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Background: Closed-loop artificial pancreas device (APD) systems are externally worn medical devices that are being developed to enable people with type 1 diabetes to regulate their blood glucose levels in a more automated way. The innovative concept of this emerging technology is that hands-free, continuous, glycemic control can be achieved by using digital communication technology and advanced computer algorithms. Methods: A horizon scanning review of this field was conducted using online sources of intelligence to identify systems in development. The systems were classified into subtypes according to their level of automation, the hormonal and glycemic control approaches used, and their research setting. Results: Eighteen closed-loop APD systems were identified. All were being tested in clinical trials prior to potential commercialization. Six were being studied in the home setting, 5 in outpatient settings, and 7 in inpatient settings. It is estimated that 2 systems may become commercially available in the EU by the end of 2016, 1 during 2017, and 2 more in 2018. Conclusions: There are around 18 closed-loop APD systems progressing through early stages of clinical development. Only a few of these are currently in phase 3 trials and in settings that replicate real life.

The goal of this study was to compare five actigraphy scoring methods in a sample of 18 remitted patients with bipolar disorder. Actigraphy records were processed using five different scoring methods relying on the sleep diary; the event-marker; the software-provided automatic algorithm; the automatic algorithm supplemented by the event-marker; visual inspection (VI) only. The Algorithm and the VI methods differed from the other methods for many actigraphy parameters of interest. Particularly, the Algorithm method yielded longer sleep duration, and the VI method yielded shorter sleep latency compared to the others methods. The present findings provide guidance for the selection of signal processing method based on sleep parameters of interest, time-cue sources and availability, and related scoring time costs for the study.

Background This study compared diurnal variation in mood and regional cerebral metabolic rate of glucose (rCMRglc) in depressed and healthy subjects. Methods Depressed and healthy subjects were investigated using [ 18 F]-fluoro-deoxyglucose positron emission tomography scans during morning and evening wakefulness. All subjects completed subjective mood ratings at both times of day. Statistical parametric mapping was used to compare rCMRglc between the two groups across time of day. Results Depressed patients showed evening mood improvements compared with healthy subjects. Compared with healthy subjects, depressed patients showed smaller increases in rCMRglc during evening relative to morning wakefulness in lingual and fusiform cortices, midbrain reticular formation, and locus coeruleus and greater increases in rCMRglc in parietal and temporal cortices. Depressed patients had hypermetabolism in limbic-paralimbic regions and hypometabolism in frontal and parietal cortex at both times of day compared with healthy subjects. Conclusions Variation in rCMRglc differs across times of day in depressed and healthy subjects. In depressed patients, evening mood improvements were associated with increased metabolic activity in ventral limbic-paralimbic, parietal, temporal, and frontal regions and in the cerebellum. This increased metabolic pattern during evening wakefulness may reflect partial normalization of primary and compensatory neural systems involved in affect production and regulation.

Professional identity formation is important for new recruits to training programmes. The integration of the accumulation of knowledge and assessment is a key aspect in its acquisition. This study assessed this interaction in Public Health Training in one English region.Semi-structured interviews were held with 15 registrars from the West Midlands Public Health Training Programme. Pre-interview questionnaires gathered background information. A thematic content analysis approach was taken.There was a lack of integration between academic and workplace learning, the professional examination process and professional identity development. Registrars considered sitting the examination and their workplace learning as two parallel processes. Passing the examination was considered a key part in the early development of a professional identity but this was replaced by the opinions of others by the third year of training. Having a Masters' in Public Health was less important but played a different role in their perceived acceptance by the wider Public Health workforce.The lack of integration between assessment and learning seemed to have a detrimental effect on professional identity development. A review of how these two aspects might combine in a more positive manner is needed.

To assess whether daytime naps negatively impact nocturnal sleep.Longitudinal, prospective cohort design.161 pregnant women recruited and evaluated in early gestation (10-20 weeks).Daily sleep information was collected in three 2-week periods (10-12, 14-16, and 18-20 weeks gestation) with a daily sleep diary and an actigraph. The average number of naps, as well as the average length of each nap, were calculated from sleep diaries. Women were categorized first as non nappers (0 naps/2-week period), moderate nappers (1-3 naps/2-week period), or frequent nappers (≥ 4 naps/2-week period). Then, based on the average nap length, they were categorized as short (90 min) or long (≥ 90 min) nappers. Nocturnal sleep parameters included SOL, WASO, SE, and TST. SAS procedure MIXED was used for modeling the main effects of nap group and time, and time by nap group interactions. Women who took naps had a decrease in diary-assessed nocturnal TST, but not actigraphy-assessed TST. This observation was group- and time-specific. There were no other group differences. Women who napped ≥ 90 min had poorer diary-assessed SE and lower diary-assessed TST than those who took shorter naps. Length of nap was not associated with any other sleep measures.The number of daytime naps have minimal impact on nocturnal sleep parameters; however, long nappers did exhibit modestly impaired sleep continuity and sleep quality. Overall, we propose that daytime naps provide a beneficial countermeasure to the sleep disruption commonly reported by pregnant women. This may be clinically beneficial given that sleep continuity and quality are important correlates of pregnancy outcomes.A commentary on this article appears in this issue on page 593.

Changes in undergraduate medical training mean that students have direct patient contact from an early stage of their training. This study aimed to assess the knowledge of third-year medical students at the University of Birmingham Medical School, UK on infection control policy and procedures. A semi-structured questionnaire was distributed to medical students. Out of 322 students, 156 returned completed questionnaires (48%). Results showed that 58% of medical students did not know the correct indications for using alcoholic hand gel, 35% did not know the correct use of gloves, and 50% did not know the exclusion period after an episode of diarrhoea and vomiting. Sixty-four percent of medical students reported formal teaching on hand hygiene, 12% reported informal teaching, 19% reported both types of teaching and 5% reported no hand hygiene teaching at all. Forty-nine percent of medical students thought that there was insufficient emphasis on infection control in their course. These results raised concerns about medical students' knowledge about infection control. The University is currently reviewing the need for a more structured model for the teaching and assessment of infection control.

This pilot study compared daytime symptom ratings in primary insomniacs (n = 7) and age-matched controls (n = 8). Participants completed sleep diaries and rated their daytime symptoms using a Daytime Symptom Diary (DSD) 4 times per day for 1 week. DSD responses were collapsed into 4 domains: mood, subjective alertness, energy, and concentration. The level and variability of DSD domains, and correlations between the domains and sleep diary characteristics, were examined. Significant Group x Time of Day interactions were observed in values for each DSD domain, with the most consistent group differences occurring in the morning. Coefficients of variation for DSD domains were greater in the insomnia group. Frequent measures of daytime symptoms may be useful outcomes in insomnia studies.

This study sought to clarify the effects of bupropion SR on anterior paralimbic function in depressed patients by studying changes in the activation of these structures from waking to REM sleep both before and after treatment. Twelve depressed patients underwent concurrent EEG sleep studies and [18F]fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) scans during waking and during their second REM period of sleep before and after treatment with bupropion SR. Nine subjects completed pre- and post-treatment waking PET studies. Five subjects completed pre- and post-treatment waking and REM sleep PET studies. Bupropion SR treatment did not suppress electrophysiologic measures of REM sleep, nor did it alter an indirect measure of global metabolism during either waking or REM sleep. Bupropion SR treatment reversed the previously observed deficit in anterior cingulate, medial prefrontal cortex and right anterior insula activation from waking to REM sleep. In secondary analyses, this effect was related to a reduction in waking relative metabolism in these structures following treatment in the absence of a significant effect on REM sleep relative metabolism. The implications of these findings for the relative importance of anterior paralimbic function in REM sleep in depression and for the differential effects of anti-depressant treatment on brain function during waking vs. REM sleep are discussed.

The proportion of culture-confirmed tuberculosis (TB) cases in Birmingham had gradually decreased to less than 65% in 2008. Reasons for this were unclear, therefore this study assessed diagnostic methods used for confirming TB and reviewed factors involved in positive culture.A cross-sectional study was carried out. A list of notified TB cases for Birmingham in those aged 16 y and over in 2009 was collated. Where no positive culture was recorded, further data were collected from hospital databases and case notes.Of 449 TB cases, 419 (93%) had samples taken for culture testing. Of all cases, 309 (69%) were confirmed by culture testing; of those receiving culture testing, 73% were confirmed. Pulmonary TB was identified as a predictor of positive culture in both the unadjusted and adjusted analyses: odds ratio (OR) 2.05, 95% confidence interval (CI) 1.32-3.19, and OR 2.32, 95% CI 1.29-4.17, respectively. Gender, age, ethnicity, UK born, and treatment delay were not significantly associated with positive culture. Of 140 cases not confirmed by culture, 129 (92%) had their diagnosis supported by at least one other test.The vast majority of TB cases had microbiological specimens taken to help confirm the disease. Furthermore, culture confirmation rates in Birmingham were meeting national targets in 2009. However culture confirmation rates were significantly lower in extrapulmonary TB, therefore further work is suggested in this group. The role of other investigations (e.g. interferon-gamma release assay (IGRA), Mantoux) is unclear. Further collaboration between clinicians, histopathologists, and microbiologists is advised to ensure samples are sent appropriately and culture confirmation is optimized.

