Satisfaction survey with DNA cards method to collect genetic samples for pharmacogenetics studies

BACKGROUND: Pharmacogenetic studies are essential in understanding the interindividual variability of drug responses. DNA sample collection for genotyping is a critical step in genetic studies. A method using dried blood samples from finger-puncture, collected on DNA-cards, has been described as an alternative to the usual venepuncture technique. The purpose of this study is to evaluate the implementation of the DNA cards method in a multicentre clinical trial, and to assess the degree of investigators' satisfaction and the acceptance of the patients perceived by the investigators. METHODS: Blood samples were collected on DNA-cards. The quality and quantity of DNA recovered were analyzed. Investigators were questioned regarding their general interest, previous experience, safety issues, preferences and perceived patient satisfaction. RESULTS: 151 patients' blood samples were collected. Genotyping of GST polymorphisms was achieved in all samples (100%). 28 investigators completed the survey. Investigators perceived patient satisfaction as very good (60.7%) or good (39.3%), without reluctance to finger puncture. Investigators preferred this method, which was considered safer and better than the usual methods. All investigators would recommend using it in future genetic studies. CONCLUSION: Within the clinical trial setting, the DNA-cards method was very well accepted by investigators and patients (in perception of investigators), and was preferred to conventional methods due to its ease of use and safety

Abnormal motor activity during anaesthesia in a dog: a case report

Seizures or convulsions that occur during anaesthesia in veterinary patients are infrequently reported in the literature. Consequently, the incidence of such events is unknown. Several drugs commonly used in clinical veterinary anaesthesia have been shown to induce epileptiform activity in both human clinical patients and experimental candidates. The present case report describes convulsions in a four-year old male Bernese mountain dog during maintenance of anaesthesia with isoflurane after premedication with acepromazine and methadone followed by co-induction with propofol and ketamine. The dog had no history of previous convulsions. The use of several sedative and anaesthetic drugs makes it difficult to find one single causative pharmaceutical

Head Circumference of Infants Born to Mothers with Different Educational Levels; The Generation R Study

Objective: Head circumference (HC) reflect growth and development of the brain in early childhood. It is unknown whether socioeconomic differences in HC are present in early childhood. Therefore, we investigated the association between socioeconomic position (SEP) and HC in early childhood, and potential underlying factors. Methods: The study focused on Dutch children born between April 2002 and January 2006 who participated in The Generation R Study, a population-based prospective cohort study in Rotterdam, the Netherlands. Maternal educational level was used as indicator of SEP. HC measures were concentrated around 1, 3, 6 and 11 months. Associations and explanatory factors were investigated using linear regression analysis, adjusted for potential mediators. Results: The study included 3383 children. At 1, 3 and 6 months of age, children of mothers with a low education had a smaller HC than those with a high education (difference at 1 month: -0.42 SD; 95% CI: -0.54,-0.30; at 3 months: -0.27 SD; 95% CI -0.40,-0.15; and at 6 months: -0.13 SD; 95% CI -0.24,-0.02). Child's length and weight could only partially explain the smaller HC at 1 and 3 months of age. At 6 months, birth weight, gestational age and parental height explained the HC differences. At 11 months, no HC differences were found. Conclusion: Educational inequalities in HC in the first 6 months of life can be mainly explained by pregnancy-related factors, such as birth weight and gestational age. These findings further support public health policies to prevent negative birth outcomes in lower socioeconomic groups

