High-level cognition during story listening is reflected in high-order dynamic correlations in neural activity patterns

Our thoughts arise from coordinated patterns of interactions between brain structures that change with our ongoing experiences. High-order dynamic correlations in neural activity patterns reflect different subgraphs of the brain’s functional connectome that display homologous lower-level dynamic correlations. Here we test the hypothesis that high-level cognition is reflected in high-order dynamic correlations in brain activity patterns. We develop an approach to estimating high-order dynamic correlations in timeseries data, and we apply the approach to neuroimaging data collected as human participants either listen to a ten-minute story or listen to a temporally scrambled version of the story. We train across-participant pattern classifiers to decode (in held-out data) when in the session each neural activity snapshot was collected. We find that classifiers trained to decode from high-order dynamic correlations yield the best performance on data collected as participants listened to the (unscrambled) story. By contrast, classifiers trained to decode data from scrambled versions of the story yielded the best performance when they were trained using first-order dynamic correlations or non-correlational activity patterns. We suggest that as our thoughts become more complex, they are reflected in higher-order patterns of dynamic network interactions throughout the brain

Trends and risk factors for death and excess all-cause mortality among notified tuberculosis patients in the UK: an analysis of surveillance data.

INTRODUCTION: In the UK, several hundred patients notified with tuberculosis (TB) die every year. The aim of this article is to describe trends in deaths among notified TB patients, explore risk factors associated with death and compare all-cause mortality in TB patients with age-specific mortality rates in the general UK population. METHODS: We used 2001-2014 data from UK national TB surveillance to explore trends and risk factors for death, and population mortality data to compare age-specific death rates among notified TB patients with annual death rates in the UK general population. RESULTS: The proportion of TB patients in the UK who died each year declined steadily from 7.1% in 2002 to 5.5% in 2014. One in five patients (21.3%) was diagnosed with TB post-mortem. Where information was available, almost half of the deaths occurred within 2 months of starting treatment. Risk factors for death included demographic, disease-specific and social risk factors. Age had by far the largest effect, with patients aged ≥80 years having a 70 times increased risk of death compared with those aged <15 years. In contrast, excess mortality determined by incidence ratios comparing all-cause mortality among TB patients with that of the general population was highest among children and the working-age population (15-64 years old). CONCLUSIONS: Efforts to control TB and improve diagnosis and treatment outcomes in the UK need to be sustained. Control efforts need to focus on socially deprived and vulnerable groups. There is a need for further in-depth analysis of deaths of TB patients in the UK to identify potentially preventable factors

Using Social Networking Sites for Communicable Disease Control: Innovative Contact Tracing or Breach of Confidentiality?

Social media applications such as Twitter, YouTube and Facebook have attained huge popularity, with more than three billion people and organizations predicted to have a social networking account by 2015. Social media offers a rapid avenue of communication with the public and has potential benefits for communicable disease control and surveillance. However, its application in everyday public health practice raises a number of important issues around confidentiality and autonomy. We report here a case from local level health protection where the friend of an individual with meningococcal septicaemia used a social networking site to notify potential contacts

Delirium, frailty and mortality:interactions in a prospective study of hospitalized older people

AbstractBackgroundIt is unknown if the association between delirium and mortality is consistent for individuals across the whole range of health states. A bimodal relationship has been proposed, where delirium is particularly adverse for those with underlying frailty, but may have a smaller effect (perhaps even protective) if it is an early indicator of acute illness in fitter people. We investigated the impact of delirium on mortality in a cohort simultaneously evaluated for frailty.MethodsWe undertook an exploratory analysis of a cohort of consecutive acute medical admissions aged ≥70. Delirium on admission was ascertained by psychiatrists. A Frailty Index (FI) was derived according to a standard approach. Deaths were notified from linked national mortality statistics. Cox regression was used to estimate associations between delirium, frailty and their interactions on mortality.ResultsThe sample consisted of 710 individuals. Both delirium and frailty were independently associated with increased mortality rates (delirium: HR 2.4, 95%CI 1.8-3.3, p&lt;0.01; frailty (per SD): HR 3.5, 95%CI 1.2-9.9, p=0.02). Estimating the effect of delirium in tertiles of FI, mortality was greatest in the lowest tertile: tertile 1 HR 3.4 (95%CI 2.1-5.6); tertile 2 HR 2.7 (95%CI 1.5-4.6); tertile 3 HR 1.9 (95% CI 1.2-3.0).ConclusionWhile delirium and frailty contribute to mortality, the overall impact of delirium on admission appears to be greater at lower levels of frailty. In contrast to the hypothesis that there is a bimodal distribution for mortality, delirium appears to be particularly adverse when precipitated in fitter individuals.</jats:sec

