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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.
Fatigue syndromes (FSs) affect large numbers of individuals, yet evidence from epidemiological studies on adverse outcomes, such as premature death, is limited.
Cohort study involving 385 general practices in England that contributed to the Clinical Practice Research Datalink (CPRD) with linked inpatient Hospital Episode Statistics (HES) and Office for National Statistics (ONS) cause of death information. A total of 10 477 patients aged 15 years and above, diagnosed with a FS during 2000–2014, were individually matched with up to 20 comparator patients without a history of having a FS. Prevalence ratios (PRs) were estimated to compare the FS and comparison cohorts on clinical characteristics. Adjusted hazard ratios (HRs) for subsequent adverse outcomes were estimated from stratified Cox regression models.
Among patients diagnosed with FSs, we found elevated baseline prevalence of: any psychiatric illness (PR 1.77; 95% CI 1.72–1.82), anxiety disorders (PR 1.92; 1.85–1.99), depression (PR 1.89; 1.83–1.96), psychotropic prescriptions (PR 1.68; 1.64–1.72) and comorbid physical illness (PR 1.28; 1.23–1.32). We found no significant differences in risks for: all-cause mortality (HR 0.99; 0.91–1.09), natural death (HR 0.99; 0.90–1.09), unnatural death (HR 1.00; 0.59–1.72) or suicide (HR 1.68; 0.78–3.63). We did, however, observe a significantly elevated non-fatal self-harm risk: HR 1.83; 1.56–2.15.
The absence of elevated premature mortality risk is reassuring. The raised prevalence of mental illness and increased non-fatal self-harm risk indicate a need for enhanced assessment and management of psychopathology associated with fatigue syndromes.
Introduction: Identification of latent safety threats (LSTs) in the emergency department is an important aspect of quality improvement that can lead to improved patient care. In situ simulation (ISS) takes place in the real clinical environment and multidisciplinary teams can participate in diverse high acuity scenarios to identify LSTs. The purpose of this study is to examine the influence that the profession of the participant (i.e. physician, registered nurse, or respiratory therapist) has on the identification of LSTs during ISS. Methods: Six resuscitation- based adult and pediatric simulated scenarios were developed and delivered to multidisciplinary teams in the Kingston General Hospital ED. Each ISS session consisted of a 10- minute scenario, followed by 3-minutes of individual survey completion and a 7- minute group debrief led by ISS facilitators. An objective assessor recorded LSTs identified during each debrief. Surveys were completed prior to debrief to reduce response bias. Data was collected on participant demographics and perceived LSTs classified in the following categories: medication; equipment; resources and staffing; teamwork and communication; or other. Two reviewers evaluated survey responses and debrief notes to formulate a list of unique LSTs across scenarios and professions. The overall number and type of LSTs from surveys was identified and stratified by health care provider. Results: Thirteen ISS sessions were conducted with a total of 59 participants. Thirty- four unique LSTs (8 medication, 15 equipment, 5 resource, 4 communication, and 2 miscellaneous issues) were identified from surveys and debrief notes. Overall, MDs (n = 12) reported 19 LSTss (n = 41) reported 77 LSTs, and RTs (n = 6) reported 4 LSTs based on individual survey data. The most commonly identified category of LSTs reported by MDs (36.8%) and RTs (75%) was equipment issues while RNs most commonly identified medication issues (36.4%). Participants with □5 years of experience in their profession, on average identified more LSTs in surveys than participants with >5 years experience (1.9 LSTs vs 1.5 LSTs respectively). Conclusion: Nursing staff identified the highest number of LSTs across all categories. There was fairly unanimous identification of major LSTs across professions, however each profession did identify unique perspectives on LSTs in survey responses. ISS programs with the purpose of LST identification would benefit from multidisciplinary participation.
A 2018 workshop on the White Mountain Apache Tribe lands in Arizona examined ways to enhance investigations into cultural property crime (CPC) through applications of rapidly evolving methods from archaeological science. CPC (also looting, graverobbing) refers to unauthorized damage, removal, or trafficking in materials possessing blends of communal, aesthetic, and scientific values. The Fort Apache workshop integrated four generally partitioned domains of CPC expertise: (1) theories of perpetrators’ motivations and methods; (2) recommended practice in sustaining public and community opposition to CPC; (3) tactics and strategies for documenting, investigating, and prosecuting CPC; and (4) forensic sedimentology—uses of biophysical sciences to link sediments from implicated persons and objects to crime scenes. Forensic sedimentology served as the touchstone for dialogues among experts in criminology, archaeological sciences, law enforcement, and heritage stewardship. Field visits to CPC crime scenes and workshop deliberations identified pathways toward integrating CPC theory and practice with forensic sedimentology’s potent battery of analytic methods.
The Commensal Real-time Australian Square Kilometre Array Pathfinder Fast Transients survey is the first extensive astronomical survey using phased array feeds. Since January 2017, it has been searching for fast radio bursts in fly’s eye mode. Here, we present a calculation of the sensitivity and total exposure of the survey that detected the first 20 of these bursts, using the pulsars B1641-45 and B0833-45 as calibrators. The beamshape, antenna-dependent system noise, and the effects of radio-frequency interference and fluctuations during commissioning are quantified. Effective survey exposures and sensitivities are calculated as a function of the source counts distribution. Statistical ‘stat’ and systematics ‘sys’ effects are treated separately. The implied fast radio burst rate is significantly lower than the 37 sky−1 day−1 calculated using nominal exposures and sensitivities for this same sample by Shannon et al. (2018). At the Euclidean (best-fit) power-law index of −1.5 (−2.2), the rate is
(sys) ± 3.6 (stat) sky−1 day−1 (
(sys) ± 2.8 (stat) sky−1 day−1) above a threshold of 56.6 ± 6.6(sys) Jy ms (40.4 ± 1.2(sys) Jy ms). This strongly suggests that these calculations be performed for other FRB-hunting experiments, allowing meaningful comparisons to be made between them.
The GaLactic and Extragalactic All-sky Murchison Widefield Array survey is a radio continuum survey at 72–231 MHz of the whole sky south of declination +30º, carried out with the Murchison Widefield Array. In this paper, we derive source counts from the GaLactic and Extragalactic All-sky Murchison data at 200, 154, 118, and 88 MHz, to a flux density limit of 50, 80, 120, and 290 mJy respectively, correcting for ionospheric smearing, incompleteness and source blending. These counts are more accurate than other counts in the literature at similar frequencies as a result of the large area of sky covered and this survey’s sensitivity to extended emission missed by other surveys. At S154 MHz > 0.5 Jy, there is no evidence of flattening in the average spectral index (α ≈ −0.8 where S ∝ vα) towards the lower frequencies. We demonstrate that the Square Kilometre Array Design Study model by Wilman et al. significantly underpredicts the observed 154-MHz GaLactic and Extragalactic All-sky Murchison counts, particularly at the bright end. Using deeper Low-Frequency Array counts and the Square Kilometre Array Design Study model, we find that sidelobe confusion dominates the thermal noise and classical confusion at v ≳ 100 MHz due to both the limited CLEANing depth and the undeconvolved sources outside the field-of-view. We show that we can approach the theoretical noise limit using a more efficient and automated CLEAN algorithm.
In the past few years, there has been an unprecedented increase in the number of forcibly displaced migrants worldwide, of which a substantial proportion is refugees and asylum seekers. Refugees and asylum seekers may experience high levels of psychological distress, and show high rates of mental health conditions. It is therefore timely and particularly relevant to assess whether current evidence supports the provision of psychosocial interventions for this population. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the efficacy and acceptability of psychosocial interventions compared with control conditions (treatment as usual/no treatment, waiting list, psychological placebo) aimed at reducing mental health problems in distressed refugees and asylum seekers.
We used Cochrane procedures for conducting a systematic review and meta-analysis of RCTs. We searched for published and unpublished RCTs assessing the efficacy and acceptability of psychosocial interventions in adults and children asylum seekers and refugees with psychological distress. Post-traumatic stress disorder (PTSD), depressive and anxiety symptoms at post-intervention were the primary outcomes. Secondary outcomes include: PTSD, depressive and anxiety symptoms at follow-up, functioning, quality of life and dropouts due to any reason.
We included 26 studies with 1959 participants. Meta-analysis of RCTs revealed that psychosocial interventions have a clinically significant beneficial effect on PTSD (standardised mean difference [SMD] = −0.71; 95% confidence interval [CI] −1.01 to −0.41; I2 = 83%; 95% CI 78–88; 20 studies, 1370 participants; moderate quality evidence), depression (SMD = −1.02; 95% CI −1.52 to −0.51; I2 = 89%; 95% CI 82–93; 12 studies, 844 participants; moderate quality evidence) and anxiety outcomes (SMD = −1.05; 95% CI −1.55 to −0.56; I2 = 87%; 95% CI 79–92; 11 studies, 815 participants; moderate quality evidence). This beneficial effect was maintained at 1 month or longer follow-up, which is extremely important for populations exposed to ongoing post-migration stressors. For the other secondary outcomes, we identified a non-significant trend in favour of psychosocial interventions. Most evidence supported interventions based on cognitive behavioural therapies with a trauma-focused component. Limitations of this review include the limited number of studies collected, with a relatively low total number of participants, and the limited available data for positive outcomes like functioning and quality of life.
Considering the epidemiological relevance of psychological distress and mental health conditions in refugees and asylum seekers, and in view of the existing data on the effectiveness of psychosocial interventions, these interventions should be routinely made available as part of the health care of distressed refugees and asylum seekers. Evidence-based guidelines and implementation packages should be developed accordingly.
Globally, the prevalence of tuberculosis (TB) disease is higher in males. This study examined the effect of sex and age on Mycobacterium tuberculosis (Mtb) infection. Demographic and exposure data were collected on household contacts of sputum smear-positive pulmonary TB patients in Brazil. Contacts with tuberculin skin test induration ⩾10 mm at baseline or 12 weeks were considered Mtb infected. The study enrolled 917 household contacts from 160 households; 508 (55.4%) were female, median age was 21.0 years (range 0.30–87.0) and 609 (66.4%) had Mtb infection. The proportion infected increased with age from 63.3% in girls <5 years to 75.4% in women ⩾40 years and from 44.9% in boys <5 years to 73.6% in men ⩾40 years. Multivariable modelling showed the odds of infection increased between age 5 and 14 years among female contacts (OR 1.5 per 5-year age increase; 95% CI 1.1–2.2; P = 0.02) and between ages 0–4 and 15–39 years among male contacts (OR 2.7, 95% CI 0.83–8.9 and 1.1, 95% CI 0.99–1.3 per 5-year age increase; P = 0.10, 0.07, respectively). The study suggests that the age at which Mtb infection increases most is different in females compared with males. Studies are needed to explore whether these findings are due to differences in host susceptibility, exposure outside the household or other factors.
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.
Housed pigs are exposed chronically to aerial pollutants, principally dust and ammonia, at concentrations that may affect performance, possibly by raising the incidence and prevalence of multi-factorial respiratory diseases. Tolerable limits for aerial pollutants are unknown. The aim of this experiment was to test the hypothesis that chronic exposure of weaner pigs to controlled concentrations of aerial dust and ammonia lead to slower growth and lower feed intake compared with controls kept in ‘fresh air’.
The purpose of an integrated management system is to optimise both pig performance and environmental protection. A major impediment to this process has been the inability to measure and control the production process in real time, for specific and contemporary pig batches. Optimisation thus requires in-line measurement of pig growth performance, together with the means to change performance with adjustments to feed quantity and quality. This report deals with the use of visual image analysis (VIA) to provide the first of these; measurement of growth. VIA determines, continuously and in-line, the size and shape of the plan view of the pig as it stands at the feeder. Three seminal questions are here addressed. (i) can VIA be used to provide a reliable measure of pig weight, and (ii) how many days are required to elapse before a change in size can be reliably determined and how does the VIA system compare with daily weighing by a conventional weigh-scale, and (iii) can VIA sort pigs according to their shape?
Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome.
We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups.
The most statistically significant and clinically recognizable model comprised five subgroups. The largest, ‘core’ subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms – a group which combined features of both of the above (14%). The smallest ‘avoidant–inactive’ subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups.
In addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
Very preterm birth (VPT; <32 weeks of gestation) has been associated with impairments in emotion regulation, social competence and communicative skills. However, the neuroanatomical mechanisms underlying such impairments have not been systematically studied. Here we investigated the functional integrity of the amygdala connectivity network in relation to the ability to recognize emotions from facial expressions in VPT adults.
Thirty-six VPT-born adults and 38 age-matched controls were scanned at rest in a 3-T MRI scanner. Resting-state functional connectivity (rs-fc) was assessed with SPM8. A seed-based analysis focusing on three amygdalar subregions (centro-medial/latero-basal/superficial) was performed. Participants’ ability to recognize emotions was assessed using dynamic stimuli of human faces expressing six emotions at different intensities with the Emotion Recognition Task (ERT).
VPT individuals compared to controls showed reduced rs-fc between the superficial subregion of the left amygdala, and the right posterior cingulate cortex (p = 0.017) and the left precuneus (p = 0.002). The VPT group further showed elevated rs-fc between the left superficial amygdala and the superior temporal sulcus (p = 0.008). Performance on the ERT showed that the VPT group was less able than controls to recognize anger at low levels of intensity. Anger scores were significantly associated with rs-fc between the superficial amygdala and the posterior cingulate cortex in controls but not in VPT individuals.
These findings suggest that alterations in rs-fc between the amygdala, parietal and temporal cortices could represent the mechanism linking VPT birth and deficits in emotion processing.
In the two years since the first successful measurements of 14C by high energy mass spectrometry, the advantages and the basic techniques of the method have been sufficiently reported. They will not be repeated here. This paper describes the work being done at Oxford to fill the gap between demonstrating the effectiveness of the approach and the creation of a facility dedicated to the carbon dating of milligram samples.
We present preliminary results of grating observations of YY Mensae and V824 Arae by Chandra and XMM-Newton. Spectral features are presented in the context of the emission measure distributions, the coronal abundances, and plasma electron densities. In particular, we observe a coronal N/C enhancement in YY Men believed to reflect the photospheric composition (CN cycle). Finally, we interpret line broadening in YY Men as Doppler thermal broadening in its very hot corona.
We have undertaken an adaptive optics imaging survey of extra-solar planetary systems and stars showing interesting radial velocity trends from high precision radial velocity searches. Adaptive Optics increases the resolution and dynamic range of an image, substantially improving the detectability of faint close companions. This survey is sensitive to objects less luminous than the bottom of the main sequence at separations as close as 1″. We have detected stellar companions to the planet bearing stars HD 114762 and Tau Boo. We have also detected a companion to the non-planet bearing star 16 Cyg A.
GRS1915+105 is an extraordinary X-ray transient which exhibits superluminal radio jets. In this paper, ASCA observations of the GRS1915+105 conducted from 1994 to 1997 are reported. Observations are carried out on the following dates each for ~ 20 ksec exposure; Sep 27 1994, April 20 1995, Oct 23 1996 and Apr 25 1997.