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Neutrophils are implicated in the pathogenesis of many diseases involving inflammation. Neutrophils are also critical to host defence and have a key role in the innate immune response to infection. Despite their efficiencies against a wide range of pathogens however, their ability to contain and combat Mycobacterium tuberculosis (Mtb) in the lung remains uncertain and contentious. The host response to Mtb infection is very complex, involving the secretion of various cytokines and chemokines from a wide variety of immune cells, including neutrophils, macrophages, monocytes, T cells, B cells, NK cells and dendritic cells. Considering the contributing role neutrophils play in the advancement of many diseases, understanding how an inflammatory microenvironment affects neutrophils, and how neutrophils interact with other immune cells, particularly in the context of the infected lung, may aid the design of immunomodulatory therapies. In the current review, we provide a brief overview of the mechanisms that underpin pathogen clearance by neutrophils and discuss their role in the context of Mtb and non-Mtb infection. Next, we examine the current evidence demonstrating how neutrophils interact with a range of human and non-human immune cells and how these interactions can differentially prime, activate and alter a repertoire of neutrophil effector functions. Furthermore, we discuss the metabolic pathways employed by neutrophils in modulating their response to activation, pathogen stimulation and infection. To conclude, we highlight knowledge gaps in the field and discuss plausible novel drug treatments that target host neutrophil metabolism and function which could hold therapeutic potential for people suffering from respiratory infections. [ABSTRACT FROM AUTHOR]

Clinical trial managers play a vital role in the design and conduct of clinical trials in the UK. There is a current recruitment and retention crisis for this specialist role due to a complex set of factors, most likely to have come to a head due to the COVID-19 pandemic. Academic clinical trial units and departments are struggling to recruit trial managers to vacant positions, and multiple influences are affecting the retention of this highly skilled workforce. Without tackling this issue, we face major challenges in the delivery on the Department of Health and Social Care's Future of UK Clinical Research Delivery implementation plan. This article, led by a leading network of and for UK Trial Managers, presents some of the issues and ways in which national stakeholders may be able to address this. [ABSTRACT FROM AUTHOR]

Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23−45%) per protocol, and 51% (95% confidence interval, 40−61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept. [ABSTRACT FROM AUTHOR]

Fluid dynamics have long influenced cells in suspension. Red blood cells and white blood cells are advected through biological microchannels in both the cardiovascular and lymphatic systems and, as a result, are subject to a wide variety of complex fluidic forces as they pass through. In vivo, microfluidic forces influence different biological processes such as the spreading of infection, cancer metastasis, and cell viability, highlighting the importance of fluid dynamics in the blood and lymphatic vessels. This suggests that in vitro devices carrying cell suspensions may influence the viability and functionality of cells. Lab-on-a-chip, flow cytometry, and cell therapies involve cell suspensions flowing through microchannels of approximately 100–800 μ m. This review begins by examining the current fundamental theories and techniques behind the fluidic forces and inertial focusing acting on cells in suspension, before exploring studies that have investigated how these fluidic forces affect the reactions of suspended cells. In light of these studies' findings, both in vivo and in vitro fluidic cell microenvironments shall also be discussed before concluding with recommendations for the field. [ABSTRACT FROM AUTHOR]

We report the results of intensive X-ray, UV, and optical monitoring of the Seyfert 1 galaxy NGC 4593 with Swift. There is no intrinsic flux-related spectral change in any variable component with small apparent variations being due to contamination by a constant hard (reflection) component in the X-rays and the red host galaxy in the UV/optical. Relative to the shortest wavelength band, UVW 2, the lags of the other UV/optical bands mostly agree with the predictions of reprocessing of high energy emission by an accretion disc. The U -band lag is, however, larger than expected, probably because of reprocessed Balmer continuum emission from the distant broad line region (BLR). The UVW 2 band is well correlated with the X-rays but lags by ∼6× more than expected if the UVW 2 results only from reprocessing of X-rays by the disc. However, if the light curves are filtered to remove variations on time-scales >5 d, the lag approaches the expectation from disc reprocessing. memecho analysis shows that direct X-rays can be the driver of most of the UV/optical variations if the response functions have tails up to 10 d, from BLR reprocessing, together with strong peaks at short lag (<1 d) from disc reprocessing. For the 5 AGN monitored so far, the observed UVW 2 to V -band lags are $$\rm{\, \stackrel{\lt }{_\sim }}2$$ of disc reprocessing expectations and vary little between AGN. However, the X-ray to UVW 2 lags greatly exceed disc reprocessing expectations and differ between AGN. The two most absorbed AGN have the largest excesses, so absorption and scattering may affect these lags, but there is no simple relationship between excess and absorption. [ABSTRACT FROM AUTHOR]

We present the results of simultaneous Suzaku and NuSTAR observations of the nearest lowluminosity active galactic nucleus (LLAGN),M81*. The spectrum is well described by a cut-off power law plus narrow emission lines from Fe Kα, Fe xxv, and Fe xxvi. There is no evidence of Compton reflection from an optically thick disc, and we obtain the strongest constraint on the reflection fraction in M81* to date, with a best-fitting value of R = 0.0 with an upper limit of R < 0.1. The Fe Kα line may be produced in optically thin, NH = 1 x 1023 cm-2, gas located in the equatorial plane that could be the broad line region. The ionized iron lines may originate in the hot, inner accretion flow. The X-ray continuum shows significant variability on ~40 ks time-scales suggesting that the primary X-ray source is ~100 s of gravitational radii in size. If this X-ray source illuminates any putative optically thick disc, the weakness of reflection implies that such a disc lies outside a few x10³ gravitational radii. An optically thin accretion flow inside a truncated optically thick disc appears to be a common feature of LLAGN that are accreting at only a tiny fraction of the Eddington limit. [ABSTRACT FROM AUTHOR]

Abstract: The Anatomical Society has developed a series of learning outcomes in consultation with nursing educators delivering anatomical content to undergraduate (preregistration) nursing students. A Delphi panel methodology was adopted to select experts within the field that would recommend core anatomical content in undergraduate nursing programmes throughout the UK. Using the Anatomical Society's Core Gross Anatomy Syllabus for Medical Students as a foundation, a modified Delphi technique was used to develop discipline‐specific outcomes to nursing graduates. The Delphi panel consisted of 48 individuals (n = 48) with a minimum of 3 years' experience teaching anatomy to nursing students, representing a broad spectrum of UK Higher Education Institutions. The output from this study was 64 nursing specific learning outcomes in anatomy that are applicable to all undergraduate (preregistration) programmes in the UK. The new core anatomy syllabus for Undergraduate Nursing offers a basic anatomical framework upon which nurse educators, clinical mentors and nursing students can underpin their clinical practice and knowledge. The learning outcomes presented may be used to develop anatomy teaching within an integrated nursing curriculum. [ABSTRACT FROM AUTHOR]

Background: Accurate detection and estimation of true exposure-outcome associations is important in aetiological analysis; when there are multiple potential exposure variables of interest, methods for detecting the subset of variables most likely to have true associations with the outcome of interest are required. Case-cohort studies often collect data on a large number of variables which have not been measured in the entire cohort (e.g. panels of biomarkers). There is a lack of guidance on methods for variable selection in case-cohort studies.Methods: We describe and explore the application of three variable selection methods to data from a case-cohort study. These are: (i) selecting variables based on their level of significance in univariable (i.e. one-at-a-time) Prentice-weighted Cox regression models; (ii) stepwise selection applied to Prentice-weighted Cox regression; and (iii) a two-step method which applies a Bayesian variable selection algorithm to obtain posterior probabilities of selection for each variable using multivariable logistic regression followed by effect estimation using Prentice-weighted Cox regression.Results: Across nine different simulation scenarios, the two-step method demonstrated higher sensitivity and lower false discovery rate than the one-at-a-time and stepwise methods. In an application of the methods to data from the EPIC-InterAct case-cohort study, the two-step method identified an additional two fatty acids as being associated with incident type 2 diabetes, compared with the one-at-a-time and stepwise methods.Conclusions: The two-step method enables more powerful and accurate detection of exposure-outcome associations in case-cohort studies. An R package is available to enable researchers to apply this method. [ABSTRACT FROM AUTHOR]

