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Pharmacokinetically important polymorphisms could guide dosing, ensuring adequate CNS bioavailability in a particular individual during a therapeutic trial. Hepatic enzyme (CYP450) polymorphisms have been extensively studied. Less work has been done on the permeability glycoprotein (P-gp) - the key efflux pump at the blood brain barrier (BBB).
An eight week prospective multi-centre candidate gene association study of 113 patients with psychiatrist diagnosed DSM-IV MDD was conducted. Subjects were treated with escitalopram (ESCIT) or venlafaxine (VEN) in a naturalistic clinical setting. Treatment outcome was assessed with the 17-item HDRS and Clinical Global Impression (CGI) Scales. Side effects were rated with a comprehensive adverse reactions scale (UKU). All response ratings were blinded to genotype. P-gp, CYP2D6, and CYP2C19 polymorphisms were assayed using microarray methodology.
BBB (P-gp) polymorphisms associated with less antidepressant CNS entry were associated with need for higher medication dosage and less overall clinical improvement. Patients with higher BBB block polymorphism need 1.45 (p = 0.018) times the dose of escitalopram than those with lower blood brain barrier block polymorphism. Patients with lower BBB block genotype had a 1.602 time greater reduction in depression compared to subjects with higher block polymorphisms (p = 0.043). Subjects with lower BBB block and poorer metaboliser status at cytochrome P450 2D6 and 2C19 genotype were significantly more likely to respond on the HDRS (RR = 1.60, 95%CI 1.095–2.339, p = 0.015).
This is the first study to demonstrated that P-gp polymorphisms predict antidepressant dose, and that combined P450 and P-gp polymorphisms predict antidepressant response.
We compared systematic and random survey techniques to estimate breeding population sizes of burrow-nesting petrel species on Marion Island. White-chinned (Procellaria aequinoctialis) and blue (Halobaena caerulea) petrel population sizes were estimated in systematic surveys (which attempt to count every colony) in 2009 and 2012, respectively. In 2015, we counted burrows of white-chinned, blue and great-winged (Pterodroma macroptera) petrels within 52 randomized strip transects (25 m wide, total 144 km). Burrow densities were extrapolated by Geographic Information System-derived habitat attributes (geology, vegetation, slope, elevation, aspect) to generate island-wide burrow estimates. Great-winged petrel burrows were found singly or in small groups at low densities (2 burrows ha−1); white-chinned petrel burrows were in loose clusters at moderate densities (3 burrows ha−1); and blue petrel burrows were in tight clusters at high densities (13 burrows ha−1). The random survey estimated 58% more white-chinned petrels but 42% fewer blue petrels than the systematic surveys. The results suggest that random transects are best suited for species that are widely distributed at low densities, but become increasingly poor for estimating population sizes of species with clustered distributions. Repeated fixed transects provide a robust way to monitor changes in colony density and area, but might fail to detect the formation/disappearance of new colonies.
Feed represents a substantial proportion of production costs in the dairy industry and is a useful target for improving overall system efficiency and sustainability. The objective of this study was to develop methodology to estimate the economic value for a feed efficiency trait and the associated methane production relevant to Canada. The approach quantifies the level of economic savings achieved by selecting animals that convert consumed feed into product while minimizing the feed energy used for inefficient metabolism, maintenance and digestion. We define a selection criterion trait called Feed Performance (FP) as a 1 kg increase in more efficiently used feed in a first parity lactating cow. The impact of a change in this trait on the total lifetime value of more efficiently used feed via correlated selection responses in other life stages is then quantified. The resulting improved conversion of feed was also applied to determine the resulting reduction in output of emissions (and their relative value based on a national emissions value) under an assumption of constant methane yield, where methane yield is defined as kg methane/kg dry matter intake (DMI). Overall, increasing the FP estimated breeding value by one unit (i.e. 1 kg of more efficiently converted DMI during the cow’s first lactation) translates to a total lifetime saving of 3.23 kg in DMI and 0.055 kg in methane with the economic values of CAD $0.82 and CAD $0.07, respectively. Therefore, the estimated total economic value for FP is CAD $0.89/unit. The proposed model is robust and could also be applied to determine the economic value for feed efficiency traits within a selection index in other production systems and countries.
