MRI based preterm white matter injury classification: the importance of sequential imaging in determining severity of injury

The evolution of non-hemorrhagic white matter injury (WMI) based on sequential magnetic resonance imaging (MRI) has not been well studied. Our aim was to describe sequential MRI findings in preterm infants with non-hemorrhagic WMI and to develop an MRI classification system for preterm WMI based on these findings.Eighty-two preterm infants (gestation ≤35 weeks) were retrospectively included. WMI was diagnosed and classified based on sequential cranial ultrasound (cUS) and confirmed on MRI.138 MRIs were obtained at three time-points: early (<2 weeks; n = 32), mid (2-6 weeks; n = 30) and term equivalent age (TEA; n = 76). 63 infants (77%) had 2 MRIs during the neonatal period. WMI was non-cystic in 35 and cystic in 47 infants. In infants with cystic-WMI early MRI showed extensive restricted diffusion abnormalities, cysts were already present in 3 infants; mid MRI showed focal or extensive cysts, without acute diffusion changes. A significant reduction in the size and/or extent of the cysts was observed in 32% of the infants between early/mid and TEA MRI. In 4/9 infants previously seen focal cysts were no longer identified at TEA. All infants with cystic WMI showed ≥2 additional findings at TEA: significant reduction in WM volume, mild-moderate irregular ventriculomegaly, several areas of increased signal intensity on T1-weighted-images, abnormal myelination of the PLIC, small thalami.In infants with extensive WM cysts at 2-6 weeks, cysts may be reduced in number or may even no longer be seen at TEA. A single MRI at TEA, without taking sequential cUS data and pre-TEA MRI findings into account, may underestimate the extent of WMI; based on these results we propose a new MRI classification for preterm non-hemorrhagic WMI

Role of EEG background activity, seizure burden and MRI in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischaemic encephalopathy in the era of therapeutic hypothermia

OBJECTIVE: To investigate the role of EEG background activity, electrographic seizure burden, and MRI in predicting neurodevelopmental outcome in infants with hypoxic-ischaemic encephalopathy (HIE) in the era of therapeutic hypothermia. METHODS: Twenty-six full-term infants with HIE (September 2011-September 2012), who had video-EEG monitoring during the first 72 h, an MRI performed within the first two weeks and neurodevelopmental assessment at two years were evaluated. EEG background activity at age 24, 36 and 48 h, seizure burden, and severity of brain injury on MRI, were compared and related to neurodevelopmental outcome. RESULTS: EEG background activity was significantly associated with neurodevelopmental outcome at 36 h (p = 0.009) and 48 h after birth (p = 0.029) and with severity of brain injury on MRI at 36 h (p = 0.002) and 48 h (p = 0.018). All infants with a high seizure burden and moderate-severe injury on MRI had an abnormal outcome. The positive predictive value (PPV) of EEG for abnormal outcome was 100% at 36 h and 48 h and the negative predictive value (NPV) was 75% at 36 h and 69% at 48 h. The PPV of MRI was 100% and the NPV 85%. The PPV of seizure burden was 78% and the NPV 71%. CONCLUSION: Severely abnormal EEG background activity at 36 h and 48 h after birth was associated with severe injury on MRI and abnormal neurodevelopmental outcome. High seizure burden was only associated with abnormal outcome in combination with moderate-severe injury on MRI

A Geographically-Restricted but Prevalent Mycobacterium tuberculosis Strain Identified in the West Midlands Region of the UK between 1995 and 2008

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, p 65 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

The what and where of adding channel noise to the Hodgkin-Huxley equations

One of the most celebrated successes in computational biology is the Hodgkin-Huxley framework for modeling electrically active cells. This framework, expressed through a set of differential equations, synthesizes the impact of ionic currents on a cell's voltage -- and the highly nonlinear impact of that voltage back on the currents themselves -- into the rapid push and pull of the action potential. Latter studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional) description than the original Hodgkin-Huxley equations. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic Hodgkin-Huxley equations. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly Matlab simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950) and http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl

A falls prevention programme to improve quality of life, physical function and falls efficacy in older people receiving home help services: study protocol for a randomised controlled trial