Background: Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.Objectives: To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE-LY trial.Methods: HAS-BLED, ORBIT, ATRIA and HEMORR2 HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.Results: There were 1182 (6.5%) major bleeding events during a median follow-up of 2.0 years. For all the four schemes, high-risk subgroups had higher risk of major bleeding (all P < 0.001). The ORBIT score showed the best discrimination with c-indices of 0.66, 0.66 and 0.62, respectively, for major, life-threatening and intracranial bleeding, which were significantly better than for the HAS-BLED score (difference in c-indices: 0.050, 0.053 and 0.048, respectively, all P < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P = 0.0019), ATRIA (P < 0.001) and HEMORR2 HAGES (P < 0.001) scores. HAS-BLED score showed a nonsignificant trend for interaction (P = 0.0607).Conclusions: Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin. [ABSTRACT FROM AUTHOR]

Background: Accurate information on healthcare expenditure is essential; however, a number of issues arise when healthcare expenditure is being measured. Traditionally healthcare expenditure data in Ireland have been limited, especially data that facilitate comparable analysis through time and across particular programmes or services. Recently however, a major development in Irish healthcare expenditure estimates was the publication of Irish healthcare current expenditure estimates for 2013 according to the international standard of the OECD System of Health Accounts (SHA).Aims: The aim of the analysis presented in this paper is to examine how alternative methodologies for measuring healthcare can influence the estimate(s) of healthcare expenditure.Methods: The methods and results (in terms of healthcare expenditure) of the Central Statistics Office (CSO) application of SHA methodology will be compared and contrasted with an alternative methodology for measuring healthcare expenditure developed by Wren et al. [1].Results: The two approaches to measuring healthcare expenditure in Ireland reached a very similar figure for total current healthcare expenditure in 2013. However, there were considerable disparities in the components of expenditure.Conclusions: There is no one absolute definition or estimate of healthcare expenditure, and different methodological approaches to estimating expenditure will likely yield different results. Therefore, care is required when assessing healthcare expenditure to ensure that there is a clear understanding about what is and is not included in the estimate. [ABSTRACT FROM AUTHOR]

Background: National guidance for England recommends that cardiovascular disease (CVD) should be managed as a family of diseases in the community. Here, we describe the results of such an approach.Methods: Patients with established CVD or who were at high multifactorial risk (HRI) underwent a 12-week community-based nurse-led prevention programme (MyAction) that included lifestyle and risk factor management, prescription of medication and weekly exercise and education sessions.Results: Over a 6-year period, 3232 patients attended an initial assessment; 63% were male, and 48% belonged to black and minority ethnic groups. 56% attended an end-of-programme assessment, and 33% attended a one year assessment. By the end of the programme, there was a significant reduction in smoking prevalence but only in HRI (-3.7%, p<0.001). Mediterranean diet score increased in both CVD (+1.2, p<0.001) and HRI (+1.5; p<0.001), as did fitness levels (CVD +0.8 estimated Mets maximum, p<0.001, HRI +0.9 estimated Mets maximum, p<0.001) and the proportions achieving their physical activity targets (CVD +40%, p<0.001, HRI +37%, p<0.001). There were significant increases in proportions achieving their blood pressure (CVD +15.4%, p<0.001, HRI +25%, p<0.001 and low-density lipoprotein cholesterol targets (CVD +6%, p=0.004, HRI +23%, p<0.001). Statins and antihypertensive medications significantly increased in HRI. Significant improvements in depression scores and quality-of-life measures were also seen. The majority of improvements were maintained at 1 year.Conclusion: These results demonstrate that an integrated vascular prevention programme is feasible in practice and reduces cardiovascular risk in patients with established CVD and in those at high multifactorial risk. [ABSTRACT FROM AUTHOR]

