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Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
Objective: Relative to the vast literature that employs measures of decision-making (DM), rigorous examination of their psychometric properties is sparse. This study aimed to determine whether three measures of DM assess the same construct, and to measure invariance of this construct across relevant covariates. Method: Participants were 372 adolescents at risk of escalation in cannabis use. DM was assessed via four indices from the Cups Task, Game of Dice Task (GDT), and Iowa Gambling Task (IGT). We used confirmatory factor analysis to assess unidimensionality of the DM construct, and moderated nonlinear factor analysis (MNLFA) to examine its measurement invariance. Results: The unidimensional model of DM demonstrated good fit. MNLFA results revealed that sex influenced mean DM scores, such that boys had lower risk-taking behaviors. There was evidence of differential item functioning (DIF), such that IQ and age moderated the IGT intercept and GDT factor loading, respectively. Significant effects were retained in the final model, which produced participant-specific DM factor scores. These scores showed moderate stability over time. Conclusions: Indices from three DM tasks loaded significantly onto a single factor, suggesting that these DM tasks assess a single underlying construct. We suggest that this construct represents the ability to make optimal choices that maximize rewards in the presence of risk. Our final DM factor accounts for DIF caused by covariates, making it comparable across adolescents with different characteristics. (JINS, 2019, 25, 661–667)
Filamentary structures can form within the beam of protons accelerated during the interaction of an intense laser pulse with an ultrathin foil target. Such behaviour is shown to be dependent upon the formation time of quasi-static magnetic field structures throughout the target volume and the extent of the rear surface proton expansion over the same period. This is observed via both numerical and experimental investigations. By controlling the intensity profile of the laser drive, via the use of two temporally separated pulses, both the initial rear surface proton expansion and magnetic field formation time can be varied, resulting in modification to the degree of filamentary structure present within the laser-driven proton beam.
Callous-unemotional (CU) traits are critical to developmental, diagnostic, and clinical models of antisocial behaviors (AB). However, assessments of CU traits within large-scale longitudinal and neurobiologically focused investigations remain remarkably sparse. We sought to develop a brief measure of CU traits using items from widely administered instruments that could be linked to neuroimaging, genetic, and environmental data within already existing datasets and future studies.
Data came from a large and diverse sample (n = 4525) of youth (ages~9–11) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study. Moderated nonlinear factor analysis was used to assess measurement invariance across sex, race, and age. We explored whether CU traits were distinct from other indicators of AB, investigated unique links with theoretically-relevant outcomes, and replicated findings in an independent sample.
The brief CU traits measure demonstrated strong psychometric properties and evidence of measurement invariance across sex, race, and age. On average, boys endorsed higher levels of CU traits than girls and CU traits were related to, yet distinguishable from other indicators of AB. The CU traits construct also exhibited expected associations with theoretically important outcomes. Study findings were also replicated across an independent sample of youth.
In a large, multi-site study, a brief measure of CU traits can be measured distinctly from other dimensions of AB. This measure provides the scientific community with a method to assess CU traits in the ABCD sample, as well as in other studies that may benefit from a brief assessment of CU.
Psychological risk factors that lead to impaired work performance, negatively impacting mental and physical health, have emerged as a concern across clinical settings. Although depression and anxiety are linked to poor physician mental health, physician burnout characterized by work related stress due to chronic exhaustion from clinical work, cynicism toward meaning of the medical profession, and feelings of inadequacy toward work related accomplishments, may be an even stronger indicator of well-being. Literature suggests that work satisfaction among physicians is rapidly deteriorating owing to high rates of burn out and poor mental health. Although the relationship between work burnout (WB) and negative affectivity has been well documented, the association with positive affect, such as trait forgiveness (TF) has been overlooked. On that note, research shows that lifetime stress severity and lower levels of forgiveness predict worse mental and physical health. Since TF has been linked strongly with healthy workplace relationships, positive occupational outcomes and general well-being, its association with WB remains to be investigated. Therefore, the aim of the present study was to explore the link between TF and WB among physicians. We hypothesized that TF would be associated with reduced levels of burnout.
A total of 62 (F=23) medical residents at a Teaching Hospital consented for the study. Residents were administered surveys on WB (Maslach BurnoutInventory), workplace bullying, personal bullying (PB), interpersonal rejection sensitivity (IRS), perceived stress scale (PSS), TF, anxiety, and depression, all of which were anonymously submitted via electronically. Hierarchical multiple regression (HMR) models were used to determine the associations between WB, work environment social factors and TF. A p-value of <0.05 was considered significant.
The mean age 33.1±SD 4.2 years. HMR analysis using WB as main outcome contained 6 predictors: Model 1 contained depression and anxiety, Model 2 added PB, Model 3 added IRS and PSS, Model 4 added TF. Anxiety and TF were the only significant predictors (p= >0.05) accounting for 10.4% and 17.5% of the variance in WB scores, respectively.
The novel finding of the present study is that TF was associated with low levels of burnout. Additionally, WB was found to be linked to anxiety and depression which is in line with previous research. These data suggest that TF could be a potential resolution to the deleterious influence of burnout. Further exploration is needed in order to understand the psychology of forgiveness as a potential adjuvant and/or therapeutic intervention for physicians’ burnout. These results suggest that strategies including forgiveness training aimed at decreasing WB while increasing job satisfaction among physicians warrant further exploration.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
To assess trends of mortality attributable to child and maternal undernutrition (CMU), overweight/obesity and dietary risks of non-communicable diseases (NCD) in sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD) Study 2015.
For each risk factor, a systematic review of data was used to compute the exposure level and the effect size. A Bayesian hierarchical meta-regression analysis was used to estimate the exposure level of the risk factors by age, sex, geography and year. The burden of all-cause mortality attributable to CMU, fourteen dietary risk factors (eight diets, five nutrients and fibre intake) and overweight/obesity was estimated.
All age groups and both sexes.
In 2015, CMU, overweight/obesity and dietary risks of NCD accounted for 826204 (95 % uncertainty interval (UI) 737346, 923789), 266768 (95 % UI 189051, 353096) and 558578 (95 % UI 453433, 680197) deaths, respectively, representing 10·3 % (95 % UI 9·1, 11·6 %), 3·3 % (95 % UI 2·4, 4·4 %) and 7·0 % (95 % UI 5·8, 8·3 %) of all-cause mortality. While the age-standardized proportion of all-cause mortality accounted for by CMU decreased by 55·2 % between 1990 and 2015 in SSA, it increased by 63·3 and 17·2 % for overweight/obesity and dietary risks of NCD, respectively.
The increasing burden of diet- and obesity-related diseases and the reduction of mortality attributable to CMU indicate that SSA is undergoing a rapid nutritional transition. To tackle the impact in SSA, interventions and international development agendas should also target dietary risks associated with NCD and overweight/obesity.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
Objectives: To examine neuropsychological test performance among individuals clinically diagnosed with Parkinson’s disease (PD) without evidence of dopaminergic deficiency on I-CIT single photon emission computed tomography imaging. Methods: Data were obtained from the Parkinson’s Progression Marker Initiative. The sample included 59 participants with scans without evidence of dopaminergic deficiency (SWEDD), 412 with PD, and 114 healthy controls (HC). Tests included Judgment of Line Orientation, Letter-Number Sequencing, Symbol Digit Modalities, Hopkins Verbal Learning Test-Revised, and Letter and Category Fluency. Multivariate analysis of variance was used to compare standardized scores between the groups. Results: There was a statistically significant difference in performances between the groups, F(14,1155)=5.04; p<.001; partial η2=.058. Pairwise comparisons revealed significant differences in Category Fluency between SWEDD (M=0.22; SD=1.08) and HC (M=0.86; SD=1.15) and in Symbol Digit Modalities Test performance between SWEDD (M=45.09; SD=11.54) and HC (M=51.75; SD=9.79). No significant differences between SWEDD and PD were found. Using established criteria, approximately one in four participants in the SWEDD and PD groups met criteria for mild cognitive impairment (MCI). Conclusions: Individuals with SWEDD demonstrate significantly worse mental processing speed and semantic fluency than HC. The neuropsychological test performances and rates of MCI were similar between the SWEDD group and PD groups, which may reflect a common pathology outside of the nigrostriatal pathway. (JINS, 2018, 24, 646–651)
This study investigates relations of maternal N-3 and N-6 polyunsaturated fatty acids (PUFA) intake during pregnancy with offspring body mass index (BMI), height z-score and metabolic risk (fasting glucose, C-peptide, leptin, lipid profile) during peripuberty (8–14 years) among 236 mother–child pairs in Mexico. We used food frequency questionnaire data to quantify trimester-specific intake of N-3 alpha-linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); N-6 linoleic acid and arachidonic acid (AA); and N-6:N-3 (AA:EPA+DHA), which accounts for the fact that the two PUFA families have opposing effects on physiology. Next, we used multivariable linear regression models that accounted for maternal education and parity, and child’s age, sex and pubertal status, to examine associations of PUFA intake with the offspring outcomes. In models where BMI z-score was the outcome, we also adjusted for height z-score. We found that higher second trimester intake of EPA, DHA and AA were associated with lower offspring BMI and height z-score. For example, each 1-s.d. increment in second trimester EPA intake corresponded with 0.25 (95% CI: 0.03, 0.47) z-scores lower BMI and 0.20 (0.05, 0.36) z-scores lower height. Accounting for height z-score in models where BMI z-score was the outcome attenuated estimates [e.g., EPA: −0.16 (−0.37, 0.05)], suggesting that this relationship was driven by slower linear growth rather than excess adiposity. Maternal PUFA intake was not associated with the offspring metabolic biomarkers. Our findings suggest that higher PUFA intake during mid-pregnancy is associated with lower attained height in offspring during peripuberty. Additional research is needed to elucidate mechanisms and to confirm findings in other populations.