BACKGROUND: Falls and fall-related injuries in older adults are associated with great burdens, both for the individuals, the health care system and the society. Previous research has shown evidence for the efficiency of exercise as falls prevention. An understudied group are older adults receiving home help services, and the effect of a falls prevention programme on health-related quality of life is unclear. The primary aim of this randomised controlled trial is to examine the effect of a falls prevention programme on quality of life, physical function and falls efficacy in older adults receiving home help services. A secondary aim is to explore the mediating factors between falls prevention and health-related quality of life. METHODS: The study is a single-blinded randomised controlled trial. Participants are older adults, aged 67 or older, receiving home help services, who are able to walk with or without walking aids, who have experienced at least one fall during the last 12 months and who have a Mini Mental State Examination of 23 or above. The intervention group receives a programme, based on the Otago Exercise Programme, lasting 12 weeks including home visits and motivational telephone calls. The control group receives usual care. The primary outcome is health-related quality of life (SF-36). Secondary outcomes are leg strength, balance, walking speed, walking habits, activities of daily living, nutritional status and falls efficacy. All measurements are performed at baseline, following intervention at 3 months and at 6 months' follow-up. Sample size, based on the primary outcome, is set to 150 participants randomised into the two arms, including an estimated 15-20% drop out. Participants are recruited from six municipalities in Norway. DISCUSSION: This trial will generate new knowledge on the effects of an exercise falls prevention programme among older fallers receiving home help services. This knowledge will be useful for clinicians, for health managers in the primary health care service and for policy makers

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Early cranial ultrasound findings among infants with neonatal encephalopathy in Uganda: an observational study.

BACKGROUND: In sub-Saharan Africa, the timing and nature of brain injury and their relation to mortality in neonatal encephalopathy (NE) are unknown. We evaluated cranial ultrasound (cUS) scans from term Ugandan infants with and without NE for evidence of brain injury. METHODS: Infants were recruited from a national referral hospital in Kampala. Cases (184) had NE and controls (100) were systematically selected unaffected term infants. All had cUS scans <36 h reported blind to NE status. RESULTS: Scans were performed at median age 11.5 (interquartile range (IQR): 5.2-20.2) and 8.4 (IQR: 3.6-13.5) hours, in cases and controls respectively. None had established antepartum injury. Major evolving injury was reported in 21.2% of the cases vs. 1.0% controls (P < 0.001). White matter injury was not significantly associated with bacteremia in encephalopathic infants (odds ratios (OR): 3.06 (95% confidence interval (CI): 0.98-9.60). Major cUS abnormality significantly increased the risk of neonatal death (case fatality 53.9% with brain injury vs. 25.9% without; OR: 3.34 (95% CI: 1.61-6.95)). CONCLUSION: In this low-resource setting, there was no evidence of established antepartum insult, but a high proportion of encephalopathic infants had evidence of major recent and evolving brain injury on early cUS imaging, suggesting prolonged or severe acute exposure to hypoxia-ischemia (HI). Early abnormalities were a significant predictor of death

Gaze following in an asocial reptile (Eublepharis macularius)

Gaze following is the ability to utilise information from another's gaze. It is most often seen in a social context or as a reflexive response to interesting external stimuli. Social species can potentially reveal utilisable knowledge about another's future intentions by attending to the target of their gaze. However, in even more fundamental situations, being sensitive to another's gaze can also be useful such as when it can facilitate greater foraging efficiency or lead to earlier predator detection. While gaze sensitivity has been shown to be prevalent in a number of social species, little is currently known about the potential for gaze following in asocial species. The current study investigated whether an asocial reptile, the leopard gecko (Eublepharis macularius), could reliably use the visual indicators of attention to follow the gaze of a conspecific around a barrier. We operated three trial conditions and found subjects (N = 6) responded significantly more to the conspecific demonstrator looking up at a laser stimulus projected onto an occluder during the experimental condition compared to either of two control conditions. The study's findings point toward growing evidence for gaze-following ability in reptiles, who are typically categorised as asocial. Furthermore, our findings support developing comparative social cognition research showing the origins of gaze following and other cognitive behaviours that may be more widely distributed across taxonomic groups than hitherto thought

Environmental influences on energy balance-related behaviors: A dual-process view

BACKGROUND: Studies on the impact of the 'obesogenic' environment have often used non-theoretical approaches. In this journal's debate and in other papers authors have argued the necessity of formulating conceptual models for differentiating the causal role of environmental influences on behavior. DISCUSSION: The present paper aims to contribute to the debate by presenting a dual-process view on the environment – behavior relationship. This view is conceptualized in the EnRG framework (Environmental Research framework for weight Gain prevention). In the framework, behavior is postulated to be the result of a simultaneous influence of conscious and unconscious processes. Environmental influences are hypothesized to influence behavior both indirectly and directly. The indirect causal mechanism reflects the mediating role of behavior-specific cognitions in the influence of the environment on behavior. A direct influence reflects the automatic, unconscious, influence of the environment on behavior. Specific personal and behavioral factors are postulated to moderate the causal path (i.e., inducing either the automatic or the cognitively mediated environment – behavior relation). In addition, the EnRG framework applies an energy balance-approach, stimulating the integrated study of determinants of diet and physical activity. CONCLUSION: The application of a dual-process view may guide research towards causal mechanisms linking specific environmental features with energy balance-related behaviors in distinct populations. The present paper is hoped to contribute to the evolution of a paradigm that may help to disentangle the role of 'obesogenic' environmental factors