Remarks on the Central Limit Theorem for Non-Convex Bodies

In this note, we study possible extensions of the Central Limit Theorem for non-convex bodies. First, we prove a Berry-Esseen type theorem for a certain class of unconditional bodies that are not necessarily convex. Then, we consider a widely-known class of non-convex bodies, the so-called p-convex bodies, and construct a counter-example for this class

Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour

Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role

Associations of neighborhood problems and neighborhood social cohesion with mental health and health behaviors: the Multi-Ethnic Study of Atherosclerosis

Few studies have investigated the specific features implicated in neighborhood-health associations. We examined associations between measures of neighborhood problems and neighborhood social cohesion with depression, smoking, drinking, and walking for exercise in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Neighborhoods were characterized according to participant self-report and aggregated measures based on other MESA participants. Individuals living in the least problematic neighborhoods were significantly less likely to be depressed, to smoke, or to drink. Less socially cohesive neighborhoods were associated with increased depression, smoking, and not walking for exercise. Results persisted after adjusting for individual-level variables. Each measure appeared to capture distinct features of the neighborhood and associations did not differ by race/ethnicity. Results for neighborhood problems were robust to the use of aggregate measures but results for social cohesion generally were not. Future work should determine the health effect of modifying specific features of the neighborhood context.http://deepblue.lib.umich.edu/bitstream/2027.42/60951/1/Assoc of neigh problems & neigh social cohesion MESApdf.pd

Fetal heart rate and fetal heart rate variability in Lipizzaner broodmares

Monitoring fetal heart rate (FHR) and fetal heart rate variability (FHRV) helps to understand and evaluate normal and pathological conditions in the foal. The aim of this study was to establish normal heart rate reference values for the ongoing equine pregnancy and to perform a heart rate variability (HRV) time-domain analysis in Lipizzaner mares. Seventeen middle- and late-term (days 121–333) pregnant Lipizzaner mares were examined using fetomaternal electrocardiography (ECG). The mean FHR (P = 0.004) and the standard deviation of FHR (P = 0.012) significantly decreased during the pregnancy. FHR ± SD values decreased from 115 ± 35 to 79 ± 9 bpm between months 5 and 11. Our data showed that HRV in the foal decreased as the pregnancy progressed, which is in contrast with the findings of earlier equine studies. The standard deviation of normal-normal intervals (SDNN) was higher (70 ± 25 to 166 ± 108 msec) than described previously. The root mean square of successive differences (RMSSD) decreased from 105 ± 69 to 77 ± 37 msec between the 5th and 11th month of gestation. Using telemetric ECG equipment, we could detect equine fetal heartbeat on day 121 for the first time. In addition, the large differences observed in the HR values of four mare-fetus pairs in four consecutive months support the assumption that there might be ‘high-HR’ and ‘low-HR’ fetuses in horses. It can be concluded that the analysis of FHR and FHRV is a promising tool for the assessment of fetal well-being but the applicability of these parameters in the clinical setting and in studs requires further investigation

Human Analogue Safe Haven Effect of the Owner : Behavioural and Heart Rate Response to Stressful Social Stimuli in Dogs

The secure base and safe haven effects of the attachment figure are central features of the human attachment theory. Recently, conclusive evidence for human analogue attachment behaviours in dogs has been provided, however, the owner’s security-providing role in danger has not been directly supported. We investigated the relationship between the behavioural and cardiac response in dogs (N = 30) while being approached by a threatening stranger in separation vs. in the presence of the owner, presented in a balanced order. Non-invasive telemetric measures of heart rate (HR) and heart rate variability (HRV) data during the threatening approaches was compared to periods before and after the encounters. Dogs that showed distress vocalisation during separation (N = 18) and that growled or barked at the stranger during the threatening approach (N = 17) were defined as behaviourally reactive in the given situation. While characteristic stress vocalisations were emitted during separations, the absence of the owner did not have an effect on dogs’ mean HR, but significantly increased the HRV. The threatening approach increased dogs’ mean HR, with a parallel decrease in the HRV, particularly in dogs that were behaviourally reactive to the encounter. Importantly, the HR increase was significantly less pronounced when dogs faced the stranger in the presence of the owner. Moreover, the test order, whether the dog encountered the stranger first with or without its owner, also proved important: HR increase associated with the encounter in separation seemed to be attenuated in dogs that faced the stranger first in the presence of their owner. We provided evidence for human analogue safe haven effect of the owner in a potentially dangerous situation. Similarly to parents of infants, owners can provide a buffer against stress in dogs, which can even reduce the effect of a subsequent encounter with the same threatening stimuli later when the owner is not present