Predicted increases in sea-surface temperatures due to climate change are likely to alter the physiology of marine organisms and ultimately influence the distribution and abundance of their populations. The consequences of increased temperatures for marine species, including decreased survival and altered rates of development, growth and settlement, are well known and often attributed to imbalances between energy supply and demand. To test this hypothesis, we calibrated the effect of temperature on rates of survival and lipid depletion for larvae of the common stony coral Acropora tenuis over a 7 °C temperature range. Temperature had a pronounced, linearly increasing effect on larval mortality, with a sixfold decrease in median survival time. Contrary to expectation, however, temperature had a quasi-parabolic effect on lipid use; rates declined as temperatures either increased above or decreased below the ambient temperature at the time of spawning. This contrasts with previous work suggesting that increased energy depletion is the cause of larval mortality at higher temperatures. Our results highlight the sensitivity of coral larvae to temperature and have implications for dispersal potential because fewer larvae will survive to disperse. Such projected declines in connectivity among coral populations are likely to undermine reef resilience. [ABSTRACT FROM AUTHOR]

We present X-ray spectral variability of 24 local active galactic nuclei (AGN) from the Palomar sample of nearby galaxies, as observed mainly by Swift. From hardness ratio measurements, we find that 18 AGN with low accretion rates show hardening with increasing count rate, converse to the softer-when-brighter behaviour normally observed in AGN with higher accretion rates. Two AGN show softening with increasing count rate, two show more complex behaviour, and two do not show any simple relationship. Sufficient data were available for the spectra of 13 AGN to be summed in flux-bins. In nine of these sources, correlated luminosity-dependent changes in the photon index (Γ) of a power-law component are found to be the main cause of hardness variability. For six objects, with a low accretion rate as a fraction of the Eddington rate (mEdd), Γ is anticorrelated with mEdd, i.e. 'harder-when-brighter' behaviour is observed. The three higher mEdd-rate objects show a positive correlation between Γ and mEdd. This transition from harder-when-brighter at low mEddto softer-when-brighter at high mEdd can be explained by a change in the dominant source of seed-photons for X-ray emission from cyclosynchrotron emission from the Comptonizing corona itself to thermal seed-photons from the accretion disc. This transition is also seen in the 'hard state' of black hole X-ray binaries (BHXRBs). The results support the idea that low-ionization nuclear emission-line regions are analogues of BHXRBs in the hard state and that Seyferts are analogues of BHXRBs in either the high-accretion rate end of the hard state or in the hard-intermediate state. [ABSTRACT FROM AUTHOR]

The origin of short timescale (weeks/months) variability of AGN, whether due to intrinsic disc variations or reprocessing of X-ray emission by a surrounding accretion disc, has been a puzzle for many years. However recently a number of observational programmes, particularly of NGC 5548 with Swift, have shown that the UV/optical variations lag behind the X-ray variations in a manner strongly supportive of X-ray reprocessing. Somewhat surprisingly, the implied size of the accretion disc is ∼3 times greater than expected from a standard, smooth, Shakura-Sunyaev thin disc model. Although the difference may be explained by a clumpy accretion disc, it is not clear whether the difference will occur in all AGN or whether it may change as, eg, a function of black hole mass, accretion rate, or disc temperature. Measurements of interband lags for most AGN require long timescale monitoring, which is hard to arrange. However for low mass (<106 M⊙) AGN, the combination of XMM- Newton EPIC (X-rays) with the optical monitor in fast readout mode allows an X-ray/UV-optical lag to be measured within a single long observation. Here we summarise previous related observations and report on XMM- Newton observations of NGC 4395 (mass 100 times lower, accretion rate ∼20 times lower than for NGC 5548). We find that the UVW1 lags the X-rays by ∼470 s. Simultaneous observations at 6 different ground based observatories also allowed the g-band lag (∼800 s) to be measured. These observations are in agreement with X-ray reprocessing but initial analysis suggests that, for NGC 4395, they do not differ markedly from the predictions of the standard thin disc model. (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

The increased demand for animal-derived protein and energy for human consumption will have to be achieved through a combination of improved animal genetic merit and better management strategies. The objective of the present study was to quantify whether differences in genetic merit among animals materialised into phenotypic differences in commercial herds. Carcass phenotypes on 156 864 animals from 7301 finishing herds were used, which included carcass weight (kg), carcass conformation score (scale 1 to 15), carcass fat score (scale 1 to 15) at slaughter as well as carcass price. The price per kilogram and the total carcass value that the producer received for the animal at slaughter was also used. A terminal index, calculated in the national genetic evaluations, was obtained for each animal. The index was based on pedigree index for calving performance, feed intake and carcass traits from the national genetic evaluations. Animals were categorised into four terminal index groups on the basis of genetic merit estimates that were derived before the expression of the phenotypic information by the validation animals. The association between terminal index and phenotypic performance at slaughter was undertaken using mixed models; whether the association differed by gender (i.e. young bulls, steers and heifers) or by early life experiences (animals born in a dairy herd or beef herd) was also investigated. The regression coefficient of phenotypic carcass weight, carcass conformation and carcass fat on their respective estimated breeding values (EBVs) was 0.92 kg, 1.08 units and 0.79 units, respectively, which is close to the expectation of one. Relative to animals in the lowest genetic merit group, animals in the highest genetic merit group had, on average, a 38.7 kg heavier carcass, with 2.21 units greater carcass conformation, and 0.82 units less fat. The superior genetic merit animals were, on average, slaughtered 6 days younger than their inferior genetic merit contemporaries. The superior carcass characteristics of the genetically elite animals materialised in carcasses worth €187 more than those of the lowest genetic merit animals. Although the phenotypic difference in carcass traits of animals divergent in terminal index differed statistically by animal gender and early life experience, the detected interactions were generally biologically small. This study clearly indicates that selection on an appropriate terminal index will produce higher performing animals and this was consistent across all production systems investigated. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Large-scale expansion of no-take closures within the Great Barrier Reef has not enhanced fisheries production," by W. J. Fletcher and colleagues in the 2015 issue.

Territories of grazing fishes in the family Pomacentridae have been documented to cover a substantial proportion of shallow, exposed coral reef fronts, and these fishes can have profound effects on benthic community composition, including the recruitment and post-settlement survival of scleractinian corals. However, current studies of territorial grazer effects on corals have focused on back-reef habitats. Territorial damselfishes occur in distinct behavioural guilds ranging from indeterminate territorial grazers with thin algal turfs and low rates of territorial aggression to intensive territorial grazers with thick turfs and high rates of aggression. To determine the impact of territorial grazers on the establishment of juvenile corals, we surveyed the reef crest habitat of Lizard Island, Great Barrier Reef, using fixed transects to assess the effects of indeterminate and intensive territorial grazers on juvenile coral abundance and taxonomic composition. In addition, the turnover of territorial pomacentrids was monitored as well as the effects of turnover on juvenile coral assemblages. Intensive territorial grazers were associated with a significantly lower juvenile coral abundance (34 % decrease), but neither intensive nor indeterminate grazer territories impacted juvenile coral taxonomic composition. Over the course of 1 yr, there was a high rate of territorial turnover (39.7 %). Turnover from control plots to intensive damselfish territories was accompanied by a 44 % decrease in juvenile corals; conversely, turnover from intensive damselfish territories to control plots coincided with a 48 % increase in juvenile corals. These findings reveal two main conclusions. Firstly, the association between damselfish territories and the abundance and spatial turnover of juvenile corals strongly implies that territorial grazers have a negative effect on juvenile coral populations. Secondly, the unexpectedly high temporal turnover of damselfish territories indicates that damselfish-coral-algae linkages are highly dynamic, may be extensively influenced by local-scale effects, and have the potential to impact the structure of coral assemblages on coral reef fronts. [ABSTRACT FROM AUTHOR]

Lags measured from correlated X-ray/UV/optical monitoring of AGN allow us to determine whether UV/optical variability is driven by reprocessing of X-rays or X-ray variability is driven by UV/optical seed photon variations. We present the results of the largest study to date of the relationship between the X-ray, UV and optical variability in an AGN with 554 observations, over a 750 d period, of the Seyfert 1 galaxy NGC 5548 with Swift. There is a good overall correlation between the X-ray and UV/optical bands, particularly on short time-scales (tens of days). The UV/optical bands lag the X-ray band with lags which are proportional to wavelength raised to the power 1.23 ± 0.31. This power is very close to the power (4/3) expected if short time-scale UV/optical variability is driven by reprocessing of X-rays by a surrounding accretion disc. The observed lags, however, are longer than expected from a standard Shakura–Sunyaev accretion disc with X-ray heating, given the currently accepted black hole mass and accretion rate values, but can be explained with a slightly larger mass and accretion rate, and a generally hotter disc. Some long-term UV/optical variations are not paralleled exactly in the X-rays, suggesting an additional component to the UV/optical variability arising perhaps from accretion rate perturbations propagating inwards through the disc. [ABSTRACT FROM PUBLISHER]

We present long-term (months–years) X-ray spectral variability of the Seyfert 1.8 galaxy NGC 1365 as observed by Swift, which provides well-sampled observations over a much longer timescale (six years) and a much larger flux range than is afforded by other observatories. At very low luminosities, the spectrum is very soft, becoming rapidly harder as the luminosity increases and then, above a particular luminosity, softening again. At a given flux level, the scatter in hardness ratio is not very large, meaning that the spectral shape is largely determined by the luminosity. The spectra were therefore summed in luminosity bins and fitted with a variety of models. The best-fitting model consists of two power laws, one unabsorbed and another, more luminous, which is absorbed. In this model, we find a range of intrinsic 0.5–10.0 keV luminosities of approximately 1.1–3.5 erg s−1, and a very large range of absorbing columns, of approximately 1022–1024 cm−2. Interestingly, we find that the absorbing column decreases with increasing luminosity, but that this result is not due to changes in ionization. We suggest that these observations might be interpreted in terms of a wind model in which the launch radius varies as a function of ionizing flux and disc temperature and therefore moves out with increasing accretion rate, i.e. increasing X-ray luminosity. Thus, depending on the inclination angle of the disc relative to the observer, the absorbing column may decrease as the accretion rate goes up. The weaker, unabsorbed, component may be a scattered component from the wind. [ABSTRACT FROM AUTHOR]

We present phase-resolved spectroscopic observations of the low-mass X-ray binary V926 Sco (4U 1735-44), covering the orbital period of 0.23 days, obtained with the Walter Baade 6.5 m Magellan Telescope at the Las Campanas Observatory in 2010 June and 2011 June. We use Hα radial velocities to derive a systemic velocity of –109 ± 4 km s–1. The FWHM of the lines observed in common with previous authors are significantly lower during our observations suggesting much reduced velocities in the system. The equivalent width of the Bowen fluorescence lines with respect to He II λ4686 are factors of two or more lower during our observations in comparison to those previously reported for the system, suggesting reduced irradiation of the secondary. Doppler and modulation tomography of Hα and He II λ4686 show asymmetric emission that can be attributed to a bulge in the accretion disk, as inferred from He II observations by previous authors. The X-ray fluxes from the source at times concurrent with the optical observations are significantly lower during our observations than during optical observations taken in 2003. We suggest that the system is in a lower accretion state compared to earlier observations; this explains both the lower velocities observed from the disk and the reduction of emission due to Bowen fluorescence detected from the secondary. [ABSTRACT FROM AUTHOR]

Aim We incorporate diversity-dependent colonization and extinction rates into process-based models of species geographic range dynamics to explore their effects on species richness gradients, and on extent and occupancy of species ranges. In particular, we investigate whether diversity dependence promotes or inhibits the emergence of mid-domain effects ( MDEs) in homogeneous environments. Location A theoretical one-dimensional domain. Methods We formulated diversity-independent ( DI) and diversity-dependent ( DD) models that simulated colonization, local extinction and speciation within a homogenous domain. In the DD model, colonization and extinction probabilities were functions of diversity, whereas in the DI model, they were constants. For a wide range of parameter values, we examined local and regional species richness gradients and species range size frequency distributions ( RSFDs). Results In contrast to the DI model, for which MDEs only occurred in a very narrow parameter range, the DD model generated a MDE in regional richness (range overlap) that was robust to colonization and extinction parameters, over a broad range of speciation rates. However, neither model could produce gradients in local richness (patch occupancy). The DD model also produced more realistic RSFDs than the DI model. In the latter, all species generally either became highly pandemic or went globally extinct, depending on the balance of colonization and extinction probabilities. Main conclusions Diversity-dependent colonization and extinction rates can have strong effects on species richness gradients and distributions of range extent and occupancy. Models with such diversity dependence amplify MDEs in regional richness, but largely eliminate MDEs in local richness, relative to DI models. DD models also generate more realistic RSFDs. These findings suggest that diffuse species interactions can strongly influence patterns of range size and overlap, but also that environmental gradients are likely to be necessary to explain many species richness patterns in nature, which exhibit both local and regional diversity gradients. [ABSTRACT FROM AUTHOR]