BACKGROUND: We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK. METHODOLOGY/PRINCIPAL FINDINGS: Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the "Mercian" strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95%CI = 4.56-17.87, p65 years old (OR = 0.25, 95% CI = 0.09-0.67, p < 0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95% CI = 2.00-46.78, p < 0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95%CI = 1.45-27.02, p = .01) were observed as social risk factors for infection. CONCLUSIONS/SIGNIFICANCE: The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain.

We examined MMR vaccine uptake among ethnic groups in Birmingham, UK between 1994 and 2000, a period incorporating adverse MMR vaccine publicity. From 1994 to 2000 overall uptake: (1) fell significantly from 91.1% in 1994 to 89.8% (chi(2) for trend p0.001) in 2000, (2) in Asian children significantly increased (chi(2) for trend p0.001), and (3) in White children significantly decreased (chi(2) for trend p0.001). Differences between ethnic groups with the highest (Asian) and the lowest (Black Caribbean) uptake rates increased from 2.1% in 1994 (p=ns) to 6.8% in 2000 (p0.001). This study suggests underlying ethnic inequalities in MMR vaccine uptake and differential response to adverse vaccine publicity.

Study objectives The mechanisms that maintain wakefulness across the day, in the face in increasing sleep drive, are largely unknown. The goal of this pilot study was to examine regional relative brain glucose metabolism during morning and evening wakefulness in healthy humans. Design [18F]-fluorodeoxyglucose positron emission tomography scans were conducted during quiet wakefulness in the morning and in the evening. Statistical parametric mapping was used to compare relative regional glucose metabolism during the 2 scans. Subjects also completed subjective ratings of alertness. Setting University of Pittsburgh General Clinical Research Center and Positron Emission Tomography Facility. Patients or participants Thirteen healthy adults (10 women, 3 men; mean age, 37 years) Interventions None. Measurements and results Relative regional glucose metabolism was significantly higher in the evening than in the morning in a large cluster of midline and brainstem structures. Volumes of interest centered on the pontine reticular formation, midbrain reticular formation, midbrain raphe, locus coeruleus, and posterior hypothalamus also showed higher relative metabolism in the evening than in the morning. Relative glucose metabolism was significantly lower in the evening than in the morning in clusters that included structures in the right temporal cortex and occipital lobe, including cuneus and medial occipital gyrus. Conclusions Evening wakefulness is associated with increased relative metabolism in brainstem and hypothalamic arousal systems and decreased relative metabolism in posterior cortical regions. These patterns may reflect input from the circadian timing system to promote wakefulness, and/or the effects of increasing homeostatic sleep drive.

In depressed patients, REM density, or the number of rapid eye movements (REMs) per minute of REM sleep, is a correlate of depression severity and clinical outcomes. We investigated the functional neuroanatomical correlates of average REM counts (RC), an automated analog of REM density, in depression. Thirteen medication-free depressed patients underwent all night polysomnography and positron emission tomography (PET) scans using [(18)F]fluoro-2-deoxy-d-glucose ([(18)F] FDG) during REM sleep. Regression analyses were conducted with Statistical Parametric Mapping (SPM-99). Average RC significantly and positively correlated with relative regional cerebral metabolic rate of glucose (rCMRglc) bilaterally in the striate cortex, the posterior parietal cortices, and in the medial and ventrolateral prefrontal cortices. Average RC were negatively correlated with rCMRglc in areas corresponding bilaterally to the lateral occipital cortex, cuneus, temporal cortices, and parahippocampal gyri. The areas where average RC was positively correlated with rCMRglc appear to constitute a diffuse cortical system involved in the regulation of emotion-induced arousal. The observed pattern of correlations suggests that average RC may be a marker of hypofrontality during REM sleep in depressed patients.