Probing inner and outer disk misalignments in transition disks

This is the final version. Available from EDP Sciences via the DOI in this record. All codes used for the data analysis, as well as example data files, are available at https://github.com/18alex96/disk_misalignmentsContext. Transition disks are protoplanetary disks with dust-depleted cavities, possibly indicating substantial clearing of their dust content by a massive companion. For several known transition disks, dark regions interpreted as shadows have been observed in scattered light imaging and are hypothesized to originate from misalignments between distinct regions of the disk. Aims. We aim to investigate the presence of misalignments in transition disks. We study the inner disk (10 au). Methods. We fit simple parametric models to the visibilities and closure phases of the GRAVITY data to derive the inclination and position angle of the inner disks. The outer disk geometries were derived from Keplerian fits to the ALMA velocity maps and compared to the inner disk constraints. We also predicted the locations of expected shadows for significantly misaligned systems. Results. Our analysis reveals six disks to exhibit significant misalignments between their inner and outer disk structures. The predicted shadow positions agree well with the scattered light images of HD 100453 and HD 142527, and we find supporting evidence for a shadow in the south of the disk around CQ Tau. In the other three targets for which we infer significantly misaligned disks, V1247 Ori, V1366 Ori, and RY Lup, we do not see any evident sign of shadows in the scattered light images. The scattered light shadows observed in DoAr 44, HD 135344 B, and HD 139614 are consistent with our observations, yet the underlying morphology is likely too complex to be described properly by our models and the accuracy achieved by our observations. Conclusions. The combination of near infrared and submillimeter interferometric observations allows us to assess the geometries of the innermost disk regions and those of the outer disk. Whereas we can derive precise constraints on the potential shadow positions for well-resolved inner disks around Herbig Ae/Be stars, the large statistical uncertainties for the marginally resolved inner disks around the T Tauri stars of our sample make it difficult to extract conclusive constraints for the presence of shadows in these systems.European Research CouncilEuropean Research CouncilEuropean Research CouncilEuropean Research CouncilEuropean Research CouncilDeutsche Forschungsgemeinschaft (DFG, German Research Foundation)Science Foundation Irelan

Spiroplasma Bacteria Enhance Survival of Drosophila hydei Attacked by the Parasitic Wasp Leptopilina heterotoma

Maternally-transmitted associations between endosymbiotic bacteria and insects are ubiquitous. While many of these associations are obligate and mutually beneficial, many are facultative, and the mechanism(s) by which these microbes persist in their host lineages remain elusive. Inherited microbes with imperfect transmission are expected to be lost from their host lineages if no other mechanisms increase their persistence (i.e., host reproductive manipulation and/or fitness benefits to host). Indeed numerous facultative heritable endosymbionts are reproductive manipulators. Nevertheless, many do not manipulate reproduction, so they are expected to confer fitness benefits to their hosts, as has been shown in several studies that report defense against natural enemies, tolerance to environmental stress, and increased fecundity.We examined whether larval to adult survival of Drosophila hydei against attack by a common parasitoid wasp (Leptopilina heterotoma), differed between uninfected flies and flies that were artificially infected with Spiroplasma, a heritable endosymbiont of Drosophila hydei that does not appear to manipulate host reproduction. Survival was significantly greater for Spiroplasma-infected flies, and the effect of Spiroplasma infection was most evident during the host's pupal stage. We examined whether or not increased survival of Spiroplasma-infected flies was due to reduced oviposition by the wasp (i.e., pre-oviposition mechanism). The number of wasp eggs per fly larva did not differ significantly between Spiroplasma-free and Spiroplasma-infected fly larvae, suggesting that differential fly survival is due to a post-oviposition mechanism.Our results suggest that Spiroplasma confers protection to D. hydei against wasp parasitism. This is to our knowledge the first report of a potential defensive mutualism in the genus Spiroplasma. Whether it explains the persistence and high abundance of this strain in natural populations of D. hydei, as well as the widespread distribution of heritable Spiroplasma in Drosophila and other arthropods, remains to be investigated

Witnessing Violence Toward Siblings: An Understudied but Potent Form of Early Adversity

Research on the consequences of witnessing domestic violence has focused on inter-adult violence and most specifically on violence toward mothers. The potential consequences of witnessing violence to siblings have been almost entirely overlooked. Based on clinical experience we sought to test the hypothesis that witnessing violence toward siblings would be as consequential as witnessing violence toward mothers. The community sample consisted of unmedicated, right-handed, young adults who had siblings (n = 1,412; 62.7% female; 21.8±2.1 years of age). History of witnessing threats or assaults to mothers, fathers and siblings, exposure to parental and sibling verbal abuse and physical abuse, sexual abuse and sociodemographic factors were assessed by self-report. Symptoms of depression, anxiety, somatization, anger-hostility, dissociation and ‘limbic irritability’ were assessed by rating scales. Data were analyzed by multiple regression, with techniques to gauge relative importance; logistic regression to assess adjusted odds ratios for clinically-significant ratings; and random forest regression using conditional trees. Subjects reported witnessing violence to siblings slightly more often than witnessing violence to mothers (22% vs 21%), which overlapped by 51–54%. Witnessing violence toward siblings was associated with significant effects on all ratings. Witnessing violence toward mother was not associated with significant effects on any scale in these models. Measures of the relative importance of witnessing violence to siblings were many fold greater than measures of importance for witnessing violence towards mothers or fathers. Mediation and structural equation models showed that effects of witnessing violence toward mothers or fathers were predominantly indirect and mediated by changes in maternal behavior. The effects of witnessing violence toward siblings were more direct. These findings suggest that greater attention be given to the effects of witnessing aggression toward siblings in studies of domestic violence, abuse and early adversity

GRAIN GROWTH in the CIRCUMSTELLAR DISKS of the YOUNG STARS CY Tau and DoAr 25

We present new results from the Disks@EVLA program for two young stars: CY Tau and DoAr 25. We trace continuum emission arising from their circusmtellar disks from spatially resolved observations, down to tens of AU scales, at {\lambda} = 0.9, 2.8, 8.0, and 9.8 mm for DoAr25 and at {\lambda} = 1.3, 2.8, and 7.1 mm for CY Tau. Additionally, we constrain the amount of emission whose origin is different from thermal dust emission from 5 cm observations. Directly from interferometric data, we find that observations at 7 mm and 1 cm trace emission from a compact disk while millimeter-wave observations trace an extended disk structure. From a physical disk model, where we characterize the disk structure of CY Tau and DoAr 25 at wavelengths shorter than 5 cm, we find that (1) dust continuum emission is optically thin at the observed wavelengths and over the spatial scales studied, (2) a constant value of the dust opacity is not warranted by our observations, and (3) a high-significance radial gradient of the dust opacity spectral index, {\beta}, is consistent with the observed dust emission in both disks, with low-{\beta} in the inner disk and high-{\beta} in the outer disk. Assuming that changes in dust properties arise solely due to changes in the maximum particle size (amax), we constrain radial variations of amax in both disks, from cm-sized particles in the inner disk (R 80 AU). These observational constraints agree with theoretical predictions of the radial-drift barrier, however, fragmentation of dust grains could explain our amax(R) constraints if these disks have lower turbulence and/or if dust can survive high-velocity collisions

Multiwavelength analysis for interferometric (sub-)mm observations of protoplanetary disks: Radial constraints on the dust properties and the disk structure

Theoretical models of grain growth predict dust properties to change as a function of protoplanetary disk radius, mass, age and other physical conditions. We lay down the methodology for a multi-wavelength analysis of (sub-)mm and cm continuum interferometric observations to constrain self-consistently the disk structure and the radial variation of the dust properties. The computational architecture is massively parallel and highly modular. The analysis is based on the simultaneous fit in the uv-plane of observations at several wavelengths with a model for the disk thermal emission and for the dust opacity. The observed flux density at the different wavelengths is fitted by posing constraints on the disk structure and on the radial variation of the grain size distribution. We apply the analysis to observations of three protoplanetary disks (AS 209, FT Tau, DR Tau) for which a combination of spatially resolved observations in the range ~0.88mm to ~10mm is available (from SMA, CARMA, and VLA), finding evidence of a decreasing maximum dust grain size (a_max) with radius. We derive large a_max values up to 1 cm in the inner disk between 15 and 30 AU and smaller grains with a_max~1 mm in the outer disk (R > 80AU). In this paper we develop a multi-wavelength analysis that will allow this missing quantity to be constrained for statistically relevant samples of disks and to investigate possible correlations with disk or stellar parameters

Biophysical Characteristics Reveal Neural Stem Cell Differentiation Potential

Distinguishing human neural stem/progenitor cell (huNSPC) populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers

The Multiplanet System TOI-421*: A Warm Neptune and a Super Puffy Mini-Neptune Transiting a G9 V Star in a Visual Binary*

We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations—comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echellé Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution Échelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements—and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of Pb = 5.19672 ± 0.00049 days, a mass of Mb = 7.17 ± 0.66 M⊕, and a radius of Rb = ${2.68}_{-0.18}^{+0.19}$ R⊕, whereas the outer warm Neptune, TOI-421 c, has a period of Pc = 16.06819 ± 0.00035 days, a mass of Mc = ${16.42}_{-1.04}^{+1.06}$ M⊕, a radius of Rc = ${5.09}_{-0.15}^{+0.16}$ R⊕, and a density of ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3. With its characteristics, the outer planet (ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Lyα transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed