Childhood Bradycardia Associates With Atrioventricular Conduction Defects in Older Age: A Longitudinal Birth Cohort Study

Background: This study explored the association between childhood bradycardia and later‐life cardiac phenotype using longitudinal data from the 1946 National Survey of Health and Development (NSHD) birth cohort. // Methods and Results: Resting heart rate was recorded at 6 and 7 years of age to provide the bradycardia exposure defined as a childhood resting heart rate <75 bpm. Three outcomes were studied: (1) echocardiographic data at 60 to 64 years of age, consisting of ejection fraction, left ventricular mass index, myocardial contraction fraction index, and E/e′; (2) electrocardiographic evidence of atrioventricular or ventricular conduction defects by 60 to 64 years of age; and (3) all‐cause and cardiovascular mortality. Generalized linear models or Cox regression models were used, and adjustment was made for relevant demographic and health‐related covariates, and for multiple testing. Mixed generalized linear models and fractional polynomials were used as sensitivity analyses. One in 3 older adults with atrioventricular conduction defects had been bradycardic in childhood, with defects being serious (Mobitz type II second‐degree atrioventricular block or higher) in 12%. In fully adjusted models, childhood bradycardia was associated with 2.91 higher odds of atrioventricular conduction defects (95% CI, 1.59–5.31; P=0.0005). Associations persisted in random coefficients mixed generalized linear models (odds ratio, 2.50; 95% CI, 1.01–4.31). Fractional polynomials confirmed a linear association between the log odds of atrioventricular conduction defects at 60 to 64 years of age and resting heart rate at 7 years of age. There was no association between bradycardia in childhood and mortality outcomes or with echocardiographic parameters and ventricular conduction defects in older age. // Conclusions: Longitudinal birth cohort data indicate that childhood bradycardia trebles the odds of having atrioventricular conduction defects in older age, 88% of which are benign. In addition, it does not influence mortality or heart size and function. Future research should concentrate on identifying children at risk

Strongholds of Ostrea edulis populations in estuaries in Essex, SE England and their association with traditional oyster aquaculture: evidence to support a MPA designation

The flat oyster Ostrea edulis has declined significantly in European waters since the 1850s as a result of anthropogenic activity. Ostrea edulis was designated a UK Biodiversity Action Plan Species and Habitat in 1995, and as a Feature of Conservation Importance (FOCI) within the UK Marine & Coastal Access Act 2009. To promote the recovery of oyster beds, a greater understanding of its abundance and distribution is required. Distribution of O. edulis across the proposed Blackwater, Crouch, Roach and Colne MCZ in Essex was determined between 2008 and 2012. Ostrea edulis were present in four estuary zones; with highest sample abundance in the Blackwater and Ray Sand zones. Size structure of populations varied, with the Ray Sand and Colne zones showing a significant lack of individuals with shell height <39 mm. Ostrea edulis occurred in highest number on shell substratum, followed by silty sediments. There were no significant associations between O. edulis abundance or size structure with water column Chl a, suspended solids, oxygen, nitrate or ammonium concentrations, temperature or pH. Highest abundance and most equitable population shell-size distribution for O. edulis were located within, or adjacent to, actively managed aquaculture zones. This suggests that traditional seabed management contributed to the maintenance or recovery of the species of conservation concern. Demonstration that the Essex estuaries were a stronghold for Ostrea edulis in the southern North sea area led to the designation of the Blackwater, Crouch, Roach and Colne estuaries Marine Conservation Zone in 2013

Longitudinal birth cohort study finds that life-course frailty associates with later-life heart size and function.

A frailty index (FI) counts health deficit accumulation. Besides traditional risk factors, it is unknown whether the health deficit burden is related to the appearance of cardiovascular disease. In order to answer this question, the same multidimensional FI looking at 45-health deficits was serially calculated per participant at 4 time periods (0-16, 19-44, 45-54 and 60-64 years) using data from the 1946 Medical Research Council (MRC) British National Survey of Health and Development (NSHD)-the world's longest running longitudinal birth cohort with continuous follow-up. From these the mean and total FI for the life-course, and the step change in deficit accumulation from one time period to another was derived. Echocardiographic data at 60-64 years provided: ejection fraction (EF), left ventricular mass indexed to body surface area (LVmassi, BSA), myocardial contraction fraction indexed to BSA (MCFi) and E/e'. Generalized linear models assessed the association between FIs and echocardiographic parameters after adjustment for relevant covariates. 1375 participants were included. For each single new deficit accumulated at any one of the 4 time periods, LVmassi increased by 0.91-1.44% (p < 0.013), while MCFi decreased by 0.6-1.02% (p < 0.05). A unit increase in FI at age 45-54 and 60-64, decreased EF by 11-12% (p < 0.013). A single health deficit step change occurring between 60 and 64 years and one of the earlier time periods, translated into higher odds (2.1-78.5, p < 0.020) of elevated LV filling pressure. Thus, the accumulation of health deficits at any time period of the life-course associates with a maladaptive cardiac phenotype in older age, dominated by myocardial hypertrophy and poorer function

Primary Progressive Aphasia: Toward a Pathophysiological Synthesis

PURPOSE OF REVIEW: The term primary progressive aphasia (PPA) refers to a diverse group of dementias that present with prominent and early problems with speech and language. They present considerable challenges to clinicians and researchers. RECENT FINDINGS: Here, we review critical issues around diagnosis of the three major PPA variants (semantic variant PPA, nonfluent/agrammatic variant PPA, logopenic variant PPA), as well as considering 'fragmentary' syndromes. We next consider issues around assessing disease stage, before discussing physiological phenotyping of proteinopathies across the PPA spectrum. We also review evidence for core central auditory impairments in PPA, outline critical challenges associated with treatment, discuss pathophysiological features of each major PPA variant, and conclude with thoughts on key challenges that remain to be addressed. New findings elucidating the pathophysiology of PPA represent a major step forward in our understanding of these diseases, with implications for diagnosis, care, management, and therapies

A Genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology

We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and "TAU" transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation. All data are available and searchable at http://www.mouseac.org

REDD+ on the rocks? Conflict over forest and politics of justice in Vietnam

In Vietnam, villagers involved in a REDD+ (reduced emissions from deforestation and forest degradation) pilot protect areas with rocks which have barely a tree on them. The apparent paradox indicates how actual practices differ from general ideas about REDD+ due to ongoing conflict over forest, and how contestations over the meaning of justice are a core element in negotiations over REDD+. We explore these politics of justice by examining how the actors involved in the REDD+ pilot negotiate the particular subjects, dimensions, and authority of justice considered relevant, and show how politics of justice are implicit to practical decisions in project implementation. Contestations over the meaning of justice are an important element in the practices and processes constituting REDD+ at global, national and local levels, challenging uniform definitions of forest justice and how forests ought to be managed

Relative blocking in posets

Poset-theoretic generalizations of set-theoretic committee constructions are presented. The structure of the corresponding subposets is described. Sequences of irreducible fractions associated to the principal order ideals of finite bounded posets are considered and those related to the Boolean lattices are explored; it is shown that such sequences inherit all the familiar properties of the Farey sequences.Comment: 29 pages. Corrected version of original publication which is available at http://www.springerlink.com, see Corrigendu

TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis

Background: TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS.Methodology/Principal Findings: To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus.Conclusions: Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American

Relationship between temporomandibular joint dynamics and mouthguards: feasibility of a test method

A test system was developed establishing the feasibility of collecting biomechanical data as they relate to the use of mouthguards. Previous experimental studies have examined the physical and mechanical properties of mouthguard materials. This information has been used as a guide for establishing material standards and specifications for the fabrication of mouthguards, but it lacks the key biomechanical parameters required for a thorough mouthguard evaluation. The current study was designed to assess whether the impact force, condylar deflection, and strain superior to the temporomandibular joint region could be measured. A drop test was conducted on a cadaveric specimen to simulate loading at the chin point. To measure the force of impact, an accelerometer was attached to an impactor of known mass. High-speed biplanar (1000 frames per second) radiographs were used to determine condylar displacement. Radio-opaque markers were inserted into the bone at predetermined locations. Total displacement of these markers was determined in reference to anatomical landmarks. Strain gauges were attached to the mandible and skull to monitor the effects of the condyle impacting the base of the skull. Based on the data collected, forces were calculated by determining the product of the time-based acceleration and known mass. A measurable change in force between the mouthguards and the control (no mouthguard) was demonstrated. The average condylar displacement was successfully measured and indicated as an increase in total deflection for impacts conducted with mouthguards. Quantifiable strain was measured in the region above the mandibular fossa with and without the insertion of a mouthguard at all impact conditions. However, it was determined that additional gauges would provide critical data. Key biomechanical parameters for chin-point impacts were determined in the current study. The technique demonstrated that both displacement within the mandibular fossa and loading of the condyles occur during the impact event. Although the current study established a technique that can be used to examine the relationship between mouthguards and jaw-joint injuries, the role, if any, mouthguards play in the reduction of injuries cannot be established until a thorough analysis is completed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74031/1/j.1600-9657.2004.00213.x.pd

Positional Information – a concept underpinning our understanding of developmental biology

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