Objectives: Previous research has demonstrated an association between emotion recognition and apathy in several neurological conditions involving fronto-striatal pathology, including Parkinson’s disease and brain injury. In line with these findings, we aimed to determine whether apathetic participants with early Huntington’s disease (HD) were more impaired on an emotion recognition task compared to non-apathetic participants and healthy controls. Methods: We included 43 participants from the TRACK-HD study who reported apathy on the Problem Behaviours Assessment – short version (PBA-S), 67 participants who reported no apathy, and 107 controls matched for age, sex, and level of education. During their baseline TRACK-HD visit, participants completed a battery of cognitive and psychological tests including an emotion recognition task, the Hospital Depression and Anxiety Scale (HADS) and were assessed on the PBA-S. Results: Compared to the non-apathetic group and the control group, the apathetic group were impaired on the recognition of happy facial expressions, after controlling for depression symptomology on the HADS and general disease progression (Unified Huntington’s Disease Rating Scale total motor score). This was despite no difference between the apathetic and non-apathetic group on overall cognitive functioning assessed by a cognitive composite score. Conclusions: Impairment of the recognition of happy expressions may be part of the clinical picture of apathy in HD. While shared reliance on frontostriatal pathways may broadly explain associations between emotion recognition and apathy found across several patient groups, further work is needed to determine what relationships exist between recognition of specific emotions, distinct subtypes of apathy and underlying neuropathology. (JINS, 2019, 25, 453–461)
In 2011 the Incidence Assay Critical Path Working Group reviewed the current state of HIV incidence assays and helped to determine a critical path to the introduction of an HIV incidence assay. At that time the Consortium for Evaluation and Performance of HIV Incidence Assays (CEPHIA) was formed to spur progress and raise standards among assay developers, scientists and laboratories involved in HIV incidence measurement and to structure and conduct a direct independent comparative evaluation of the performance of 10 existing HIV incidence assays, to be considered singly and in combinations as recent infection test algorithms. In this paper we report on a new framework for HIV incidence assay evaluation that has emerged from this effort over the past 5 years, which includes a preliminary target product profile for an incidence assay, a consensus around key performance metrics along with analytical tools and deployment of a standardized approach for incidence assay evaluation. The specimen panels for this evaluation have been collected in large volumes, characterized using a novel approach for infection dating rules and assembled into panels designed to assess the impact of important sources of measurement error with incidence assays such as viral subtype, elite host control of viraemia and antiretroviral treatment. We present the specific rationale for several of these innovations, and discuss important resources for assay developers and researchers that have recently become available. Finally, we summarize the key remaining steps on the path to development and implementation of reliable assays for monitoring HIV incidence at a population level.
Large floods bringing significant sediments into the coastal oceans have not been observed in Antarctica. We report evidence of a large flood event depositing over 50 cm of sediment onto the nearshore benthic habitat at Salmon Bay, Antarctica, between 1990 and 2010. Besides direct observations of the sedimentation, the evidence involves a debris flow covering old tyre tracks from the early 1960s, as well as evidence of a considerable amount of sediment transported onto the Salmon Creek delta. We believe that the flood was sourced from the Salmon Glacier and possibly the smaller Blackwelder Glacier. Such floods will be more common in the future and it is important to better understand their ecological impacts with good monitoring programmes.
In traditional transit timing variations (TTVs) analysis of multi-planetary systems, the individual TTVs are first derived from transit fitting and later modelled using n-body dynamic simulations to constrain planetary masses. We show that fitting simultaneously the transit light curves with the system dynamics (photo-dynamical model) increases the precision of the TTV measurements and helps constrain the system architecture. We exemplify the advantages of applying this photo-dynamical model to a multi-planetary system found in K2 data very close to 3:2 mean motion resonance, K2-19. In this case the period of the larger TTV variations (libration period) is much longer (>1.5 years) than the duration of the K2 observations (80 days). However, our method allows to detect the short period TTVs produced by the orbital conjunctions between the planets that in turn permits to uniquely characterise the system. Therefore, our method can be used to constrain the masses of near-resonant systems even when the full libration curve is not observed.
