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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.
Hypertension prevalence is on the rise in low- and middle-income countries (LMICs) like South Africa, and migration and its concomitant urbanization are often considered to be associated with this rise. However, relatively little is known about the relationship between blood pressure (BP) and internal migration – a highly prevalent population process in LMICs. This study employed data for a group of 194 adult men and women from an original pilot dataset drawn from the Agincourt Health and Demographic Surveillance System in north-east South Africa conducted in 2012. Migrants in the sample were identified, tracked and interviewed. The relationship between BP and migration distance and the number of months an individual spent away from his/her home village was estimated using robust OLS regression, controlling for a series of socioeconomic, health and behavioural characteristics. It was found that migrants who moved a longer distance and for longer durations had significantly higher systolic and diastolic blood pressures compared with shorter-term migrants and those who remained nearby or in their home village. These associations remained robust and statistically significant when adjusting for measures of socioeconomic conditions, as well as body mass index and the number of meals consumed per day. Migration, both in terms of distance and time away, explained significant variation in the blood pressure of migrants in this typical South African context. The findings suggest the need for further studies of the nutritional and psycho-social factors associated with geographic mobility that may be important to understand rising hypertension levels in LMICs.
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.
Apatite-type materials AI4AII6(BO4)6X2 have two unique cations sites AI and AII, which can host large mono-, di- tri- and tetra-valent cations. The average cation radii will affect the twist angle and lattice constants. However, there are few reports on the influence of B site substitutions on the twist angle and lattice parameters. It is believed that the lattice constant variation as a function of B site substitutions may not follow the same twist-angle model as proposed for A site. This work reports our results on the crystal chemistry of synthetic apatite Ca10(VxP1−xO4)6F2 obtained through the crystal structure characterization using Rietveld refinement and high-resolution transmission electron microscopy. The quantification of vanadium/phosphorus partitioning in BO4 tetrahedra showed that equilibrium with more than 70% substitution of phosphorous by vanadium was difficult to achieve unless longer annealing (about 1 week at 900 °C) was employed. In comparison with the apatites with different ionic radii at AI and AII sites, Ca10(VxP1−xO4)6F2 apatites with different ionic radii at B site show little twist angle variation for the whole series, which indicates that the dilation of unit cell constants is mainly because of the expansions of BO4 tetrahedra when A site cation is fixed.
A novel method has been investigated for the study of extended X-ray absorption-edge fine structures. The method takes advantage of the absorption of continuum X-rays that emerge at low takeoff angles from an electron-bombarded target. The extended fine structure is observed as undulations in the continuum X-ray intensity in the region of the self-absorption edge. Spectra from conventional X-ray diffraction tubes have been recorded for various values of kilovolts and takeoff angles. Spectra obtained by this method are compared with published data. Nearly all the features of the extended fine structures can be clearly resolved by this technique. In the case of iron ar.d copper targets, it is found, experimentally that the best contrast is obtained when using a 50-kV accelerating voltage. A takeoff angle of 3° yielded best results for copper, while an angle of 10° was best suited for iron. The Philibert absorption correction successfully used in electron microprobe analysis has been extended to account for the observed self-absorption effect where κΔλ = f(x)λ1/f(x)λ2. The primary advantage of the thick-target technique is in the ability to obtain absorption spectra without having to prepare thin films. The technique is essentially nondestructive in that the sample need not be pulverized or thinned.
Over the past 25 years, numerous studies utilizing both X-ray diffraction (XRE) and differential scanning calorimetry (DSC) have been reported In the literature. Generally, conventional high-temperature X-ray data identifies solid-state transitions, then attempts to correlate them with thermal events observed by the calorimeter. Since changes occur in the sample during studies such as these, separate portions of the sample must be used for XRD and DSC experiments. When comparing results of the two experiments, questions arise concerning sample homogeniety as well as temperature and environmental differences. In fact, no conventional high-temperature X-ray diffraction instrument can give the precise control over temperature and heating rate available with a DSC, The problems of sample inhomogeneltles and Instrumental differences could be avoided if X-ray diffraction and DSC could be performed simultaneously on one sample.
Due to the difficulty of analyzing materials at high temperatures and in reactive atmospheres, solid-state catalysts have often been developed with little knowledge of the true chemical behavior of the catalyst, except on a bulk scale. In the field of solid-state catalysis research, a great deal of time and effort is presently being spent to better characterize the chemical and physical properties which determine a particular catalyst‘s efficiency, lifetime, and selectivity. Recently, we have undertaken a study of model copper catalysts at The Dow Chemical Company in an effort to better understand the chemical and physical properties which determine the efficiency, regenerability, and lifetime of this type of solid state catalyst.
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.
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.
Magnetic field measurements in turbulent plasmas are often difficult to perform. Here we show that for
kG magnetic fields, a time-resolved Faraday rotation measurement can be made at the OMEGA laser facility. This diagnostic has been implemented using the Thomson scattering probe beam and the resultant path-integrated magnetic field has been compared with that of proton radiography. Accurate measurement of magnetic fields is essential for satisfying the scientific goals of many current laser–plasma experiments.
To examine perspectives on food access among low-income families participating in a cost-offset community-supported agriculture (CO-CSA) programme.
Farm Fresh Foods for Healthy Kids (F3HK) is a multicentre randomized intervention trial assessing the effect of CO-CSA on dietary intake and quality among children from low-income families. Focus groups were conducted at the end of the first CO-CSA season. Participants were interviewed about programme experiences, framed by five dimensions of food access: availability, accessibility, affordability, acceptability and accommodation. Transcribed data were coded on these dimensions plus emergent themes.
Nine communities in the US states of New York, North Carolina, Washington and Vermont.
Fifty-three F3HK adults with children.
CSA models were structured by partner farms. Produce quantity was abundant; however, availability was enhanced for participants who were able to select their own produce items. Flexible CSA pick-up times and locations made produce pick-up more accessible. Despite being affordable to most, payment timing was a barrier for some. Unfamiliar foods and quick spoilage hindered acceptability through challenging meal planning, despite accommodations that included preparation advice.
Although CO-CSA may facilitate increased access to fruits and vegetables for low-income families, perceptions of positive diet change may be limited by the ability to incorporate share pick-up into regular travel patterns and meal planning. Food waste concerns may be particularly acute for families with constrained resources. Future research should examine whether CO-CSA with flexible logistics and produce self-selection are sustainable for low-income families and CSA farms.
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?
Grassland silage management is generally ad hoc resulting in soil compaction damage. Literature suggests grass yield reductions of 5 to 74% through compaction (UK mean 13%), while a 2015 study, reported here, comparing grass dry matter (DM) yield between controlled traffic farming (CTF) and normal management (N), found a 13.5% (0.80 t ha−1) increase for CTF. Commercially available grass forage equipment with widths of 3 to 12 m set up for CTF reduced trafficked areas from 80%–90% for N to 40%–13%. Economic analysis based on 13% increase in DM for 2 and 3 cut systems, gave an increased grass value between £38 ha−1 and £98 ha−1. CTF for multi-cut grass silage effectively increases yields by reducing compaction and sward damage.