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Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Although sorghum [Sorghum bicolor (L.) Moench ssp. bicolor] is the fifth most important grain crop in terms of global production, no commercial hybrids carry genetically engineered (GE) traits for resistance to insect pests or herbicides due to regulatory concerns about gene flow to weedy relatives. However, non-GE herbicide resistance currently is being developed in grain sorghum and will likely transfer to related weeds. Monitoring the impact of this new nuclear technology on the evolution and invasiveness of related weeds requires a baseline understanding of the population biology of grain sorghum genes once they transfer to in situ weed populations. We previously characterized the rate of gene flow from grain sorghum to shattercane [Sorghum bicolor (L.) Moench nothosubsp. drummondii (Steud.) de Wet ex. Davidse], a conspecific weed relatively common in North America; as well as the ecological fitness of an F1 population when S. bicolor nothosubsp. drummondii was the maternal parent. Here we report the ecological fitness of a S. bicolor nothosubsp. drummondii × S. bicolor ssp. bicolor F2 population relative to its crop and weed parents. Parental and F2 populations were grown in two Nebraska environments in 2012 and 2013. Traits evaluated included overwinter survival, field emergence, biomass production and partitioning at anthesis, total seed production, and 100-seed weight. Results indicated that F2 traits were generally intermediate between the parents, but more similar to S. bicolor nothosubsp. drummondii than to grain sorghum. The one exception was overwinter survival, which was nearly 0% for both the F2 and the grain sorghum parent in these northern environments. Thus, the frequency of crop alleles stably introgressed into S. bicolor nothosubsp. drummondii populations appears to primarily depend on overwinter survival of the F2 and which selective pressures are imposed upon it by the cropping system. These data provide needed baseline information about the environmental fate of nuclear genetic technologies deployed in this important global crop.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
We sought to comprehensively assess the prevalence and outcomes of complications associated with Staphylococcus aureus bacteremia (SAB) in children. Secondarily, prevalence of methicillin resistance and outcomes of complications from methicillin-resistant S. aureus (MRSA) vs. methicillin-susceptible S. aureus SAB were assessed. This is a single-center cross-sectional study of 376 patients ⩽18 years old with SAB in 1990–2014. Overall, 197 (52%) patients experienced complications, the most common being osteomyelitis (33%), skin and soft tissue infection (31%), and pneumonia (25%). Patients with complications were older (median 3 vs. 0·7 years, P = 0·05) and more had community-associated SAB (66% vs. 34%, P = 0·001). Fewer patients with complications had a SAB-related emergency department or hospital readmission (10% vs. 19%, P = 0·014). Prevalence of methicillin resistance increased from 1990–1999 to 2000–2009, but decreased in 2010–2014. Complicated MRSA bacteremia resulted in more intensive care unit admissions (66% vs. 47%, P = 0·03) and led to increased likelihood of having ⩾2 foci (58% vs. 26%, P < 0·001). From multivariate analysis, community-associated SAB increased risk and concurrent infections decreased risk of complications (odds ratio (OR) 1·82 (1·1–3·02), P = 0·021) and (OR 0·58 (0·34–0·97), P = 0·038), respectively. In conclusion, children with SAB should be carefully evaluated for complications. Methicillin resistance remains associated with poor outcomes but have decreased in overall prevalence.
There is a lack of evidence pointing to the efficacy of any specific psychotherapy for adults with anorexia nervosa (AN). The aim of this study was to compare three psychological treatments for AN: Specialist Supportive Clinical Management, Maudsley Model Anorexia Nervosa Treatment for Adults and Enhanced Cognitive Behavioural Therapy.
A multi-centre randomised controlled trial was conducted with outcomes assessed at pre-, mid- and post-treatment, and 6- and 12-month follow-up by researchers blind to treatment allocation. All analyses were intention-to-treat. One hundred and twenty individuals meeting diagnostic criteria for AN were recruited from outpatient treatment settings in three Australian cities and offered 25–40 sessions over a 10-month period. Primary outcomes were body mass index (BMI) and eating disorder psychopathology. Secondary outcomes included depression, anxiety, stress and psychosocial impairment.
Treatment was completed by 60% of participants and 52.5% of the total sample completed 12-month follow-up. Completion rates did not differ between treatments. There were no significant differences between treatments on continuous outcomes; all resulted in clinically significant improvements in BMI, eating disorder psychopathology, general psychopathology and psychosocial impairment that were maintained over follow-up. There were no significant differences between treatments with regard to the achievement of a healthy weight (mean = 50%) or remission (mean = 28.3%) at 12-month follow-up.
The findings add to the evidence base for these three psychological treatments for adults with AN, but the results underscore the need for continued efforts to improve outpatient treatments for this disorder.