Assessing the reliability of uptake and elimination kinetics modelling approaches for estimating bioconcentration factors in the freshwater invertebrate, Gammarus pulex

This study considers whether the current standard toxicokinetic methods are an accurate and applicable assessment of xenobiotic exposure in an aquatic freshwater invertebrate. An in vivo exposure examined the uptake and elimination kinetics for eight pharmaceutical compounds in the amphipod crustacean, Gammarus pulex by measuring their concentrations in both biological material and in the exposure medium over a 96 h period. Selected pharmaceuticals included two anti-inflammatories (diclofenac and ibuprofen), two beta-blockers (propranolol and metoprolol), an anti-depressant (imipramine), an anti-histamine (ranitidine) and two beta-agonists (formoterol and terbutaline). Kinetic bioconcentration factors (BCFs) for the selected pharmaceuticals were derived from a first-order one-compartment model using either the simultaneous or sequential modelling methods. Using the simultaneous method for parameter estimation, BCF values ranged from 12 to 212. In contrast, the sequential method for parameter estimation resulted in bioconcentration factors ranging from 19 to 4533. Observed toxicokinetic plots showed statistically significant lack-of-fits and further interrogation of the models revealed a decreasing trend in the uptake rate constant over time for rantidine, diclofenac, imipramine, metoprolol, formoterol and terbutaline. Previous published toxicokinetic data for 14 organic micro-pollutants were also assessed and similar trends were identified to those observed in this study. The decreasing trend of the uptake rate constant over time highlights the need to interpret modelled data more comprehensively to ensure uncertainties associated with uptake and elimination parameters for determining bioconcentration factors are minimised

Hepatitis E Outbreak on Cruise Ship

The outbreak was probably foodborne

An evaluation of tuberculosis contact investigations against national standards.

BACKGROUND: Contact tracing is a key element in England's 2015 collaborative TB strategy, although proposed indicators of successful contact tracing remain undescribed. METHODS: We conducted descriptive and multivariable analyses of contact tracing of TB cases in London between 1 July 2012 and 31 December 2015 using cohort review data from London's TB Register, identifying characteristics associated with improved indicators and yield. RESULTS: Of the pulmonary TB cases notified, 60% (2716/4561) had sufficient information for inclusion. Of these, 91% (2481/2716) had at least 1 contact (median: 4/case (IQR: 2-6)) identified, with 86% (10 251/11 981) of these contacts evaluated. 4.1% (177/4328), 1.3% (45/3421) and 0.70% (51/7264) of evaluated contacts of pulmonary smear-positive, pulmonary smear-negative and non-pulmonary cases, respectively, had active disease. Cases who were former prisoners or male were less likely to have at least one contact identified than those never imprisoned or female, respectively. Cases diagnosed at clinics with more directly observed therapy or social workers were more likely to have one or more contacts identified. Contacts screened at a different clinic to their index case or of male index cases were less likely to be evaluated than those screened at the same clinic or of women, respectively; yield of active disease was similar by sex. 10% (490/4850) of evaluated child contacts had latent TB infection. CONCLUSIONS: These are the first London-wide estimates of TB contact tracing indicators which are important for monitoring the strategy's success and informing risk assessment of index cases. Understanding why differences in indicators occur between groups could improve contact tracing outcomes

Kelvin-Helmholtz instabilities in Smoothed Particle Hydrodynamics

In this paper we investigate whether Smoothed Particle Hydrodynamics (SPH), equipped with artificial conductivity, is able to capture the physics of density/energy discontinuities in the case of the so-called shearing layers test, a test for examining Kelvin-Helmholtz (KH) instabilities. We can trace back each failure of SPH to show KH rolls to two causes: i) shock waves travelling in the simulation box and ii) particle clumping, or more generally, particle noise. The probable cause of shock waves is the Local Mixing Instability (LMI), previously identified in the literature. Particle noise on the other hand is a problem because it introduces a large error in the SPH momentum equation. We also investigate the role of artificial conductivity (AC). Including AC is necessary for the long-term behavior of the simulation (e.g. to get $\lambda=1/2, 1$ KH rolls). In sensitive hydrodynamical simulations great care is however needed in selecting the AC signal velocity, with the default formulation leading to too much energy diffusion. We present new signal velocities that lead to less diffusion. The effects of the shock waves and of particle disorder become less important as the time-scale of the physical problem (for the shearing layers problem: lower density contrast and higher Mach numbers) decreases. At the resolution of current galaxy formation simulations mixing is probably not important. However, mixing could become crucial for next-generation simulations.Comment: 16 pages, 23 figures, accepted for publication in MNRA

Should NICE reconsider the 2016 UK guidelines on TB contact tracing? A cost-effectiveness analysis of contact investigations in London.

BACKGROUND: In January 2016, clinical TB guidance in the UK changed to no longer recommend screening contacts of non-pulmonary, non-laryngeal (ETB) index cases. However, no new evidence was cited for this change, and there is evidence that screening these contacts may be worthwhile. The objective of this study was to estimate the cost-effectiveness of screening contacts of adult ETB cases and adult pulmonary or laryngeal TB (PTB) cases in London, UK. METHODS: We carried out a cross-sectional analysis of data collected on TB index cases and contacts in the London TB register and an economic evaluation using a static model describing contact tracing outcomes. Incremental cost-effectiveness ratios (ICERs) were calculated using no screening as the baseline comparator. All adult TB cases (≥15 years old) in London from 2012 to 2015, and their contacts, were eligible (2465/5084 PTB and 2559/6090 ETB index cases were included). RESULTS: Assuming each contact with PTB infects one person/month, the ICER of screening contacts of ETB cases was £78 000/quality-adjusted life-years (QALY) (95% CI 39 000 to 140 000), and screening contacts of PTB cases was £30 000/QALY (95% CI 18 000 to 50 000). The ICER of screening contacts of ETB cases was £30 000/QALY if each contact with PTB infects 3.4 people/month. Limitations of this study include the use of self-reported symptomatic periods and lack of knowledge about onward transmission from PTB contacts. CONCLUSIONS: Screening contacts of ETB cases in London was almost certainly not cost-effective at any conventional willingness-to-pay threshold in England, supporting recent changes to National Institute for Health and Care Excellence national guidelines

Pulmonary Mycobacterium avium-intracellulare is the main driver of the rise in non-tuberculous mycobacteria incidence in England, Wales and Northern Ireland, 2007–2012

BACKGROUND: The incidence of non-tuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW&NI) the reported rate of NTM more than doubled between 1996 and 2006. Although NTM infection has traditionally been associated with immunosuppressed individuals or those with severe underlying lung damage, pulmonary NTM infection and disease may occur in people with no overt immune deficiency. Here we report the incidence of NTM isolation in EW&NI between 2007 and 2012 from both pulmonary and extra-pulmonary samples obtained at a population level. METHODS: All individuals with culture positive NTM isolates between 2007 and 2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW&NI were included. RESULTS: Between 2007 and 2012, 21,118 individuals had NTM culture positive isolates. Over the study period the incidence rose from 5.6/100,000 in 2007 to 7.6/100,000 in 2012 (p < 0.001). Of those with a known specimen type, 90 % were pulmonary, in whom incidence increased from 4.0/100,000 to 6.1/100,000 (p < 0.001). In extra-pulmonary specimens this fell from 0.6/100,000 to 0.4/100,000 (p < 0.001). The most frequently cultured organisms from individuals with pulmonary isolates were within the M. avium-intracellulare complex family (MAC). The incidence of pulmonary MAC increased from 1.3/100,000 to 2.2/100,000 (p < 0.001). The majority of these individuals were over 60 years old. CONCLUSION: Using a population-based approach, we find that the incidence of NTM has continued to rise since the last national analysis. Overall, this represents an almost ten-fold increase since 1995. Pulmonary MAC in older individuals is responsible for the majority of this change. We are limited to reporting NTM isolates and not clinical disease caused by these organisms. To determine whether the burden of NTM disease is genuinely increasing, a standardised approach to the collection of linked national microbiological and clinical data is required