Changes in structural network topology correlate with severity of hallucinatory behavior in Parkinson's disease

Inefficient integration between bottom-up visual input and higher order visual processing regions is implicated in visual hallucinations in Parkinson's disease (PD). Here, we investigated white matter contributions to this perceptual imbalance hypothesis. Twenty-nine PD patients were assessed for hallucinatory behavior. Hallucination severity was correlated to connectivity strength of the network using the network-based statistic approach. The results showed that hallucination severity was associated with reduced connectivity within a subnetwork that included the majority of the diverse club. This network showed overall greater between-module scores compared with nodes not associated with hallucination severity. Reduced between-module connectivity in the lateral occipital cortex, insula, and pars orbitalis and decreased within-module connectivity in the prefrontal, somatosensory, and primary visual cortices were associated with hallucination severity. Conversely, hallucination severity was associated with increased between- and within-module connectivity in the orbitofrontal and temporal cortex, as well as regions comprising the dorsal attentional and default mode network. These results suggest that hallucination severity is associated with marked alterations in structural network topology with changes in participation along the perceptual hierarchy. This may result in the inefficient transfer of information that gives rise to hallucinations in PD. Author SummaryInefficient integration of information between external stimuli and internal perceptual predictions may lead to misperceptions or visual hallucinations in Parkinson's disease (PD). In this study, we show that hallucinatory behavior in PD patients is associated with marked alterations in structural network topology. Severity of hallucinatory behavior was associated with decreased connectivity in a large subnetwork that included the majority of the diverse club, nodes with a high number of between-module connections. Furthermore, changes in between-module connectivity were found across brain regions involved in visual processing, top-down prediction centers, and endogenous attention, including the occipital, orbitofrontal, and posterior cingulate cortex. Together, these findings suggest that impaired integration across different sides across different perceptual processing regions may result in inefficient transfer of information

A standardised nutritional drink as a test meal for the 13 C mixed triglyceride breath test for pancreatic exocrine insufficiency:A randomised, two-arm crossover comparative study

BACKGROUND: The 13 C mixed triglyceride breath test (13 C MTGT) is a diagnostic test for pancreatic exocrine insufficiency (PEI). It is poorly standardised with much heterogeneity of the test meal, the commonest being toast and butter. A standardised oral nutritional supplement that could be easily transported, stored and made up would be valuable for making this test accessible outside of specialist centres.METHODS: A prospective, randomised, two-arm crossover study of different test meals was carried out in 14 healthy controls. The 13 C MTGT was performed in identical conditions on two separate days. Two test meals were given in random order, either standard (toast and butter) or novel (oral nutritional supplement), with 250 mg of 13 C-labelled mixed triglyceride incorporated. Breath samples were taken postprandially to calculate cumulative percentage dose recovery (cPDR) of 13 C at 6 h.RESULTS: All 14 participants completed both arms of the study with no protocol deviations. The mean cPDR was 39.39% (standard deviation [SD] 5.19) for the standard test meal and 39.93% (SD 5.20) for the novel test meal. A one-way repeated measures analysis of variance (ANOVA) found no significant difference in cPDR between the two meals, F(1, 13) = 0.18, p = 0.68 (minimum detectable difference of 0.81 at 80% power).CONCLUSION: This study demonstrates that a standardised oral nutritional supplement can be used without compromising 13 C recovery. Using this test meal provides a standardised dietary stimulus to the pancreas, avoiding possible variation in quantity of dietary components with other test meals. Further, the ease of use of this method would help establish the 13 C MTGT test more widely.</p

CMB power spectrum parameter degeneracies in the era of precision cosmology

Cosmological parameter constraints from the CMB power spectra alone suffer several well-known degeneracies. These degeneracies can be broken by numerical artefacts and also a variety of physical effects that become quantitatively important with high-accuracy data e.g. from the Planck satellite. We study degeneracies in models with flat and non-flat spatial sections, non-trivial dark energy and massive neutrinos, and investigate the importance of various physical degeneracy-breaking effects. We test the CAMB power spectrum code for numerical accuracy, and demonstrate that the numerical calculations are accurate enough for degeneracies to be broken mainly by true physical effects (the integrated Sachs-Wolfe effect, CMB lensing and geometrical and other effects through recombination) rather than numerical artefacts. We quantify the impact of CMB lensing on the power spectra, which inevitably provides degeneracy-breaking information even without using information in the non-Gaussianity. Finally we check the numerical accuracy of sample-based parameter constraints using CAMB and CosmoMC. In an appendix we document recent changes to CAMB's numerical treatment of massive neutrino perturbations, which are tested along with other recent improvements by our degeneracy exploration results.Comment: 27 pages, 28 figures. Latest CAMB version available from http://camb.info/. Reduced number of figures, plot legend corrected and minor edits to match published versio