Hairworms (Nematomorpha) are a little-known group of parasites, and despite having been represented in the taxonomic literature for over a century, the implementation of molecular genetics in studies of hairworm ecology and evolution lags behind that of other parasitic taxa. In this study, we characterize the genetic diversity of the New Zealand nematomorph fauna and test for genetic structure within the most widespread species found. We provide new mitochondrial and nuclear ribosomal sequence data for three previously described species from New Zealand: Gordius paranensis, Parachordodes diblastus and Euchordodes nigromaculatus. We also present genetic data on a previously reported but undescribed Gordius sp., as well as data from specimens of a new Gordionus sp., a genus new for New Zealand. Phylogenetic analyses of CO1 and nuclear rDNA regions correspond with morphological classification based on scanning electron microscopy, and demonstrate paraphyly of the genus Gordionus and the potential for cryptic species within G. paranensis. Population-level analyses of E. nigromaculatus showed no genetic differentiation among sampling locations across the study area, in contrast to previously observed patterns in known and likely definitive hosts. Taken together, this raises the possibility that factors such as definitive host specificity, intermediate host movement, and passive dispersal of eggs and larvae may influence host–parasite population co-structure in hairworms.
During the last two decades, many attempts were made to determine the global parameters of the Galaxy and to compare the Galaxy to other galaxies (Schmidt-Kaler and Schlosser 1973; de Vaucouleurs and Pence 1978; Gilmore 1984; van der Kruit 1986). While most of these investigations are based on star counts, a detailed overall study by surface photometry, because of the lack of homogeneous high-resolution data, is rare. The last attempt by van der Kruit (1986), based on Pioneer 10 data, suffered from low resolution. The great number of individual structures at low and even intermediate latitudes could not be recognized. Our work (B-band, Hoffmann et al. 1989, this volume; V-band, Schlosser, Schmidt-Kaler, and Schneider 1989; U-Band and R-band photometry, in preparation) provides this homogeneous high-resolution data.
We present a new method, based on surface photometry, which allows one to make the spatial resolution of extinction maps of dark clouds as fine as necessary. Applying this technique to the Coalsack (l = 302°, b = 0°), we derived an extinction map and the dust mass MD = (62 ± 25) M⊙. The density was found to vary ρ ~ r−0.8, typical for stable clouds.
High resolution (0.°25 × 0.°25) surface brightness distribution in V of the southern Milky Way over an area of 200° ≤ l ≤ 60° and of −30° ≤ b ≤ +30° was obtained by photographic plates, taken at La Silla, Chile, with the super-wide-angle camera with spherical mirror of the Astronomisches Institut der Ruhr-Universität Bochum (Schmidt-Kaler et al. 1983). Schmidt-Kaler et al. (1983) and Seidensticker, Schmidt-Kaler, and Schlosser (1982) carried out an analysis of these plates. However, these studies used only a fraction of the whole plate; interesting parts of the sky were chosen near the plate centers, thus minimizing various errors. The plates are now all scanned over the whole field of view with a PDS with a diaphragm of 50 × 50 μm = 0.°12 × 0.° 12 on the sky. The image size is 1201 × 1201 pixels per plate. The mean deviation during the scan time was less than 0.1%. Through the identification of about 50 stars and by using their l, b and x, y coordinates, the equations of the plates were solved with eight geometric parameters. The standard deviation of all parameters was less than 0.3 pixels on all plates.
Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.
Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.
Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).
Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.
A new generation of solar instruments provides improved spectral, spatial, and temporal resolution, thus facilitating a better understanding of dynamic processes on the Sun. High-resolution observations often reveal multiple-component spectral line profiles, e.g., in the near-infrared He i 10830 Å triplet, which provides information about the chromospheric velocity and magnetic fine structure. We observed an emerging flux region, including two small pores and an arch filament system, on 2015 April 17 with the ‘very fast spectroscopic mode’ of the GREGOR Infrared Spectrograph (GRIS) situated at the 1.5-meter GREGOR solar telescope at Observatorio del Teide, Tenerife, Spain. We discuss this method of obtaining fast (one per minute) spectral scans of the solar surface and its potential to follow dynamic processes on the Sun. We demonstrate the performance of the ‘very fast spectroscopic mode’ by tracking chromospheric high-velocity features in the arch filament system.
Preterm birth and exposure to childhood sexual abuse (CSA) are early physiological and psychological adversities that have been linked to reduced social functioning across the lifespan. However, the joint effects of being born preterm and being exposed to CSA on adult social outcomes remains unclear. We sought to determine the impact of exposure to both preterm birth and CSA on adult social functioning in a group of 179 extremely low birth weight (ELBW; <1000 g) survivors and 145 matched normal birth weight (>2500 g) participants in the fourth decade of life. Social outcome data from a prospective, longitudinal, population-based Canadian birth cohort initiated between the years of 1977 and 1982 were examined. At age 29–36 years, ELBW survivors who experienced CSA reported poorer relationships with their partner, worse family functioning, greater loneliness, lower self-esteem and had higher rates of avoidant personality problems than those who had not experienced CSA. Birth weight status was also found to moderate associations between CSA and self-esteem (P=0.032), loneliness (P=0.021) and family functioning (P=0.060), such that the adverse effects of CSA were amplified in ELBW survivors. Exposure to CSA appears to augment the adult social risks associated with perinatal adversity. Individuals born preterm and exposed to CSA appear to be a group at particularly high risk for adverse social outcomes in adulthood.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
In general population samples, better childhood cognitive functioning is associated with decreased risk of depression in adulthood. However, this link has not been examined in extremely low birth weight survivors (ELBW, <1000 g), a group known to have poorer cognition and greater depression risk. This study assessed associations between cognition at age 8 and lifetime risk of major depressive disorder in 84 ELBW survivors and 90 normal birth weight (NBW, ⩾2500 g) individuals up to 29–36 years of age. The Wechsler Intelligence Scale for Children, Revised (WISC-R), Raven’s Coloured Progressive Matrices and the Token Test assessed general, fluid, and verbal intelligence, respectively, at 8 years of age. Lifetime major depressive disorder was assessed using the Mini International Neuropsychiatric Interview at age 29–36 years. Associations were examined using logistic regression adjusted for childhood socioeconomic status, educational attainment, age, sex, and marital status. Neither overall intelligence quotient (IQ) [WISC-R Full-Scale IQ, odds ratios (OR)=0.87, 95% confidence interval (CI)=0.43–1.77], fluid intelligence (WISC-R Performance IQ, OR=0.98, 95% CI=0.48–2.00), nor verbal intelligence (WISC-R Verbal IQ, OR=0.81, 95% CI=0.40–1.63) predicted lifetime major depression in ELBW survivors. However, every standard deviation increase in WISC-R Full-Scale IQ (OR=0.43, 95% CI=0.20–0.92) and Performance IQ (OR=0.46, 95% CI=0.21–0.97), and each one point increase on the Token Test (OR=0.80, 95% CI=0.67–0.94) at age 8 was associated with a reduced risk of lifetime depression in NBW participants. Higher childhood IQ, better fluid intelligence, and greater verbal comprehension in childhood predicted reduced depression risk in NBW adults. Our findings suggest that ELBW survivors may be less protected by superior cognition than NBW individuals.
This paper briefly describes the principle of operation and science goals of the AMANDA high energy neutrino telescope located at the South Pole, Antarctica. Results from an earlier phase of the telescope, called AMANDA-BIO, demonstrate both reliable operation and the broad astrophysical reach of this device, which includes searches for a variety of sources of ultrahigh energy neutrinos: generic point sources, Gamma-Ray Bursts and diffuse sources. The predicted sensitivity and angular resolution of the telescope were confirmed by studies of atmospheric muon and neutrino backgrounds. We also report on the status of the analysis from AMANDA-II, a larger version with far greater capabilities. At this stage of analysis, details of the ice properties and other systematic uncertainties of the AMANDA-II telescope are under study, but we have made progress toward critical science objectives. In particular, we present the first preliminary flux limits from AMANDA-II on the search for continuous emission from astrophysical point sources, and report on the search for correlated neutrino emission from Gamma Ray Bursts detected by BATSE before decommissioning in May 2000. During the next two years, we expect to exploit the full potential of AMANDA-II with the installation of a new data acquisition system that records full waveforms from the in-ice optical sensors.
Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered.
The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates.
Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis.
Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.
The present report is drastically shorter and, therefore, different in form from previous reports. While galactic research has increased considerably in recent years, the financial situation in the IAU made it necessary to reduce the size of the reports to half their previous size. This obliged us to adopt an almost telegraphic style in our report. However, an extended version of the report, including also the necessary references, will be published by the University of Thessaloniki and distributed to members of Commission 33. Any other interested astronomer may write to ask for a copy.
The report has been prepared by G. Contopoulos (Sections I, V, VI) and S. McCuskey (Sections II, III, IV). In our work we have been helped by Drs Kerr (radio astronomy) and Haradze (Russian contributions). Dr Elvius has written the Report of the Committee “Selected Areas”. We could cover the literature up to the fall of 1969, plus work in progress, reported by members of our commission.