Exclusion Performance in Dwarf Goats (Capra aegagrus hircus) and Sheep (Ovis orientalis aries)

Using a comparative approach, we investigated the ability of dwarf goats and sheep to use direct and indirect information about the location of a food reward in an object-choice task. Subjects had to choose between two cups with only one covering a reward. Before making a choice, subjects received information about the baited (direct information) or non-baited cup (indirect information). Both goats and sheep were able to use direct information (presence of food) in the object choice task. After controlling for local enhancement, we found that goats rather than sheep were able to use indirect information (i.e., the absence of food) to find a reward. The actual test setup could not clarify whether individual goats were able to inferentially reason about the content of the baited cup when only shown the content of the non-baited cup or if they simply avoided the empty cup in that situation. As browsing species, feral and wild goats exhibit highly selective feeding behaviour compared to the rather unselective grazing sheep. The potential influence of this species-specific foraging flexibility of goats and sheep for using direct and indirect information to find a food reward is discussed in relation to a higher aversion to losses in food acquisition in goats compared to sheep

Characterization of pulmonary function in 10â18 year old patients with Duchenne muscular dystrophy

Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study in 10â18 year old patients with DMD is the assessment of the inter-correlation between pulmonary function tests (PFTs), their reliability and the association with the general disease stage measured by the Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], forced expiratory volume in one second [FEV1]) and maximum static airway pressures (MIP, MEP) were prospectively collected from 64 DMD patients enrolled in the DELOS trial (ClinicalTrials.gov, number NCT01027884). Baseline PEF percent predicted (PEF%p) was <80% and patients had stopped taking glucocorticoids at least 12 months prior to study start. At baseline PEF%p, FVC%p and FEV1%p correlated well with each other (Spearman's rho: PEF%pâFVC%p: 0.54; PEF%pâFEV1%p: 0.72; FVC%pâFEV1%p: 0.91). MIP%p and MEP%p correlated well with one another (MIP%pâMEP%p: 0.71) but less well with PEF%p (MIP%pâPEF%p: 0.40; MEP%pâPEF%p: 0.41) and slightly better with FVC%p (MIP%pâFVC%p: 0.59; MEP%pâFVC%p: 0.74). The within-subject coefficients of variation (CV) for successive measures were 6.97% for PEF%p, 6.69% for FVC%p and 11.11% for FEV1%p, indicating that these parameters could be more reliably assessed compared to maximum static airway pressures (CV for MIP%p: 18.00%; MEP%p: 15.73%). Yearly rates of PFT decline (placebo group) were larger in dynamic parameters (PEF%p: â8.9% [SD 2.0]; FVC%p: â8.7% [SD 1.1]; FEV1%p: â10.2% [SD 2.0]) than static airway pressures (MIP%p: â4.5 [SD 1.3]; MEP%p: â2.8 [SD 1.1]). A considerable drop in dynamic pulmonary function parameters was associated with loss of upper limb function (transition from Brooke score category 4 to category 5). In conclusion, these findings expand the understanding of the reliability, correlation and evolution of different pulmonary function measures in DMD patients who are in the pulmonary function decline phase

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes

Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy

In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe respiratory complications. Of particular concern are ineffective cough, secretion retention and recurrent respiratory tract infections. In a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD patients 10–18 years of age and not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the loss of respiratory function over a 1-year study period. In a post-hoc analysis of DELOS we found that more patients in the placebo group compared to the idebenone group experienced bronchopulmonary adverse events (BAEs): placebo: 17 of 33 patients, 28 events; idebenone: 6 of 31 patients, 7 events. The hazard ratios (HR) calculated “by patient” (HR 0.33, p = 0.0187) and for “all BAEs” (HR 0.28, p = 0.0026) indicated a clear idebenone treatment effect. The overall duration of BAEs was 222 days (placebo) vs. 82 days (idebenone). In addition, there was also a difference in the use of systemic antibiotics utilized for the treatment of BAEs. In the placebo group, 13 patients (39.4%) reported 17 episodes of antibiotic use compared to 7 patients (22.6%) reporting 8 episodes of antibiotic use in the idebenone group. Furthermore, patients in the placebo group used systemic antibiotics for longer (105 days) compared to patients in the idebenone group (65 days). This post-hoc analysis of DELOS indicates that the protective effect of idebenone on respiratory function is associated with a reduced risk of bronchopulmonary complications and a reduced need for systemic antibiotics