A combined DTI-fMRI approach for optimizing the delineation of posteromedial vs. anterolateral entorhinal cortex

In the entorhinal cortex (EC), attempts have been made to identify the human homologue regions of the medial (MEC) and lateral (LEC) subdivision using either functional magnetic resonance imaging (fMRI) or diffusion tensor imaging (DTI). However, there are still discrepancies between entorhinal subdivisions depending on the choice of connectivity seed regions and the imaging modality used. While DTI can be used to follow the white matter tracts of the brain, fMRI can identify functionally connected brain regions. In this study, we used both DTI and resting-state fMRI in 103 healthy adults to investigate both structural and functional connectivity between the EC and associated cortical brain regions. Differential connectivity with these regions was then used to predict the locations of the human homologues of MEC and LEC. Our results from combining DTI and fMRI support a subdivision into posteromedial (pmEC) and anterolateral (alEC) EC and reveal a discrete border between the pmEC and alEC. Furthermore, the EC subregions obtained by either imaging modality showed similar distinct connectivity patterns: While pmEC showed increased connectivity preferentially with the default mode network, the alEC exhibited increased connectivity with regions in the dorsal attention and salience networks. Optimizing the delineation of the human homologues of MEC and LEC with a combined, cross-validated DTI-fMRI approach allows to define a likely border between the two subdivisions and has implications for both cognitive and translational neuroscience research

Structural connectivity-based segmentation of the human entorhinal cortex

The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posteromedial (pmEC) and anterolateral (alEC) parts, but uncertainty remains about the choice of imaging modality and seed regions, in particular in light of a substantial revision of the classical model of EC connectivity based on novel insights from rodent anatomy. Here, we used structural, not functional imaging, namely diffusion tensor imaging (DTI) and probabilistic tractography to segment the human EC based on differential connectivity to other brain regions known to project selectively to MEC or LEC. We defined MEC as more strongly connected with presubiculum and retrosplenial cortex (RSC), and LEC as more strongly connected with distal CA1 and proximal subiculum (dCA1pSub) and lateral orbitofrontal cortex (OFC). Although our DTI segmentation had a larger medial-lateral component than in the previous fMRI studies, our results show that the human MEC and LEC homologues have a border oriented both towards the posterior-anterior and medial-lateral axes, supporting the differentiation between pmEC and alEC

Occlusion and Temporomandibular Function among Subjects with Mandibular Distal Extension Removable Partial Dentures

Objective. To quantify effects on occlusion and temporomandibular function of mandibular distal extension removable partial dentures in shortened dental arches. Methods. Subjects wearing mandibular extension removable partial dentures (n = 25) were compared with subjects with shortened dental arches without extension (n = 74) and with subjects who had worn a mandibular extension removable partial denture in the past (n = 19). Subjects with complete dentitions (n = 72) were controls. Data were collected at baseline and at 3-, 6-, and 9-year observations. Results. Occlusal activity in terms of reported awareness of bruxism and occlusal tooth wear of lower anterior teeth did not differ significantly between the groups. In contrast, occlusal tooth wear of premolars in shortened dental arches with or without extension dentures was significantly higher than in the controls. Differences amongst groups with respect to signs and symptoms related to temporomandibular disorders were not found. Occlusal support of the dentures did not influence anterior spatial relationship. Occlusal contacts of the denture teeth decreased from 70% for second premolars via 50% for first molars, to 30% for second molars. Conclusions. Mandibular distal extension removable partial dentures in moderate shortened dental arches had no effects on occlusion and temporomandibular function

Toward Near‐Field Tsunami Forecasting Along the Cascadia Subduction Zone Using Rapid GNSS Source Models