A far-infrared observatory such as the SPace Infrared telescope for Cosmology and Astrophysics, with its unprecedented spectroscopic sensitivity, would unveil the role of feedback in galaxy evolution during the last ~10 Gyr of the Universe (z = 1.5–2), through the use of far- and mid-infrared molecular and ionic fine structure lines that trace outflowing and infalling gas. Outflowing gas is identified in the far-infrared through P-Cygni line shapes and absorption blueshifted wings in molecular lines with high dipolar moments, and through emission line wings of fine-structure lines of ionised gas. We quantify the detectability of galaxy-scale massive molecular and ionised outflows as a function of redshift in AGN-dominated, starburst-dominated, and main-sequence galaxies, explore the detectability of metal-rich inflows in the local Universe, and describe the most significant synergies with other current and future observatories that will measure feedback in galaxies via complementary tracers at other wavelengths.
Habitat preferences and response to habitat conversion remain under-studied for many groups in the tropics, limiting our understanding of how environmental and anthropogenic factors may interact to shape patterns of diversity. To help fill this knowledge gap, we surveyed nocturnal birds such as owls, nightjars and potoos through auditory transect surveys in 22 forest fragments (2.7 to 33.6 ha) in north-west Ecuador. We assessed the relative effect of habitat characteristics (e.g. canopy height and openness, and density of large trees) and fragment attributes (e.g. area, altitude and proportion of surrounding forest cover) on species richness and community composition. Based on our previous work, we predicted that nocturnal bird richness would be highest in relatively larger fragments with more surrounding forest cover. We recorded 11 total species with an average ± SD of 3.4 ± 1.4 (range = 2–7) species per fragment, with higher richness in fragments that were larger, at lower altitudes, and characterized by more open canopies. Nocturnal bird community similarity was not significantly correlated with any measured environmental variable. These results indicate that both landscape (e.g. altitude) and fragment-specific (e.g. size, forest structure) attributes are likely to interact to shape patterns of diversity among this poorly known but ecologically important guild in fragmented tropical landscapes.
Cannabis use has been linked to impairments in neuropsychological functioning across a large and continually expanding body of research. Yet insight into underlying causal relations remains limited due to the historically cross-sectional nature of studies in this area. Recently, however, studies have begun to use more informative design strategies to delineate these associations. The aim of this article is to provide a critical evaluation and review of research that uses longitudinal designs to examine the link between cannabis use and neuropsychological functioning. In summarizing the primary findings across these studies, this review suggests that cannabis use leads to neuropsychological decline. However, across most studies, these associations were modest, were present only for the group with the heaviest cannabis use, and were often attenuated (or no longer significant) after controlling for potential confounding variables. Future studies with neuropsychological data before and after initiation of cannabis use, along with careful measurement and control of “shared risk factors” between cannabis use and poorer neuropsychological outcomes, are needed to better understand who, and under what conditions, is most vulnerable to cannabis-associated neuropsychological decline. (JINS, 2017, 23, 893–902)
With 30 threatened species (14 categorized as Critically Endangered and 16 as Endangered, sensu IUCN), Coccothrinax (c. 54 species) is the flagship palm genus for conservation in the Caribbean Island Biodiversity Hotspot. Coccothrinax has its centre of taxonomic diversity in these islands, with c. 51 endemic species. We present a conservation framework for the 14 Critically Endangered species, found in Cuba, Haiti or the Dominican Republic. Only two species (C. jimenezii, C. montana) occur in more than one country (Haiti and the Dominican Republic). Immediate threats include oil drilling and nickel mining, intrusion of saline water into soil, urban and agricultural development, low population recruitment, uncontrolled fires, interspecific hybridization, and unsustainable ethnobotanical practices. Coccothrinax bermudezii, C. borhidiana, C. crinita ssp. crinita, C. leonis and C. spissa are not conserved in protected areas. Coccothrinax bermudezii, C. jimenezii, C. leonis and C. nipensis are not part of ex situ collections. Based on results from a conservation project targeting C. jimenezii, we recommend international cooperation between the three range states to implement integrative conservation management plans, plant exploration initiatives, taxonomic revisions, outreach, and fundraising. The ultimate aim of this review is to provide baseline information that will develop conservation synergy among relevant parties working on Coccothrinax conservation in Cuba, Haiti and the Dominican Republic. Such collaborations could also benefit through partnerships with botanists working in other countries.
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.
Extreme solar-terrestrial events are those in which very energetic solar ejections hit the earth?s magnetosphere, causing intense energization of the earth?s ring current. Statistically, their occurrence is approximately once per Gleissberg solar cycle (70-100yrs). The solar transient occurred on July, 23rd (2012) was potentially one of such extreme events. The associated coronal mass ejection (CME), however, was not ejected towards the earth. Instead, it hit the STEREO A spacecraft, located 120 degrees away from the Sun-Earth line. Estimates of the geoeffectiveness of such a CME point to a scenario of extreme Space Weather conditions. In terms of the ring current energization, as measured by the Disturbance Storm-Time index (Dst), had this CME hit the Earth, it would have caused the strongest geomagnetic storm in space era.
Blazar OJ 287 is one of the best observed extragalactic objects. It's historical light curve goes back to 1890′s. Based on the historical behaviour Sillanpää et al. (1988) showed that OJ 287 displays large periodic outbursts, with a period of 11.7 years. We have monitored OJ 287 intensively for two years, during the OJ-94 project. This project was created for monitoring OJ 287 during its predicted new outburst in 1994. In the data archive we have over 7000 observations on OJ 287, in the radio, infrared and optical bands. This data archive contains the best ever obtained light curves for any extragalactic object. The optical light curve shows continuous variability down to time scales of tens of minutes. The variability observed in OJ 287 can be broken down to (at least) four different categories:
Energy reserve, estimated as body condition score (BCS), is the major determinant of the re-initiation of ovarian activity in postpartum cows. Leptin, IGF-I and insulin are positively related to BCS and are putative mediators between BCS and reproductive function. However, when BCS and body composition dissociates, concentrations of these metabolic hormones are altered. We hypothesized that increasing lean muscle tissue, but not fat tissue, would diminish the reproductive response to oestrus induction treatments. Thirty lactating beef cows with BCS of 3.10±1.21 and 75.94±12 days postpartum were divided in two groups. Control cows (n=15) were supplemented with 10.20 kg of concentrate daily for 60 days. Treated cows (n=15) were supplemented equally, and received a β-adrenergic receptor agonist (β-AA; 0.15 mg/kg BW) to achieve accretion of lean tissue mass and not fat tissue mass. Twelve days after ending concentrate supplementation/β-AA treatment, cows received a progestin implant to induce oestrus. Cows displaying oestrus were inseminated during the following 60 days, and maintained with a fertile bull for a further 21 days. Cows in both groups gained weight during the supplementation period (Daily weight gain: Control=0.75 kg v. β-AA=0.89 kg). Cows treated with β-AA had a larger increase in BCS (i.e. change in BCS: control=1 point (score 4.13) v. β-AA=2 points (score 5.06; P<0.05), as a result of muscle accretion (i.e. change in muscle depth: control 0.21 cm v. β-AA 0.97 cm; P<0.05) but not adipose tissue (i.e. change in back fat depth; control 0.13 cm v. β-AA −0.06 cm; P<0.05). The changes in body composition in β-AA cows were associated with a reduction in serum concentrations of IGF-I (25.4%) and leptin (27.9%), without observed changes in insulin. Ovulation and pregnancy to 1st service (P>0.05) did not differ between groups. However, the number of cows displaying oestrus (control 13/15 v. β-AA 8/15; P<0.05) and the percentage cycling (control 6/8 v. β-AA 3/10; P=0.07) after progestin treatment and the pregnancy percentage at the end of the breeding period (control 13/15 v. β-AA 8/15; P<0.05) were lower in β-AA than control cows. In summary, the increase BCS through muscle tissue accretion, but not through fat tissue accretion, resulted in a lower response to oestrus induction, lower percentage of cycling animals and lower pregnancy percentage after progestin treatment; which was associated with a decrease in serum concentrations of leptin and IGF-I.
On May 22, 1989 the Japanese Ginga Team discovered a new X-ray source that was cataloged as GS 2023+338. This source was subsequently identified as coincident in position with a previously known nova cataloged as V404 Cygni. Its last recorded outburst was in 1938 when it rose to about 12th mag. Spectroscopic data were obtained and confirmed the nature of the outburst. Additional ground based data were obtained by us at CTIO and the VLA. The X-ray behavior of this object has been reported to be very unusual and it reached a peak of about 17 crab about one week after discovery. Since then it has varied widely in magnitude at all wavelengths at which it has been studied. We present a brief summary of the observations that have been obtained up to the time of the meeting and shortly thereafter.