Higher order intentionality tasks are cognitively more demanding

A central assumption that underpins much of the discussion of the role played by social cognition in brain evolution is that social cognition is unusually cognitively demanding. This assumption has never been tested. Here, we use a task in which participants read stories and then answered questions about the stories in a behavioural experiment (39 participants) and an fMRI experiment (17 participants) to show that mentalising requires more time for responses than factual memory of a matched complexity and also that higher orders of mentalising are disproportionately more demanding and require the recruitment of more neurons in brain regions known to be associated with theory of mind, including insula, posterior STS, temporal pole and cerebellum. These results have significant implications both for models of brain function and for models of brain evolution

Emission-angle and polarization-rotation effects in the lensed CMB

Lensing of the CMB is an important effect, and is usually modelled by remapping the unlensed CMB fields by a lensing deflection. However the lensing deflections also change the photon path so that the emission angle is no longer orthogonal to the background last-scattering surface. We give the first calculation of the emission-angle corrections to the standard lensing approximation from dipole (Doppler) sources for temperature and quadrupole sources for temperature and polarization. We show that while the corrections are negligible for the temperature and E-mode polarization, additional large-scale B-modes are produced with a white spectrum that dominates those from post-Born field rotation (curl lensing). On large scales about one percent of the total lensing-induced B-mode amplitude is expected to be due to this effect. However, the photon emission angle does remain orthogonal to the perturbed last-scattering surface due to time delay, and half of the large-scale emission-angle B modes cancel with B modes from time delay to give a total contribution of about half a percent. While not important for planned observations, the signal could ultimately limit the ability of delensing to reveal low amplitudes of primordial gravitational waves. We also derive the rotation of polarization due to multiple deflections between emission and observation. The rotation angle is of quadratic order in the deflection angle, and hence negligibly small: polarization typically rotates by less than an arcsecond, orders of magnitude less than a small-scale image rotates due to post-Born field rotation (which is quadratic in the shear). The field-rotation B modes dominate the other effects on small scales.AL acknowledges support from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement No. [616170], and AL and AC from the Science and Technology Facilities Council [grant numbers ST/L000652/1 and ST/N000927/1, respectively]. AH is supported by a United Kingdom Space Agency Euclid grant, and an STFC Consolidated Grant

Suicide Screening in Primary Care: Use of an Electronic Screener to Assess Suicidality and Improve Provider Follow-Up for Adolescents

Purpose The purpose of this study was to assess the feasibility of using an existing computer decision support system to screen adolescent patients for suicidality and provide follow-up guidance to clinicians in a primary care setting. Predictors of patient endorsement of suicidality and provider documentation of follow-up were examined. Methods A prospective cohort study was conducted to examine the implementation of a CDSS that screened adolescent patients for suicidality and provided follow-up recommendations to providers. The intervention was implemented for patients aged 12–20 years in two primary care clinics in Indianapolis, Indiana. Results The sample included 2,134 adolescent patients (51% female; 60% black; mean age = 14.6 years [standard deviation = 2.1]). Just over 6% of patients screened positive for suicidality. A positive endorsement of suicidality was more common among patients who were female, depressed, and seen by an adolescent−medicine board-certified provider as opposed to general pediatric provider. Providers documented follow-up action for 83% of patients who screened positive for suicidality. Documentation of follow-up action was correlated with clinic site and Hispanic race. The majority of patients who endorsed suicidality (71%) were deemed not actively suicidal after assessment by their provider. Conclusions Incorporating adolescent suicide screening and provider follow-up guidance into an existing computer decision support system in primary care is feasible and well utilized by providers. Female gender and depressive symptoms are consistently associated with suicidality among adolescents, although not all suicidal adolescents are depressed. Universal use of a multi-item suicide screener that assesses recency might more effectively identify suicidal adolescents

Observational study of the association of first insulin type in uncontrolled type 2 diabetes with macrovascular and microvascular disease

&lt;p&gt;Aims: To compare the risk of vascular disease, HbA1c and weight change, between first prescribed insulins in people with type 2 diabetes.&lt;/p&gt; &lt;p&gt;Methods: People included in THIN United Kingdom primary care record database who began insulin (2000–2007) after poor control on oral glucose-lowering agents (OGLD) were grouped by the number of OGLDs in their treatment regimen immediately before starting insulin (n = 3,485). Within OGLD group, Cox regression compared macrovascular (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and microvascular disease (peripheral neuropathy, nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A1c (HbA1c) and weight change.&lt;/p&gt; &lt;p&gt;Results: Mean follow-up was 3.6 years. Rates of incident macrovascular events were similar when basal insulin was compared to pre-mix or NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH 1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32, 1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus basal after 3 OGLDs, adjusted hazard ratio1.87 (1.04, 3.36), was not seen after two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs, weight increase was less with basal compared with pre-mix. After three OGLDs, mean HbA1c had reduced less in basal versus pre-mix or NPH at 6–8 and at 9–11 months, and versus pre-mix at 12–14 months.&lt;/p&gt; &lt;p&gt;Conclusion: We found no difference in the risk of macrovascular events between first insulins in the medium term when started during poor glycaemia control. The increased risk of microvascular events with NPH warrants further study. In certain groups, first use of basal insulin was associated with less gain in weight and decrease in HbA1c compared to other insulins.&lt;/p&gt