Over the past 15 years and through multiple large and devastating earthquakes, tsunami warning systems have grown considerably in their efficacy in providing timely and accurate forecasts to affected communities. However, one part of tsunami warning that still needs improvement is forecasts catered to local, near‐field communities in the time after an earthquake rupture but before coastal inundation. In this study, we test a rapid, Global Navigation Satellite Systems (GNSS)‐driven earthquake characterization model using a large data set of synthetic megathrust ruptures for its near‐field tsunami forecasting potential. We also provide a framework for tsunami forecasting that focuses on the likelihood of exceedance of user‐defined coastal amplitudes that may be of use in the first 15 min following an earthquake. Specifically, we can estimate the earthquake magnitude, without saturation, for 82% of tested ruptures. We can also identify test ruptures as dominantly thrust events, without analyst guidance for 92% of tested thrust ruptures. Finally, modeling the tsunami component of our rapidly estimated fault rupture leads to greater than 80% accuracy in identifying tsunami impact at key coastal amplitude thresholds. This is promising for near‐field warning when the time prior to inundation is limited to tens of minutes. We focus this study on large megathrust ruptures along the quiescent Cascadia subduction zone where there is already a dense GNSS network

Incorporating comorbidity within risk adjustment for UK pediatric cardiac surgery

INTRODUCTION: When considering early survival rates after pediatric cardiac surgery it is essential to adjust for risk linked to case complexity. An important but previously less well understood component of case mix complexity is comorbidity. METHODS: National congenital heart diseases audit (NCHDA) data representing all pediatric cardiac surgery procedures undertaken in the United Kingdom and Ireland between 2009 and 2014 was used to develop and test groupings for comorbidity and additional non procedure based risk factors within a risk adjustment model for 30-day mortality. A mixture of expert consensus based opinion and empiric statistical analyses were used to define and test the new comorbidity groups. RESULTS: The study dataset consisted of 21,838 pediatric cardiac surgical procedure episodes in 18,834 patients with 539 deaths (raw 30-day mortality rate 2.5%). In addition to surgical procedure type, primary cardiac diagnosis, univentricular status, age, weight, procedure type (bypass, non-bypass or hybrid) and era, the new risk factor groups of: non Downs congenital anomalies, acquired comorbidities, increased severity of illness indicators (such as pre-operative mechanical ventilation or circulatory support) and additional cardiac risk factors (such as heart muscle conditions and raised pulmonary arterial pressure) all independently increased the risk of operative mortality. DISCUSSION: In an era of low mortality rates across a wide range of operations, non-procedure based risk factors form a vital element of risk adjustment and their presence leads to wide variations in the predicted risk of a given operation

Improving Risk Adjustment for Mortality After Pediatric Cardiac Surgery: The UK PRAiS2 Model

BACKGROUND: Partial Risk Adjustment in Surgery (PRAiS), a risk model for 30-day mortality after children's heart surgery, has been used by the UK National Congenital Heart Disease Audit to report expected risk-adjusted survival since 2013. This study aimed to improve the model by incorporating additional comorbidity and diagnostic information. METHODS: The model development dataset was all procedures performed between 2009 and 2014 in all UK and Ireland congenital cardiac centers. The outcome measure was death within each 30-day surgical episode. Model development followed an iterative process of clinical discussion and development and assessment of models using logistic regression under 25 × 5 cross-validation. Performance was measured using Akaike information criterion, the area under the receiver-operating characteristic curve (AUC), and calibration. The final model was assessed in an external 2014 to 2015 validation dataset. RESULTS: The development dataset comprised 21,838 30-day surgical episodes, with 539 deaths (mortality, 2.5%). The validation dataset comprised 4,207 episodes, with 97 deaths (mortality, 2.3%). The updated risk model included 15 procedural, 11 diagnostic, and 4 comorbidity groupings, and nonlinear functions of age and weight. Performance under cross-validation was: median AUC of 0.83 (range, 0.82 to 0.83), median calibration slope and intercept of 0.92 (range, 0.64 to 1.25) and -0.23 (range, -1.08 to 0.85) respectively. In the validation dataset, the AUC was 0.86 (95% confidence interval [CI], 0.82 to 0.89), and the calibration slope and intercept were 1.01 (95% CI, 0.83 to 1.18) and 0.11 (95% CI, -0.45 to 0.67), respectively, showing excellent performance. CONCLUSIONS: A more sophisticated PRAiS2 risk model for UK use was developed with additional comorbidity and diagnostic information, alongside age and weight as nonlinear variables

Validation of the Brief Developmental Assessment in pre-school children with heart disease

INTRODUCTION: The objective of this study was to prospectively validate the “Brief Developmental Assessment”, which is a new early recognition tool for neurodevelopmental abnormalities in children with heart disease that was developed for use by cardiac teams. METHODS: This was a prospective validation study among a representative sample of 960 pre-school children with heart disease from three United Kingdom tertiary cardiac centres who were analysed grouped into five separate age bands. RESULTS: The “Brief Developmental Assessment” was successfully validated in the older four age bands, but not in the youngest representing infants under the age of 4 months, as pre-set validation thresholds were met – lower 95% confidence limit for the correlation coefficient above 0.75 – in terms of agreement of scores between two raters and with an external measure the “Mullen Scales of Early Learning”. On the basis of American Association of Pediatrics Guidelines, which state that the sensitivity and specificity of a developmental screening tool should fall between 70 and 80%, “Brief Developmental Assessment” outcome of Red meets this threshold for detection of Mullen scores >2 standard deviations below the mean. CONCLUSION: The “Brief Developmental Assessment” may be used to improve the quality of assessment of children with heart disease. This will require a training package for users and a guide to action for abnormal results. Further research is needed to determine how best to deploy the “Brief Developmental Assessment” at different time points in children with heart disease and to determine the management strategy in infants younger than 4 months old

More on Supersymmetric Domain Walls, N Counting and Glued Potentials

Various features of domain walls in supersymmetric gluodynamics are discussed. We give a simple field-theoretic interpretation of the phenomenon of strings ending on the walls recently conjectured by Witten. An explanation of this phenomenon in the framework of gauge field theory is outlined. The phenomenon is argued to be particularly natural in supersymmetric theories which support degenerate vacuum states with distinct physical properties. The issue of existence (or non-existence) of the BPS saturated walls in the theories with glued (super)potentials is addressed. The amended Veneziano-Yankielowicz effective Lagrangian belongs to this class. The physical origin of the cusp structure of the effective Lagrangian is revealed, and the limitation it imposes on the calculability of the wall tension is explained. Related problems are considered. In particular, it is shown that the so called discrete anomaly matching, when properly implemented, does not rule out the chirally symmetric phase of supersymmetric gluodynamics, contrary to recent claims.Comment: 40 pages, Latex, 5 figures. Several references added, final version to be published in Physical Review

A process evaluation of user fees abolition for pregnant women and children under five years in two districts in Niger (West Africa)

<p>Abstract</p> <p>Background</p> <p>African policy-makers are increasingly considering abolishing user fees as a solution to improve access to health care systems. There is little evidence on this subject in West Africa, and particularly in countries that have organized their healthcare system on the basis of the Bamako Initiative. This article presents a process evaluation of an NGO intervention to abolish user fees in Niger for children under five years and pregnant women.</p> <p>Methods</p> <p>The intervention was launched in 2006 in two health districts and 43 health centres. The intervention consisted of abolishing user fees and improving the quality of services (drugs, ambulance, etc.). We carried out a process evaluation in April 2007 using qualitative and quantitative data. Three data collection methods were used: i) individual in-depth interviews (n = 85) and focus groups (n = 8); ii) participant observation in 12 health centres; and iii) self-administered structured questionnaires (n = 51 health staff).</p> <p>Results</p> <p>The population favoured abolition; health officials and local decision-makers were in favour, but they worried about its sustainability. Among health workers, opposition to providing free services was more widespread. The strengths of the process were: a top-down phase of information and raising community awareness; appropriate incentive measures; a good drug supply system; and the organization of a medical evacuation system. The major weaknesses of the process were: the perverse effects of incentive bonuses; the lack of community-based management committees' involvement in the management; the creation of a system running in parallel with the BI system; the lack of action to support the service offer; and the poor coordination of the availability of free services at different levels of the health pyramid. Some unintended outcomes are also documented.</p> <p>Conclusion</p> <p>The linkages between systems in which some patients pay (Bamako Initiative) and some do not should be carefully considered and organized in accordance with the local reality. For the poorest patients to really benefit, it is essential that, at the same time, the quality of services be improved and mechanisms be put in place to prevent abuses. Much remains to be done to generate knowledge on the processes for abolishing fees in West Africa.</p

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events