Little is known about the relative extent of crime against people with
severe mental illness (SMI).
To assess the prevalence and impact of crime among people with SMI
compared with the general population.
A total of 361 psychiatric patients were interviewed using the national
crime survey questionnaire, and findings compared with those from 3138
general population controls participating in the contemporaneous national
Past-year crime was experienced by 40% of patients v.
14% of controls (adjusted odds ratio (OR) = 2.8, 95% CI 2.0–3.8); and
violent assaults by 19% of patients v. 3% of controls
(adjusted OR = 5.3, 95% CI 3.1–8.8). Women with SMI had four-, ten- and
four-fold increases in the odds of experiencing domestic, community and
sexual violence, respectively. Victims with SMI were more likely to
report psychosocial morbidity following violence than victims from the
People with SMI are at greatly increased risk of crime and associated
morbidity. Violence prevention policies should be particularly focused on
people with SMI.
Domestic and sexual violence are significant public health problems but little is known about the extent to which men and women with severe mental illness (SMI) are at risk compared with the general population. We aimed to compare the prevalence and impact of violence against SMI patients and the general population.
Three hundred and three randomly recruited psychiatric patients, in contact with community services for ⩾1 year, were interviewed using the British Crime Survey domestic/sexual violence questionnaire. Prevalence and correlates of violence in this sample were compared with those from 22 606 general population controls participating in the contemporaneous 2011/12 national crime survey.
Past-year domestic violence was reported by 27% v. 9% of SMI and control women, respectively [odds ratio (OR) adjusted for socio-demographics, aOR 2.7, 95% confidence interval (CI) 1.7–4.0], and by 13% v. 5% of SMI and control men, respectively (aOR 1.6, 95% CI 1.0–2.8). Past-year sexual violence was reported by 10% v. 2.0% of SMI and control women respectively (aOR 2.9, 95% CI 1.4–5.8). Family (non-partner) violence comprised a greater proportion of overall domestic violence among SMI than control victims (63% v. 35%, p < 0.01). Adulthood serious sexual assault led to attempted suicide more often among SMI than control female victims (53% v. 3.4%, p < 0.001).
Compared to the general population, patients with SMI are at substantially increased risk of domestic and sexual violence, with a relative excess of family violence and adverse health impact following victimization. Psychiatric services, and public health and criminal justice policies, need to address domestic and sexual violence in this at-risk group.
Stars are tidally disrupted and accreted when they approach massive black holes (MBHs) closely, producing a flare of electromagnetic radiation. The majority of the (approximately two dozen) tidal disruption events (TDEs) identified so far have been discovered by their luminous, transient X-ray emission. Once TDEs are detected in much larger numbers, in future dedicated transient surveys, a wealth of new applications will become possible. Here, we present the proposed Einstein Probe mission, which is a dedicated time-domain soft X-ray all-sky monitor aiming at detecting X-ray transients including TDEs in large numbers. The mission consists of a wide-field micro-pore Lobster-eye imager (60° × 60°), and is designed to carry out an all-sky transient survey at energies of 0.5-4 keV. It will also carry a more sensitive telescope for X-ray follow-ups, and will be capable of issuing public transient alerts rapidly. Einstein Probe is expected to revolutionise the field of TDE research by detecting several tens to hundreds of events per year from the early phase of flares, many with long-term, well sampled lightcurves.
Thirty pyrite samples from a wide range of localities were analysed using relative comparator and k0 neutron activation analysis (NAA) techniques at the University of Missouri Research Reactor, Columbia, Missouri, USA (MURR) and the Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, Australia (ANSTO), respectively. Statistical analyses of the trace-element data produced by the two methods showed a generally good correlation, with the majority of elemental concentrations of paired data reported by MURR and ANSTO being indistinguishable at a 0.05 significance level. Trace-element analyses of pyrite from Navajún in Spain by both techniques compare well with published data. There is evidence for contamination by Al, Na and Ti in one set of samples, this is likely to have been introduced by contact with a plastic used in sample preparation.