Atrial fibrillation ( AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists ( VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio ( INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice. [ABSTRACT FROM AUTHOR]

Lecithotrophic, or non-feeding, marine invertebrate larvae generally have shorter pelagic larval durations (PLDs) than planktotrophic larvae. However, non-feeding larvae of scleractinian corals have PLDs far exceeding those of feeding larvae of other organisms and predictions of PLD based on energy reserves and metabolic rates, raising questions about how such longevity is achieved. Here, we measured temporal changes in metabolic rates and total lipid content of non-feeding larvae of four species of reef corals to determine whether changes in energy utilization through time contribute to extended larval durations. The temporal dynamics of both metabolic rates and lipid content were highly consistent among species. Prior to fertilization, metabolic rates were low (2.73-8.63 nmol O larva h) before rapidly increasing to a peak during embryogenesis and early development 1-2 days after spawning. Metabolic rates remained high until shortly after larvae first became competent to metamorphose and then declined by up to two orders of magnitude to levels at or below rates seen in unfertilized eggs over the following week. Larvae remained in this state of low metabolic activity for up to 2 months. Consistent with temporal patterns in metabolic rates, depletion of lipids was extremely rapid during early development and then slowed dramatically from 1 week onward. Despite the very low metabolic rates in these species, larvae continued to swim and retained competence for at least 2 months. The capacity of non-feeding coral larvae to enter a state of low metabolism soon after becoming competent to metamorphose significantly extends dispersal potential, thereby accruing advantages typically associated with planktotrophy, notably enhanced population connectivity. [ABSTRACT FROM AUTHOR]

Background: In the absence of reliable, objective and direct measures of awareness, the diagnosis and prognosis of the vegetative and minimally conscious states are greatly complicated. This has led to an unacceptably high level of misdiagnosis. Although diagnosis and prognosis have typically relied on bedside behavioural measures, a number of recent studies on neuroimaging and neurophysiological methods offer the possibility of improvement in these areas. Objectives: We examined current clinical practice and possible future directions in the diagnosis, prognosis and treatment of disorders of consciousness, as well as the ethical and legal dilemmas associated with these disorders. We also summarise epidemiological data from three specialist rehabilitation hospitals in Ireland. Conclusions: We recommend an international agreement on standard behavioural assessment. This would enable greater consistency in diagnosis and prognostication, as well as improved accuracy of epidemiological data. Based on the current evidence, we advocate the introduction of neuroimaging and neurophysiological techniques into the standardised investigation profile. A more detailed epidemiological study is also required in Ireland. [ABSTRACT FROM AUTHOR]

Coral bleaching and disease have often been hypothesized to be mutually reinforcing or co-occurring, but much of the research supporting this has only drawn an implicit connection through common environmental predictors. In this study, we examine whether an explicit relationship between white syndrome and bleaching exists using assemblage-level monitoring data from up to 112 sites on reef slopes spread throughout the Great Barrier Reef over 11 years of monitoring. None of the temperature metrics commonly used to predict mass bleaching performed strongly when applied to these data. Furthermore, the inclusion of bleaching as a predictor did not improve model skill over baseline models for predicting white syndrome. Similarly, the inclusion of white syndrome as a predictor did not improve models of bleaching. Evidence for spatial co-occurrence of bleaching and white syndrome at the assemblage level in this data set was also very weak. These results suggest the hypothesized relationship between bleaching and disease events may be weaker than previously thought, and more likely to be driven by common responses to environmental stressors, rather than directly facilitating one another. [ABSTRACT FROM AUTHOR]

