for less than 1 year. Average domain deficit scores were calculated in seven neurocognitive domains. HIV−, AEH, and chronically HIV infected groups were ranked from best (rank of 1) to worst (rank of 3) in each domain. All participants received detailed substance use, neuromedical, and psychiatric evaluations and HIV infected persons provided information on antiretroviral treatment and completed laboratory evaluations including plasma and CSF viral loads. A nonparametric test of ordered alternatives (Page test), and the appropriate nonparametric follow-up test, was used to evaluate level of neuropsychological (NP) functioning across and between groups. The median duration of infection for the AEH group was 16 weeks [interquartile range, IQR: 10.3–40.7] as compared to 4.9 years [2.8–11.1] in the chronic HIV group. A Page test using ranks of average scores in the seven neurocognitive domains showed a significant monotonic trend with the best neurocognitive functioning in the HIV− group (mean rank = 1.43), intermediate neurocognitive functioning in the AEH group (mean rank = 1.71), and the worst in the chronically HIV infected (mean rank = 2.86; L statistic = 94, p < 0.01); however, post-hoc testing comparing neurocognitive impairment of each group against each of the other groups showed that the chronically infected group was significantly different from both the HIV− and AEH groups on neurocognitive performance; the AEH group was statistically indistinguishable from the HIV− group. Regression models among HIV infected participants were unable to identify significant predictors of neurocognitive performance. Neurocognitive functioning was worst among persons with chronic HIV infection. Although a significant monotonic trend existed and patterns of the data suggest the AEH individuals may fall intermediate to HIV− and chronic participants, we were not able to statistically confirm this hypothesis

X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201

What works and why in the identification and referral of adults with comorbid obesity in primary care: a realist review

Primary care practitioners (PCPs) are well placed to identify individuals with obesity and weight‐related comorbidities and to refer them to weight management services (WMS), but this does not often happen in practice. In this realist review, we searched six databases for intervention studies targeted at PCPs to improve the identification and referral of adults with comorbid obesity. Realist analysis was used to identify context‐mechanism‐outcome (CMO) configurations across 30 included papers (reporting on 27 studies). Most studies used multiple intervention strategies, categorised into: (a) training, (b) tools to improve identification, (c) tools to improve ease of referral, (d) audit/feedback, (e) working in networks/quality circles, and (f) other. The realist synthesis identified 12 mechanisms through which interventions work to improve identification and referral, including increasing knowledge about obesity and awareness of and confidence in WMS among practitioners, improved communication and trust between practitioners and WMS, and higher priority given to weight management among primary care teams. The theory of “candidacy” (a person's eligibility for medical attention and intervention) provided a robust explanatory framework but required refinement: (a) to take account of the different services (primary care and weight management) that patients must navigate to access support; and (b) to acknowledge the importance of wider contextual factors

Brain structural and functional recovery following initiation of combination antiretroviral therapy

NeuroAIDS persists in the era of combination antiretroviral therapies. We describe here the recovery of brain structure and function following 6 months of therapy in a treatment-naive patient presenting with HIV-associated dementia. The patient’s neuropsychological test performance improved and his total brain volume increased by more than 5 %. Neuronal functional connectivity measured by magnetoencephalography changed from a pattern identical to that observed in other HIV-infected individuals to one that was indistinguishable from that of uninfected control subjects. These data suggest that at least some of the effects of HIV on the brain can be fully reversed with treatment

The Day-to-Day Impact of Urogenital Aging: Perspectives from Racially/Ethnically Diverse Women

Urogenital symptoms affect up to half of women after menopause, but their impact on women’s day-to-day functioning and wellbeing is poorly understood. Postmenopausal women aged 45 to 80 years reporting urogenital dryness, soreness, itching, or pain during sex were recruited to participate in in-depth focus groups to discuss the impact of their symptoms. Focus groups were homogenous with respect to race/ethnicity and stratified by age (for White or Black women) or language (for Latina women). Transcripts of sessions were analyzed according to grounded theory. Six focus groups were conducted, involving 44 women (16 White, 14 Black, 14 Latina). Five domains of functioning and wellbeing affected by symptoms were identified: sexual functioning, everyday activities, emotional wellbeing, body image, and interpersonal relations. For some participants, symptoms primarily affected their ability to have and enjoy sex, as well as be responsive to their partners. For others, symptoms interfered with everyday activities, such as exercising, toileting, or sleeping. Participants regarded their symptoms as a sign that they were getting old or their body was deteriorating; women also associated symptoms with a loss of womanhood or sexuality. Additionally, participants reported feeling depressed, embarrassed, and frustrated about their symptoms, and expressed reluctance to discuss them with friends, family, or health care providers. Urogenital symptoms can have a marked impact on sexual functioning, everyday activities, emotional wellbeing, body image, and interpersonal relations after menopause. Clinicians may need to question women actively about these symptoms, as many are reluctant to seek help for this problem