A wave basin experiment has been performed in the MARINTEK laboratories, in one of the largest existing three-dimensional wave tanks in the world. The aim of the experiment is to investigate the effects of directional energy distribution on the statistical properties of surface gravity waves. Different degrees of directionality have been considered, starting from long-crested waves up to directional distributions with a spread of ±30° at the spectral peak. Particular attention is given to the tails of the distribution function of the surface elevation, wave heights and wave crests. Comparison with a simplified model based on second-order theory is reported. The results show that for long-crested, steep and narrow-banded waves, the second-order theory underestimates the probability of occurrence of large waves. As directional effects are included, the departure from second-order theory becomes less accentuated and the surface elevation is characterized by weak deviations from Gaussian statistics.
In this article we measure the impact of gender on women's legislative behavior by utilizing a unique research design. We compare whether women and men of the same political party represent the same congressional district differently with respect to women's issues. Using bill sponsorship and floor remarks during the 104th to 107th sessions of the U.S. House of Representatives as measures of legislative behavior, we find that female legislators who replace men in the same district introduce more women's issues bills in Congress. Although our conclusion that women legislators represent women's issues more frequently in the House supports existing research, our results do so in a new and more effective way by controlling for the competing explanations of party identification and district opinion as factors determining a legislator's behavior.
The WASP consortium is conducting an ultra-wide field survey of stars between 8–15 mag from both hemispheres. Our primary science goal is to detect extra-solar ‘hot-Jupiter’-type planets that eclipse (or transit) bright host stars and for which further detailed investigation will be possible. We summarize the design of the SuperWASP instruments and describe the first results from our northern station SW-N, sited in La Palma, Canary Islands. Our second station, which began operations this year, is located at the South African Astronomical Observatory. Between April and September, 2004, SW-N continuously observed ~6.7 million stars. The consortium's custom-written, fully automated data reduction pipeline has been used to process these data, and the information is now stored in the project archive, held by the Leicester database and archive service (LEDAS). We have applied a sophisticated, automated algorithm to identify the low-amplitude (~0.01 mag), brief (~few hours) signatures of transiting exoplanets. In addition, we have assessed each candidate in the light of all available catalogue information in order to reject data artefacts and astrophysical false positive detections. The highest priority candidates are currently being subjected to further observations in order to select the true planets. Once the exoplanets are confirmed, a host of exciting opportunities are open to us. In this paper, we describe two techniques that exploit the transits in order to detect other objects within the same system. The first involves determining precise epochs for a sequence of transit events in order to detect the small timing variations caused by the gravitational pull of other planets in the same system. The second method employs ultra-high precision photometry of the transits to detect the deviations caused by the presence of exoplanetary moons. Both of these techniques are capable of detecting objects the size of terrestrial planets.
We have conducted a survey of X-ray sources in XMM-Newton observations of M31, examining their power density spectra (PDS) and spectral energy distributions (SEDs). Our automated source detection yielded 535 good X-ray sources; to date, we have studied 225 of them. In particular, we examined the PDS because low mass X-ray binaries (LMXBs) exhibit two distinctive types of PDS. At low accretion rates, the PDS is characterised by a broken power law, with the spectral index changing from $\sim$0 to $\sim$1 at some frequency in the range $\sim$0.01–1 Hz; we refer to such PDS as Type A. At higher accretion rates, the PDS is described by a simple power law; we call these PDS Type B. Of the 225 sources studied to date, 75 exhibit Type A variability, and are almost certainly LMXBs, while 6 show Type B but not Type A, and are likely LMXBs. Of these 81 candidate LMXBs, 71 are newly identified in this survey; furthermore, they are mostly found near the centre of M31. Furthermore, most of the X-ray population in the disc are associated with the spiral arms, making them likely high mass X-ray binaries (HMXBs). In general these HMXBs do not exhibit Type A variability, while many central X-ray sources (LMXBs) in the same luminosity range do. Hence the PDS may distinguish between LMXBs and HMXBs in this luminosity range.
We present preliminary results from a detailed analysis of the X-ray point sources in the XMM-Newton survey of M31 (e.g. Barnard et al. 2005; Pietsch et al. 2005). These sources are expected to be mostly X-ray binaries.