Using Actiwatch to monitor circadian rhythm disturbance in Huntington' disease: A cautionary note

Huntington's disease (HD) is an inherited neurodegenerative disorder that is well recognised as producing progressive deterioration of motor function, including dyskinetic movements, as well as deterioration of cognition and ability to carry out activities of daily living. However, individuals with HD commonly suffer from a wide range of additional symptoms, including weight loss and sleep disturbance, possibly due to disruption of circadian rhythmicity. Disrupted circadian rhythms have been reported in mice models of HD and in humans with HD. One way of assessing an individual's circadian rhythmicity in a community setting is to monitor their sleep/wake cycles, and a convenient method for recording periods of wakefulness and sleep is to use accelerometers to discriminate between varied activity levels (including sleep) during daily life. Here we used Actiwatch® Activity monitors alongside ambulatory EEG and sleep diaries to record wake/sleep patterns in people with HD and normal volunteers. We report that periods of wakefulness during the night, as detected by activity monitors, agreed poorly with EEG recordings in HD subjects, and unsurprisingly sleep diary findings showed poor agreement with both EEG recordings and activity monitor derived sleep periods. One explanation for this is the occurrence of 'break through' involuntary movements during sleep in the HD patients, which are incorrectly assessed as wakeful periods by the activity monitor algorithms. Thus, care needs to be taken when using activity monitors to assess circadian activity in individuals with movement disorders

Better long-term speech outcomes in stroke survivors who received early clinical speech and language therapy: What's driving recovery?

Establishing whether speech and language therapy after stroke has beneficial effects on speaking ability is challenging because of the need to control for multiple non-therapy factors known to influence recovery. We investigated how speaking ability at three time points post-stroke differed in patients who received varying amounts of clinical therapy in the first month post-stroke. In contrast to prior studies, we factored out variance from: initial severity of speaking impairment, amount of later therapy, and left and right hemisphere lesion size and site. We found that speaking ability at one month post-stroke was significantly better in patients who received early therapy (n = 79), versus those who did not (n = 64), and the number of hours of early therapy was positively related to recovery at one year post-stroke. We offer two non-mutually exclusive interpretations of these data: (1) patients may benefit from the early provision of self-management strategies; (2) therapy is more likely to be provided to patients who have a better chance of recovery (e.g., poor physical and/or mental health may impact suitability for therapy and chance of recovery). Both interpretations have implications for future studies aiming to predict individual patients' speech outcomes after stroke, and their response to therapy

Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n= 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. IMPORTANCE The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable

Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. IMPORTANCE The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable

Structure and variability of the Denmark Strait Overflow: Model and observations

We report on a combined modeling and observational effort to understand the Denmark Strait Overflow (DSO). Four cruises over the course of 3 years mapped hydrographic properties and velocity fields with high spatial resolution. The observations reveal the mean path of the dense water, as well as the presence of strong barotropic flows, energetic variability, and strong bottom friction and entrainment. A regional sigma coordinate numerical model of interbasin exchange using realistic bottom topography and an overflow forced only by an upstream reservoir of dense fluid is compared with the observations and used to further investigate these processes. The model successfully reproduces the volume transport of dense water at the sill, as well as the 1000-m descent of the dense water in the first 200 km from the sill and the intense eddies generated at 1–3 day intervals. Hydraulic control of the mean flow is indicated by a region supercritical to long gravity waves in the dense layer located approximately 100 km downstream of the sill in both model and observations. In addition, despite the differences in surface forcing, both model and observations exhibit similar transitions from mostly barotropic flow at the sill to a bottom-trapped baroclinic flow downstream, indicating the dominant role of the overflow in determining the full water column dynamics

Planetary Transits of the Trans-Atlantic Exoplanet Survey- Candidate TrES-1b

The AAVSO compiled 10,560 CCD observations of the suspected exoplanet transit object TrES-1b covering seven complete transit windows, three windows of partial coverage, and coverage of baseline non-transit periods. Visual inspection of the light curves reveals the presence of slight humps at the egress points of some transits. A boot strap Monte Carlo simulation was applied to the data to confirm that the humps exist to a statistically significant degree. However, it does not rule out systemic effects which will be tested with campaigns in the 2005 observing season

Impact of paracetamol impurities on face properties : investigating the surface of single crystals using TOF-SIMS

Understanding the mechanism of interaction between pharmaceutical molecules (APIs) and impurities on crystal surfaces is a key concept in understanding purification and for the design of pharmaceutical crystallization processes. Several techniques may be used to study crystal surface properties, such as scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), which provide detailed imaging and elemental surface characterization. Time of flight secondary ion mass spectrometry (TOF-SIMS) is valuable in determining molecular identity and distribution. By combining TOF-SIMS, SEM, and optical (OM) and Raman microscopies, we can evaluate the usefulness of TOF-SIMS as a surface characterization technique for pharmaceutical crystals. 4-Nitrophenol has been selected as an impurity that can be incorporated during crystallization of acetaminophen (paracetamol). This study explores the distribution of impurity and its concentration on the different crystal faces of samples obtained by crystallization over a range of impurity loadings and supersaturation conditions. Raman maps of paracetamol single crystal faces were analyzed using the characteristic Raman peak intensity of 4-nitrophenol to identify regions where it accumulated; Raman maps of three single crystals produced in the presence of 4-nitrophenol using different crystallization procedures highlight how it can be difficult to detect very low concentrations of similar chemical species. In contrast, the 4-nitrophenol monoisotopic mass obtained via TOF-SIMS was shown to be detectable in all the three single crystals produced. This indicates that TOF-SIMS can be a valuable technique for single crystal impurity distribution mapping even when the impurity concentration is very low

Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

<p>Abstract</p> <p>Background</p> <p>Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients.</p> <p>Methods</p> <p>In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPα and sAPPβ), amyloid beta fragment 1-42 (Aβ_1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease.</p> <p>Results</p> <p>CSF sAPPα and sAPPβ concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Aβ_1-42in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections.</p> <p>Conclusions</p> <p>Parallel reductions of CSF sAPPα and sAPPβ in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.</p

Introductory programming: a systematic literature review

As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research