'Who do "they" cheer for?' Cricket, diaspora, hybridity and divided loyalties amongst British Asians

This article explores the relationship between British Asians' sense of nationhood, citizenship, ethnicity and some of their manifestations in relation to sports fandom: specifically in terms of how cricket is used as a means of articulating diasporic British Asian identities. Norman Tebbit's 'cricket test' is at the forefront of this article to tease out the complexities of being British Asian in terms of supporting the English national cricket team. The first part of the article locates Tebbit's 'cricket test' within the wider discourse of multiculturalism. The analysis then moves to focus on the discourse of sports fandom and the concept of 'home team advantage' arguing that sports venues represent significant sites for nationalist and cultural expression due to their connection with national history. The article highlights how supporting 'Anyone but England', thereby rejecting ethnically exclusive notions of 'Englishness' and 'Britishness', continues to be a definer of British Asians' cultural identities. The final section situates these trends within the discourse of hybridity and argues that sporting allegiances are often separate from considerations of national identity and citizenship. Rather than placing British Asians in an either/or situation, viewing British 'Asianness' in hybrid terms enables them to celebrate their traditions and histories, whilst also being proud of their British citizenship. © The Author(s) 2011

Sparrows can't sing : East End kith and kinship in the 1960s

Sparrows Can’t Sing (1963) was the only feature film directed by the late and much lamented Joan Littlewood. Set and filmed in the East End, where she worked for many years, the film deserves more attention than it has hitherto received. Littlewood’s career spanned documentary (radio recordings made with Ewan MacColl in the North of England in the 1930s) to directing for the stage and the running of the Theatre Royal in London’s Stratford East, often selecting material which aroused memories in local audiences (Leach 2006: 142). Many of the actors trained in her Theatre Workshop subsequently became better known for their appearances on film and television. Littlewood herself directed hardly any material for the screen: Sparrows Can’t Sing and a 1964 series of television commercials for the British Egg Marketing Board, starring Theatre Workshop’s Avis Bunnage, were rare excursions into an area of practice which she found constraining and unamenable (Gable 1980: 32). The hybridity and singularity of Littlewood’s feature may answer, in some degree, for its subsequent neglect. However, Sparrows Can’t Sing makes a significant contribution to a group of films made in Britain in the 1960s which comment generally on changes in the urban and social fabric. It is especially worthy of consideration, I shall argue, for the use which Littlewood made of a particular community’s attitudes – sentimental and critical – to such changes and for its amalgamation of an attachment to documentary techniques (recording an aural landscape on location) with a preference for nonnaturalistic delivery in performance

Probing the neutrino mass hierarchy with CMB weak lensing

We forecast constraints on cosmological parameters with primary CMB anisotropy information and weak lensing reconstruction with a future post-Planck CMB experiment, the Cosmic Origins Explorer (COrE), using oscillation data on the neutrino mass splittings as prior information. Our MCMC simulations in flat models with a non-evolving equation-of-state of dark energy w give typical 68% upper bounds on the total neutrino mass of 0.136 eV and 0.098 eV for the inverted and normal hierarchies respectively, assuming the total summed mass is close to the minimum allowed by the oscillation data for the respective hierarchies (0.10 eV and 0.06 eV). Including information from future baryon acoustic oscillation measurements with the complete BOSS, Type 1a supernovae distance moduli from WFIRST, and a realistic prior on the Hubble constant, these upper limits shrink to 0.118 eV and 0.080 eV for the inverted and normal hierarchies, respectively. Addition of these distance priors also yields percent-level constraints on w. We find tension between our MCMC results and the results of a Fisher matrix analysis, most likely due to a strong geometric degeneracy between the total neutrino mass, the Hubble constant, and w in the unlensed CMB power spectra. If the minimal-mass, normal hierarchy were realised in nature, the inverted hierarchy should be disfavoured by the full data combination at typically greater than the 2-sigma level. For the minimal-mass inverted hierarchy, we compute the Bayes' factor between the two hierarchies for various combinations of our forecast datasets, and find that the future probes considered here should be able to provide `strong' evidence (odds ratio 12:1) for the inverted hierarchy. Finally, we consider potential biases of the other cosmological parameters from assuming the wrong hierarchy and find that all biases on the parameters are below their 1-sigma marginalised errors.Comment: 16 pages, 13 figures; minor changes to match the published version, references adde