Bleaching in corals due to environmental stress represents a loss of energy intake often leading to an increase in mortality risk. Successful coral recovery from severe bleaching events may depend on the rate of replenishment of algal symbiont populations following the period of thermal stress, the supply of an alternative food source, or both. Here, we explore the role of food availability in promoting the survival and recovery of a common coral ( Acropora intermedia) following acute experimentally induced thermal stress. Fed corals were provided with live rotifers daily, to maintain densities of zooplankton in tanks that are typical of coral reefs. After a 6-week acclimation phase, heated corals were subjected to a +4 °C thermal anomaly for a 7-day period (bleaching phase) then temperatures were returned to normal for a further 2 weeks (recovery phase). Results demonstrated that heated corals had higher survival when they were provided with heterotrophic food. Fed corals experienced reduced loss of chlorophyll a, relative to unfed corals. During the recovery phase, both fed and unfed corals recovered within a few days; however, fed corals recovered to pre-bleaching phase levels of chlorophyll a, whereas unfed corals stabilized approximately one-third below this level. Protein levels of fed corals declined markedly during the bleaching phase, but recovered all of their losses by the end of the recovery phase. In contrast, unfed corals had low protein levels that were maintained throughout the experiment. To the extent that these results are representative of corals' responses to thermal anomalies in nature, the findings imply that availability of particulate food matter has the potential to increase corals' capacity to survive thermally induced bleaching and to ameliorate its sub-lethal effects. They also support the hypothesis that different rates of heterotrophy are an important determinant of variation in resilience to thermal stress among reef environments. [ABSTRACT FROM AUTHOR]

M c HUGH J.C., TRYFONOPOULOS D., FENNELLY D., CROWN J. & CONNOLLY S. (2012) European Journal of Cancer Care Electroclinical biomarkers of early peripheral neurotoxicity from oxaliplatin Peripheral neuropathy is the principal dose-limiting side effect of chemotherapy with oxaliplatin. Early biomarkers of oxaliplatin-related neuropathy (ON) are important for guiding management and as outcomes for neuroprotective trials. We compared a number of clinical and neurophysiological techniques to identify early features of ON. Median nerve motor excitability testing, nerve conduction studies, vibration perception threshold (VPT) and clinical assessments were carried out on 17 patients and 105 controls. Neuropathy was graded using the total neuropathy score and National Cancer Institute Common Toxicity Criteria scales. Oxaliplatin causes a length-dependent sensory neuropathy. The most sensitive early marker of neuropathy was abnormal VPT in the foot followed by diminished sensory nerve action potential amplitudes. Median nerve excitability studies revealed no biologically significant effects of treatment on motor axons. VPT is an easily applicable and effective marker of neuropathy at low cumulative doses of oxaliplatin. Nerve excitability measures may be useful in predicting ON but motor studies do not reveal early cumulative changes following treatment with the drug. [ABSTRACT FROM AUTHOR]

Increasingly, ICD implantation is performed without defibrillation testing (DT). To determine the current frequency of DT, the risks associated with DT, and to understand how physicians select patients to have DT. Between January 2007 and July 2008, all patients in Ontario, Canada who received an ICD were enrolled in this prospective registry. A total of 2,173 patients were included; 58% had new ICD implants for primary prevention, 25% for secondary prevention, and 17% had pulse generator replacement. DT was carried out at the time of ICD implantation or predischarge in 65%, 67%, and 24% of primary, secondary, and replacement cases respectively (P = <0.0001). The multivariate predictors of a decision to conduct DT included: new ICD implant (OR = 13.9, P < 0.0001), dilated cardiomyopathy (OR = 1.8, P < 0.0001), amiodarone use (OR = 1.5, P = 0.004), and LVEF > 20% (OR = 1.3, P = 0.05). A history of atrial fibrillation (OR = 0.58, P = 0.0001) or oral anticoagulant use (OR = 0.75, P = 0.03) was associated with a lower likelihood of having DT. Age, gender, NYHA class, and history of stroke or TIA did not predict DT. Perioperative complications, including death, myocardial infarction, stroke, tamponade, pneumothorax, heart failure, infection, wound hematoma, and lead dislodgement, were similar among patients with (8.7%) and without (8.3%) DT (P = 0.7) DT is performed in two-thirds of new ICD implants but only one-quarter of ICD replacements. Physicians favored performance of DT in patients who are at lower risk of DT-related complications and in those receiving amiodarone. DT was not associated with an increased risk of perioperative complications. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1344-1348, December 2010) [ABSTRACT FROM AUTHOR]