Risk-based strategies for surveillance of tuberculosis infection in cattle for low-risk areas in England and Scotland.

Disease surveillance can be made more effective by either improving disease detection, providing cost savings, or doing both. Currently, cattle herds in low-risk areas (LRAs) for bovine tuberculosis (bTB) in England are tested once every 4 years. In Scotland, the default herd testing frequency is also 4 years, but a risk-based system exempts some herds from testing altogether. To extend this approach to other areas, a bespoke understanding of at-risk herds and how risk-based surveillance can affect bTB detection is required. Here, we use a generalized linear mixed model to inform a Bayesian probabilistic model of freedom from infection and explore risk-based surveillance strategies in LRAs and Scotland. Our analyses show that in both areas the primary herd-level risk factors for bTB infection are the size of the herd and purchasing cattle from high-risk areas of Great Britain and/or Ireland. A risk-based approach can improve the current surveillance system by both increasing detection (9% and 7% fewer latent infections), and reducing testing burden (6% and 26% fewer animal tests) in LRAs and Scotland, respectively. Testing at-risk herds more frequently can also improve the level of detection by identifying more infected cases and reducing the hidden burden of the disease, and reduce surveillance effort by exempting low-risk herds from testing.

Importance of mitochondrial haplotypes and maternal lineage in sprint performance among individuals of West African ancestry.

Mitochondrial DNA (mtDNA) is inherited solely along the matriline, giving insight into both ancestry and prehistory. Individuals of sub-Saharan ancestry are overrepresented in sprint athletics, suggesting a genetic advantage. The purpose of this study was to compare the mtDNA haplogroup data of elite groups of Jamaican and African-American sprinters against respective controls to assess any differences in maternal lineage. The first hypervariable region of mtDNA was haplogrouped in elite Jamaican athletes (N=107) and Jamaican controls (N=293), and elite African-American athletes (N=119) and African-American controls (N=1148). Exact tests of total population differentiation were performed on total haplogroup frequencies. The frequency of non-sub-Saharan haplogroups in Jamaican athletes and Jamaican controls was similar (1.87% and 1.71%, respectively) and lower than that of African-American athletes and African-American controls (21.01% and 8.19%, respectively). There was no significant difference in total haplogroup frequencies between Jamaican athletes and Jamaican controls (P=0.551 ± 0.005); however, there was a highly significant difference between African-American athletes and African-American controls (P<0.001). The finding of statistically similar mtDNA haplogroup distributions in Jamaican athletes and Jamaican controls suggests that elite Jamaican sprinters are derived from the same source population and there is neither population stratification nor isolation for sprint performance. The significant difference between African-American sprinters and African-American controls suggests that the maternal admixture may play a role in sprint performance.

Identifying genotype specific elevated-risk areas and associated herd risk factors for bovine tuberculosis spread in British cattle.

Bovine tuberculosis (bTB) is a chronic zoonosis with major health and economic impact on the cattle industry. Despite extensive control measures in cattle and culling trials in wildlife, the reasons behind the expansion of areas with high incidence of bTB breakdowns in Great Britain remain unexplained. By balancing the importance of cattle movements and local transmission on the observed pattern of cattle outbreaks, we identify areas at elevated risk of infection from specific Mycobacterium bovis genotypes. We show that elevated-risk areas (ERAs) were historically more extensive than previously understood, and that cattle movements alone are insufficient for ERA spread, suggesting the involvement of other factors. For all genotypes, we find that, while the absolute risk of infection is higher in ERAs compared to areas with intermittent risk, the statistically significant risk factors are remarkably similar in both, suggesting that these risk factors can be used to identify incipient ERAs before this is indicated by elevated incidence alone. Our findings identify research priorities for understanding bTB dynamics, improving surveillance and guiding management to prevent further ERA expansion.

Hypocholesterolemic activity of synthetic and natural tocotrienols.

Tocotrienols are farnesylated benzopyran natural products that exhibit hypocholesterolemic activity in vitro and in vivo. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase by a process distinct from other known inhibitors of cholesterol biosynthesis. An efficient synthetic route to tocotrienols and their isolation from palm oil distillate using an improved procedure is presented. gamma-Tocotrienol exhibits a 30-fold greater activity toward cholesterol biosynthesis inhibition compared to alpha-tocotrienol in HepG2 cells in vitro. The synthetic (racemic) and natural (chiral) tocotrienols exhibit nearly identical cholesterol biosynthesis inhibition and HMG-CoA reductase suppression properties as demonstrated in vitro and in vivo.

Inhibitors of cholesterol biosynthesis. 2. Hypocholesterolemic and antioxidant activities of benzopyran and tetrahydronaphthalene analogues of the tocotrienols.

Tocotrienols exhibit antioxidant and cholesterol-biosynthesis-inhibitory activities and may be of value as antiatherosclerotic agents. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase (HMGR) in a manner mimicking the action of putative non-sterol feedback inhibitors. The in vitro cholesterol-biosynthesis-inhibitory and HMGR-suppressive activities in HepG2 cells of an expanded series of benzopyran and tetrahydronaphthalene isosteres and the hypocholesterolemic activity of selected compounds assessed in orally dosed chickens are presented. Preliminary antioxidant data of these compounds have been obtained using cyclic voltammetry and Cu-induced LDL oxidation assays. The farnesyl side chain and the methyl/hydroxy substitution pattern of gamma-tocotrienol deliver a high level of HMGR suppression, unsurpassed by synthetic analogues of the present study. In orally dosed chickens, 8-bromotocotrienol (4o), 2-desmethyltocotrienol (4t), and the tetrahydronaphthalene derivative 35 exhibit a greater degree of LDL cholesterol lowering than the natural tocotrienols.

Motor responsivity during habituation testing of normal human fetuses.

Features of fetal motor responsivity include both the magnitude of the startle response elicited by a single stimulus (i.e., basal reactivity) and the ease by which responding to successive stimuli is inhibited (i.e., habituation). We examined basal motor reactivity and habituation of the motor response in 56 normal human fetuses between 34 and 40 weeks of gestation. Testing consisted of 8 trials of a 1-sec vibroacoustic stimulus (VAS) with a 10-sec interstimulus interval. A score of 0-10 was assigned for each trial based on subjective assessment of intensity and duration of the fetal motor response. Measures of habituation included the ratio of responding after a fixed number of trials divided by the initial response, and the rate of change in the behavioral response over trials. No relationship was found between the rate of motor habituation and either basal reactivity, gestational age, or prestimulus fetal heart rate (FHR) variability. In contrast, more mature fetuses responded less intensely to the first stimulus than did their younger counterparts (r = -0.329, p = 0.005), and fetuses who were initially in a quiet state exhibited a more vigorous startle response as compared to fetuses who were initially in a more active state (r = -0.372, p = 0.001). The relationship between basal reactivity and prestimulus FHR variability was statistically significant even after controlling for gestational age (r = 0.295, p = 0.01). These findings may have important clinical implications regarding the appearance in early life of certain behavioral tendencies such as temperament.