A review of congenital heart block

Congenital heart block is a rare disorder. It has an incidence of about 1 in 22,000 live births. It may be associated with high mortality and morbidity. This should generate a high index of suspicion for early diagnosis and aggressive therapy when appropriate. The congenital heart block associated with neonatal lupus is considered a form of passively acquired autoimmune disease in which maternal autoantibodies to the intracellular ribonucleoproteins Ro (SS-A) and La (SS-B), cross the placenta and injure the previously normal fetal heart. Women with serum titers of anti-Ro antibody carry a 3% risk of having a child with neonatal lupus syndrome. Recurrence rates are about 18%. We believe that serial echocardiograms should be acquired so that early diagnosis is made and aggressive therapy administered, if signs of conduction system disease such as PR interval prolongation by Doppler are found, so as to optimize the outcome. Establishment of guidelines for therapy have been set empirically, should signs of congenital heart block develop. Those patients whose congenital heart block is associated with structural heart disease have a higher morbidity and mortality, which is determined more by the underlying structural congenital heart disease than it is by the need for a pacemaker per se.peer-reviewe

Significant familial differences in the frequency of abortion and Toxoplasma gondii infection within a flock of Charollais sheep

A study was carried out to investigate the frequencies of abortion and congenital Toxoplasma gondii infection within 27 families (765 individuals) of a pedigree Charollais sheep flock maintained on a working farm in Worcestershire, UK, since 1992. Pedigree lambing records were analysed to establish the frequency of abortion for each family. The frequency of congenital infection was determined for each family by PCR analysis of tissue samples taken from newborn lambs. Atotal of 155 lambs were tested for congenital T. gondii infection, which were all born during the study period 2000–2003. Significant differences in the frequency of abortion between sheep families within this flock were observed with frequencies ranging between 0% and 48% (P<0.01). Significantly different infection frequencies with T. gondii were also observed for different families and ranged between 0% and 100% (P<0.01). Although the actual cause of each abortion was not verified, a highly significant positive correlation was found to exist between the frequency of abortion and the frequency of T. gondii infection in the same families (P<0.01). The data presented here raise further questions regarding the significance of congenital transmission of T. gondii within sheep populations, the possible successive vertical transmission of T. gondii within families of sheep, and the potential role of inherited genetic susceptibility to abortion with respect to T. gondii infection. This work invites further study into the epidemiology of ovine toxoplasmosis and may have implications for sheep husbandry methods in the future. Key words: Toxoplasma gondii, ovine, toxoplasmosis, congenital, transmission, pedigree, sheep

High levels of congenital transmission of toxoplasma gondii in longitudinal and cross-sectional studies on sheep farms provides evidence of vertical transmission in ovine hosts

Recent research suggests that vertical transmission may play an important role in sustaining Toxoplasma gondii infection in some species. We report here that congenital transmission occurs at consistently high levels in pedigree Charollais and outbred sheep flocks sampled over a 3-year period. Overall rates of transmission per pregnancy determined by PCR based diagnosis, were consistent over time in a commercial sheep flock (69%) and in sympatric (60%) and allopatric (41%) populations of Charollais sheep. The result of this was that 53·7% of lambs were acquiring an infection prior to birth: 46·4% of live lambs and 90·0% of dead lambs (in agreement with the association made between T. gondii and abortion). No significant differences were observed between lamb sexes. Although we cannot distinguish between congenital transmission occurring due to primary infection at pregnancy or reactivation of chronic infection during pregnancy, our observations of consistently high levels of congenital transmission over successive lambings favour the latter

Statistical properties of hybrid estimators proposed for GEDI – NASA’s Global Ecosystem Dynamics Investigation

NASA’s Global Ecosystem Dynamics Investigation (GEDI) mission will collect waveform lidar data at a dense sample of ∼25 m footprints along ground tracks paralleling the orbit of the International Space Station (ISS). GEDI’s primary science deliverable will be a 1 km grid of estimated mean aboveground biomass density (Mg ha ^−1 ), covering the latitudes overflown by ISS (51.6 °S to 51.6 °N). One option for using the sample of waveforms contained within an individual grid cell to produce an estimate for that cell is hybrid inference, which explicitly incorporates both sampling design and model parameter covariance into estimates of variance around the population mean. We explored statistical properties of hybrid estimators applied in the context of GEDI, using simulations calibrated with lidar and field data from six diverse sites across the United States. We found hybrid estimators of mean biomass to be unbiased and the corresponding estimators of variance appeared to be asymptotically unbiased, with under-estimation of variance by approximately 20% when data from only two clusters (footprint tracks) were available. In our study areas, sampling error contributed more to overall estimates of variance than variability due to the model, and it was the design-based component of the variance that was the source of the variance estimator bias at small sample sizes. These results highlight the importance of maximizing GEDI’s sample size in making precise biomass estimates. Given a set of assumptions discussed here, hybrid inference provides a viable framework for estimating biomass at the scale of a 1 km grid cell while formally accounting for both variability due to the model and sampling error

Microencapsulated islet allografts in diabetic NOD mice and nonhuman primates

OBJECTIVE: Our goal was to assess the efficacy of encapsulated allogeneic islets transplanted in diabetic NOD mice and streptozotocin (STZ)-diabetic nonhuman primates (NHPs).MATERIALS AND METHODS: Murine or NHP islets were microencapsulated and transplanted in non-immunosuppressed mice or NHPs given clinically-acceptable immunosuppressive regimens, respectively. Two NHPs were treated with autologous mesenchymal stem cells (MSCs) and peri-transplant oxygen therapy. Different transplant sites (intraperitoneal [i.p.], omental pouch, omental surface, and bursa omentalis) were tested in separate NHPs. Graft function was monitored by exogenous insulin requirements, fasting blood glucose levels, glucose tolerance tests, percent hemoglobin A1c (% HbA1c), and C-peptide levels. In vitro assessment of grafts included histology, immunohistochemistry, and viability staining; host immune responses were characterized by flow cytometry and cytokine/chemokine multiplex ELISAS.RESULTS: Microencapsulated islet allografts functioned long-term i.p. in diabetic NOD mice without immunosuppression, but for a relatively short time in immunosuppressed NHPs. In the NHPs, encapsulated allo-islets initially reduced hyperglycemia, decreased exogenous insulin requirements, elevated C-peptide levels, and lowered % HbA1c in plasma, but graft function diminished with time, regardless of transplant site. At necropsy, microcapsules were intact and non-fibrotic, but many islets exhibited volume loss, central necrosis and endogenous markers of hypoxia. Animals receiving supplemental oxygen and autologous MSCs showed improved graft function for a longer post-transplant period. In diabetic NHPs and mice, cell-free microcapsules did not elicit a fibrotic response.CONCLUSIONS: The evidence suggested that hypoxia was a major factor for damage to encapsulated islets in vivo. To achieve long-term function, new approaches must be developed to increase the oxygen supply to microencapsulated islets and/or identify donor insulin-secreting cells which can tolerate hypoxia.</p

GEDI launches a new era of biomass inference from space

Accurate estimation of aboveground forest biomass stocks is required to assess the impacts of land use changes such as deforestation and subsequent regrowth on concentrations of atmospheric CO2. The Global Ecosystem Dynamics Investigation (GEDI) is a lidar mission launched by NASA to the International Space Station in 2018. GEDI was specifically designed to retrieve vegetation structure within a novel, theoretical sampling design that explicitly quantifies biomass and its uncertainty across a variety of spatial scales. In this paper we provide the estimates of pan-tropical and temperate biomass derived from two years of GEDI observations. We present estimates of mean biomass densities at 1 km resolution, as well as estimates aggregated to the national level for every country GEDI observes, and at the sub-national level for the United States. For all estimates we provide the standard error of the mean biomass. These data serve as a baseline for current biomass stocks and their future changes, and the mission's integrated use of formal statistical inference points the way towards the possibility of a new generation of powerful monitoring tools from space

Update of the best practice dietetic management of overweight and obese children and adolescents: a systematic review protocol

To update an existing systematic review series of randomized controlled trials (RCT) that include a dietary intervention for the management of overweight or obesity in children or adolescents.Specifically, the review questions are: In randomized controlled trials of interventions which include a dietary intervention for the management of overweight or obesity in children or adolescents

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes