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Background: SMA1 is a neurodegenerative disease caused by bi-allelic survival motor neuron 1 gene (SMN1) deletion/mutation. In the phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA1 patients. We report preliminary data of STR1VE, a pivotal study (NCT03306277) evaluating efficacy and safety of a one-time intravenous AVXS-101 infusion. Methods: STR1VE is a phase 3, multicenter, open-label, single-arm study in SMA1 patients aged <6 months (bi-allelic SMN1 loss, 2xSMN2). Primary outcomes: independent sitting for ≥30 seconds (18 months) and survival (14 months). Secondary outcomes: ability to thrive and ventilatory support (18 months). Exploratory outcomes: CHOP-INTEND and Bayley Scales of Infant and Toddler Development scores. Results: Enrollment is complete with 22 patients dosed. Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support, and all exclusively fed by mouth. Mean baseline CHOP-INTEND score was 32.6 (17.0–52.0), which increased 6.9 (-4.0–16.0, n=20), 10.4 (2.0–18.0, n=12), and 11.6 (-3.0–23.0, n=9) points at 1, 2, and 3 months; updates provided at congress. Conclusions: Preliminary data from STR1VE show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.
The cypress bark beetle, Phloeosinus armatus, is a common element of the dying cypress tree system in East-Mediterranean countries. Adult beetles congregate for breeding on this ephemeral resource. We studied three traits that characterize this beetle's sexual behavior and linked them to its reproductive success: mating system, mate choice, and parental care. We found that the females are the ‘pioneering sex’, excavating the mating chamber. The average female is slightly larger than the male, and female and male body size is correlated, demonstrating size-assortative mating. The time it takes for a male to enter the mating chamber is positively correlated with female size and negatively correlated with its own size, which is perhaps responsible for this assortative mating. Males remain in the gallery during the period of oviposition, gradually leaving soon after the eggs hatch. The number of eggs laid and tunnel length are positively correlated with male body size. Finally, in the presence of both parents, more eggs are laid than when the female alone is present, demonstrating the important contribution of biparental care for reproductive success. We suggest that the interaction between a monogamous mating system, assortative mating, and biparental care contributes to reproductive success.
We present the KMOS (K-band Multi-Object Spectrograph) Cluster and VIRIAL (VLT IRIFU Absorption Line) Guaranteed Time Observation (GTO) programs. KMOS provides 24 arms each feeding an integral field unit (14×14 spaxels of 0.2″ pixels) for IZ, YJ, H and K band near infrared (NIR) medium resolution spectroscopy (R ∼ 3500). Targets are selected from a 7.2′ diameter patrol field. Ultra-deep spectroscopy of ∼ 80 early-type cluster galaxies (∼ 20hr on source) and ∼ 200 (∼ 10hr on source) early-type field galaxies at 1 < z < 2 will dramatically improve the situation at z > 1 for which measurements of stellar velocity dispersions and absorption indices are limited to a few, often relatively young passively evolving galaxies (e.g. Bezanson 2013). In ESO Periods P92 and P93, 15 nights worth of data has been collected for KMOS-Clusters and 6 nights for VIRIAL: this will be supplemented with more data in upcoming semesters. All galaxies have multiband HST imaging including existing or upcoming WFC3 IR imaging, providing stellar mass maps and sizes. Combined with our dispersion measurements, this will allow us to examine the fundamental plane and the dynamical mass of a large sample of z > 1 galaxies for the first time, for both cluster and field galaxies.
KMOS is a cryogenic infrared spectrograph fed by twentyfour deployable integral field units that patrol a 7.2 arcminute diameter field of view at the Nasmyth focus of the ESO VLT. It is well suited to the study of galaxy clusters at 1 < z < 2 where the well understood features in the restframe V-band are shifted into the KMOS spectral bands. Coupled with HST imagining, KMOS offers a window on the critical epoch for galaxy evolution, 7-10 Gyrs ago, when the key properties of cluster galaxies were established. We aim to investigate the size, mass, morphology and star formation history of galaxies in the clusters. Here we describe the instrument, discuss the status of the observations and report some preliminary results.
To study whether employees who disclose a psychiatric diagnosis, such as depression risk stigmatisation and discrimination at the workplace.
Randomised experimental study with 748 managers from German companies incorporating four case vignettes displaying an employee with different ‘diagnoses’ (depression, burnout, private crisis and thyroid dysfunction), but identical unspecific complaints. Main outcome measures were the managers' attitudes and their impact on stigmatisation with respect to job performance.
In nearly all aspects of job performance, the diagnosis depression (psychiatric disorder) was seen as more critical than the diagnosis of a thyroid dysfunction (somatic disease). The diagnosis ‘burnout’ did not prove to be less stigmatising than ‘depression’. Likewise ‘private crisis’ was rated less favourably than thyroid dysfunction.
Therefore, employees have to evaluate if they disclose their psychiatric disorder or if they conceal it as a somatic illness.
Despite good clinical evidence, depot antipsychotics are only seldom prescribed to patients with first episode schizophrenia. The present study aims at investigating psychiatrists’ reasons for this reservation.
We surveyed 198 psychiatrists on their attitude toward offering depot treatment to first episode patients (FEP). Participants scored the extent of influence of individual factors on their decision on a seven-point-scale, additional data on their prescription practice and estimation of the relapse risk of FEP were collected.
Psychiatrists reported that only three out of 12 factors were of influence. These were the limited availability of different second generation antipsychotic depot drugs, the frequent rejection of the depot offer by the patients and the patients’ skepticism based on the lack in experience of a relapse.
There is actually little specific reason for not prescribing depot to FEP according to the current survey. For those factors being reported to be of influence, psychoeducation, including profound information on depot treatment, the development of additional SGA depot drugs and the standard offer of depot treatment to all FEP in a shared-decision-making may be considered.
Diagnostic errors can have tremendous consequences because they can result in a fatal chain of wrong decisions. Experts assume that physicians' desire to confirm a preliminary diagnosis while failing to seek contradictory evidence is an important reason for wrong diagnoses. This tendency is called ‘confirmation bias’.
To study whether psychiatrists and medical students are prone to confirmation bias and whether confirmation bias leads to poor diagnostic accuracy in psychiatry, we presented an experimental decision task to 75 psychiatrists and 75 medical students.
A total of 13% of psychiatrists and 25% of students showed confirmation bias when searching for new information after having made a preliminary diagnosis. Participants conducting a confirmatory information search were significantly less likely to make the correct diagnosis compared to participants searching in a disconfirmatory or balanced way [multiple logistic regression: odds ratio (OR) 7.3, 95% confidence interval (CI) 2.53–21.22, p<0.001; OR 3.2, 95% CI 1.23–8.56, p=0.02]. Psychiatrists conducting a confirmatory search made a wrong diagnosis in 70% of the cases compared to 27% or 47% for a disconfirmatory or balanced information search (students: 63, 26 and 27%). Participants choosing the wrong diagnosis also prescribed different treatment options compared with participants choosing the correct diagnosis.
Confirmatory information search harbors the risk of wrong diagnostic decisions. Psychiatrists should be aware of confirmation bias and instructed in techniques to reduce bias.
Galaxy-galaxy interactions and large scale galaxy bars are usually considered as the two main mechanisms for driving gas to the centres of galaxies. By using large samples of galaxy pairs and visually classified bars from the Sloan Digital Sky Survey (SDSS), we compare the relative efficiency of gas inflows from these two processes. We use two indicators of gas inflow: star formation rate (SFR) and gas phase metallicity, which are both measured relative to control samples. Whereas the metallicity of galaxy pairs is suppressed relative to its control sample of isolated galaxies, galaxies with bars are metal-rich for their stellar mass by 0.06 dex over all stellar masses. The SFRs of both the close galaxy pairs and the barred galaxies are enhanced by ~60%, but in the bars the enhancement is only seen at stellar masses M∗ > 1010 M⊙. Taking into account the relative frequency of bars and pairs, we estimate that at least three times more central star formation is triggered by bars than by interactions.
Los intentos de suicidio médicamente graves se han reconocido como el predictor más importante de suicidio. Recientemente se ha encontrado que la Escala Informatizada de Riesgo de Suicidio basada en redes neurales de retropropagación (CSRS-BP) es eficaz en la detección de historias clínicas de pacientes que realizaron intentos de suicidio médicamente graves (ISMG).
Validar la CSRS-BP: 1) utilizándola con pacientes en lugar de con historias clínicas; 2) comparando la capacidad de psiquiatras expertos para detectar ISMG utilizando la lista de la CSRS, y 3) comparando los resultados del Estimador de Riesgo para el Suicidio (RES) y la Escala de autoevaluación de Riesgo de Suicidio (SRS) con la CSRS-BP.
Profesionales clínicos diagnosticaron a 250 pacientes psiquiátricos hospitalizados (35 con ISMG y 215 sin ISMG) utilizando la SCID del DSM IV. Tres psiquiatras expertos cumplimentaron la lista de la CSRS y el RES para cada paciente, y los pacientes rellenaron la escala de evaluación de autoinforme SRS. La CSRS-BP se pasó en máquina para cada paciente. Otros cinco psiquiatras expertos evaluaron las listas de la CSRS y estimaron la probabilidad de ISMG para cada paciente. Se hicieron comparaciones de las tasas de sensibilidad y especificidad entre la CSRS-BP, las escalas de evaluación y los expertos.
Inicialmente, la CSRS-BP, el RES, la SRS y los expertos obtuvieron malos resultados. Aunque las tasas de sensibilidad y especificidad mejoraron significativamente (de dos a cuatro veces) después de la inclusión de información con respecto al número de intentos previos de suicidio en el conjunto de datos de entrada, los resultados todavía no eran significativos.
La CSRS-BP, que tuvo mucho éxito en la detección de historias clínicas de pacientes con ISMG, no detectó a los pacientes con ISMG en entrevistas cara a cara. La información con respecto a los intentos de suicidio anteriores es un predictor importante de ISMG, pero es insuficiente para su detección en los pacientes individuales. La tasa de detección de la SRS y la escala RES fue también mala y, por tanto, no pudieron identificar a los pacientes con ISMG o utilizarse para validar la CSRS-BP.
Medically serious suicide attempts have been recognized as the most important predictor of suicide. The Computerized Suicide Risk Scale based on backpropagation neural networks (CSRS-BP) has been recently found efficient in the detection of records of patients who performed medically serious suicide attempts (MSSA).
To validate the CSRS-BP by: 1) using the CSRS-BP with patients instead of records; 2) comparing the ability of expert psychiatrists to detect MSSA, using the CSRS checklist; and 3) comparing the results of the Risk Estimator for Suicide (RES) and the self-rating Suicide Risk Scale (SRS) with the CSRS-BP.
Two hundred fifty psychiatric inpatients (35 MSSA and 215 non-MSSA) were diagnosed by clinicians using the SCID DSM-IV. Three expert psychiatrists completed the CSRS checklist, and the RES for each patient, and the patients completed the self-report SRS assessment scale. The CSRS-BP was run for each patient. Five other expert psychiatrists assessed the CSRS checklists and estimated the probability of MSSA for each patient. Comparisons of sensitivity and specificity rates between CSRS-BP, assessment scales and experts were done.
Initially, the CSRS-BP, RES, SRS, and experts performed poorly. Although sensitivity and specificity rates significantly improved (two to four times) after the inclusion of information regarding the number of previous suicide attempts in the input data set, results still remained insignificant.
The CSRS-BP, which was very successful in the detection of MSSA patient records, failed to detect MSSA patients in face-to-face interviews. Information regarding previous suicide attempts is an important MSSA predictor, but remains insufficient for the detection of MSSA in individual patients. The detection rate of the SRS and RES scales was also poor and could therefore not identify MSSA patients or be used to validate the CSRS-BP.
Nanocomposites were made using deionized gelatin filled with well-dispersed nanoscale alumina particles. Scratch tests on the nanocomposite films showed substantially improved scratch resistance. Tensile tests revealed increases in both modulus and tensile strength of the nano-filled gelatin films accompanied by a decrease in strain-to-failure. The increase in modulus and strength reduced the degree of plastic deformation during scratch testing, but the onset of periodic cracking in the scratch track was unaffected. Optical transmittance measurements of the gelatin composite showed that the films retained transparency in the visible light range.
We have explored a new technology based on chemically induced phase separation that yields porous epoxies and cyanurates with a closed cell morphology and micrometer sized pores with a narrow pore size distribution. When the precursor monomers are cured in the presence of a low molecular weight liquid, the desired morphology results from a phase separation and a chemical quench. After phase separation, the porosity is achieved by thermal removal of the secondary liquid phase, specifically by diffusion through the crosslinked matrix. In respect to the thermodynamics and kinetics, the origin of the phase separation process can be identified as nucleation and growth. The influence of internal and external reaction parameters, such as chemical nature of the low molecular weight liquid, its concentration and the curing temperature on the final morphology are presented. Thus, the morphology can be controlled ranging from a monomodal to bimodal pore size distribution with pore sizes inbetween 1 to 10 μm. These porous thermosets are characterized by a significantly lower density, without any loss in thermal stability compared to the neat matrix. Such new materials demonstrate great interest for lowering the dielectric constant and for improving the fundamental understanding of the role of voids in stress relaxation and toughening.
The most important crop plants of the world belong to the monocotyledonous grasses. From the perspective of genetically transforming these successful outdoors plants with new genes, they have properties in common. The tissues of these grasses lack what is called the wound response – the characteristic of the cells at a site of physical damage to proliferate and form calloid protective tissue – the cereal tissue rather seals the wound site by lignification and sclerification of the cells.
This alternative strategy in reaction to wounding seems to be the basis of the recalcitrance of cereal plants to the manipulations of the experimentalist. The two most commonly used gene transfer techniques utilize either the capability of Agrobacterium to mate with plants or the capacity of a naked plant cell (protoplast), where DNA can be introduced by physical means, to regenerate its cell wall, start to divide and finally to differentiate into a mature plant. Neither of these methods functions easily for the cereal grasses. Agrobacteria deliver their transferred DNA into cells at a wound site – destined to deteriorate. Protoplasts of cereal plants have been very hard to regenerate and especially to retain their capacity to differentiate after regeneration. This situation has led to the development of alternative, often very imaginative, gene transfer techniques. The literature of cereal transformation is littered with reports of exotic methods that mostly have given ambiguous results and are very hard to repeat.
The Zn substitution on Cu(2) sites in YBa2(Cu1-yZny)3O6+x materials is most probably limited to yzn ≈ 0.04. Results of neutron diffraction associated with NMR and μ+SR results reveal ; i) a lowering of TN in the pure AF region x≤0.20 due to a dilution effect of the antiferromagnetic lattice by a static non magnetic impurity, ii) the existence of a non conventionnal magnetic behavior within the intermediate region x≥0.35 characterized by an unusual temperature dependance of magnetic intensities, a reentrancy and the existence of diffuse magnetic scattering (this region is much broader in oxygen composition for Zn-doped than for pure YBCO),iii) an unusual spin dynamics in the "doped A-F phase" which corresponds to a coupling of magnetic excitations to the hole dynamics.
To compare the safety and antidepressant efficacy of paroxetine, imipramine, and placebo, data from six centres using the same protocol were pooled. A double-blind parallel-group design was used, with therapy lasting six weeks. From week 2 onwards, both the 240 paroxetine-treated and the 237 imipramine-treated patients were significantly different from the 240 placebo-treated patients, but no different from each other. Side-effects with paroxetine were less likely to lead to drop-out than with imipramine. Paroxetine had a possible earlier antidepressant effect than imipramine, and a possible earlier beneficial effect on anxiety symptoms associated with depression.
Fully electromagnetic, relativistic, two-dimensional, particle-in-cell (PIC) simulations of barrel-type and extractor-type Applied-B ion diodes have increased our confidence in the design of present and future diodes for the Particle Beam Fusion Accelerator II (PBFA II). In addition, the data from various experiments on Pro to I, Proto II, and PBFA I Applied-B ion diodes are inconsistent with previous models of diode operation, based on anode-cathode gap closure from expanding plasmas. A new model has been devised and applied to the PBFA II diode to explain the diode impedance and its time history, and to suggest methods for controlling the impedance.
Electrodes for FNS were fabricated by photolithographic techniques from foils of Mo, Ta, and stainless steel with lateral dimensions of 1–3 mm and thickness of about 50 μm. More recent designs have utilized a Si carrier with either a Pt or diffused Si track terminated by Au electrodes. Biocompatibility studies conducted on frogs and rabbits indicate good stability of electrodes coated with SiO by plasma deposition. Carriers did not move after implantation and did not show signs of corrosion. The diffused Si design is now preferred since electrode tracks are sub-surface, tracks may be electrically and biologically insulated by SiO2, all fabrication steps are compatible with standard integrated circuit processing such that electronics may be integrated on the carrier with the electrode tracks, and small dimensions are easily attained.