Short communication: a survey of grass-clover ley management and creation of a near infra-red reflectance spectroscopy equation to predict clover concentration

The purpose of the present study was, firstly, to examine current practice for the agronomy of grass-clover mixed swards used for silage-making in the UK, and secondly, to develop and validate a Near Infra-Red Reflectance Spectroscopy (NIRS) equation capable of predicting clover concentration (CC) in undried and unmilled grass-clover silage samples. A calibration set of 94 grass-clover (white, trifolium repens, and red, trifolium pratense) mixture silage samples were sourced from UK farms and an accompanying questionnaire was used to obtain information on the sward agronomy used to produce each sample. Questionnaire data highlighted that (i) reducing the use of fertiliser inputs (ii) increasing uptake of new varieties, and (iii) increasing the farmer’s ability to measure botanical composition as potential strategies for improving the utilisation of clover in grass swards. Botanical composition was measured by hand separation for each sample and a new NIRS equation was created and assessed using blind validation with an independent set of 30 grass-clover samples. The relative standard error of cross validation (SECV, as a percentage of the measured mean) of the optimised equation produced was 36.8%, and, in an independent validation test, the ratio of standard error of prediction to the standard deviation of the reference data set (RPD) was 1.56. The equation could be improved by increasing accuracy at high CCs but showed promise as a simple tool to assist growers in sward management decisions

Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study

AIMS: To examine the changes in coronary, all-cause, and cancer mortality in patients with heterozygous familial hypercholesterolaemia (FH) before and after lipid-lowering therapy with statins. METHODS AND RESULTS: A total of 3382 patients (1650 men) aged <80 years were recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2006 for 46 580 person-years. There were 370 deaths, including 190 from coronary heart disease (CHD) and 90 from cancer. The standardized mortality ratio (compared with the population in England and Wales) was calculated before and from 1 January 1992. In patients aged 20-79 years, CHD mortality fell significantly by 37% (95% CI = 7-56) from 3.4- to 2.1-fold excess. Primary prevention resulted in a 48% reduction in CHD mortality from 2.0-fold excess to none, with a smaller reduction of nearly 25% in patients with established disease. Coronary mortality was reduced more in women than in men. In patients without known CHD at registration, all-cause mortality from 1992 was 33% (21-43), lower than in the general population, mainly due to a 37% (21-50) lower risk of fatal cancer. CONCLUSION: The results emphasize the importance of early identification of FH and treatment with statins

Comparison Between Diffusion-Weighted MRI and I-123-mIBG Uptake in Primary High-Risk Neuroblastoma

Background: High-risk neuroblastoma (HR-NB) has a variable response to preoperative chemotherapy. It is not possible to differentiate viable vs. nonviable residual tumor before surgery. Purpose: To explore the association between apparent diffusion coefficient (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI), 123I-meta-iodobenzyl-guanidine (123I-mIBG) uptake, and histology before and after chemotherapy. Study Type: Retrospective. Subjects: Forty patients with HR-NB. Field Strength/Sequence: 1.5T axial DW-MRI (b = 0,1000 s/mm2 ) and T2-weighted sequences. 123I-mIBG scintigraphy planar imaging (all patients), with additional 123I-mIBG single-photon emission computed tomography / computerized tomography (SPECT/CT) imaging (15 patients). Assessment: ADC maps and 123I-mIBG SPECT/CT images were coregistered to the T2-weighted images. 123I-mIBG uptake was normalized with a tumor-to-liver count ratio (TLCR). Regions of interest (ROIs) for primary tumor volume and different intratumor subregions were drawn. The lower quartile ADC value (ADC25prc) was used over the entire tumor volume and the overall level of 123I-mIBG uptake was graded into avidity groups. Statistical Tests: Analysis of variance (ANOVA) and linear regression were used to compare ADC and MIBG values before and after treatment. Threshold values to classify tumors as viable/necrotic were obtained using ROC analysis of ADC and TLCR values. Results: No significant difference in whole-tumor ADC25prc values were found between different 123I-mIBG avidity groups pre- (P = 0.31) or postchemotherapy (P = 0.35). In the “intratumor” analysis, 5/15 patients (prechemotherapy) and 0/14 patients (postchemotherapy) showed a significant correlation between ADC and TLCR values (P < 0.05). Increased tumor shrinkage was associated with lower pretreatment tumor ADC25prc values (P < 0.001); no association was found with pretreatment 123I-mIBG avidity (P = 0.17). Completely nonviable tumors had significantly lower postchemotherapy ADC25prc values than tumors with >10% viable tumor (P < 0.05). Both pre- and posttreatment TLCR values were significantly higher in patients with >50% viable tumor than those with 10–50% viable tumor (P < 0.05). Data Conclusion: 123I-mIBG avidity and ADC values are complementary noninvasive biomarkers of therapeutic response in HR-NB. Level of Evidence: 4. Technical Efficacy Stage: 3

Effect of linseed oil and fish oil alone or as an equal mixture on ruminal fatty acid metabolism in growing steers fed maize silage-based diets

Based on the potential benefits to human health there is interest in increasing 18:3n-3, 20:5n-3, 22:6n-6, and cis-9,trans-11 conjugated linoleic acid (CLA) in ruminant foods. Four Aberdeen Angus steers (406 ± 8.2 kg BW) fitted with rumen and duodenal cannulae were used in a 4 x 4 Latin square experiment with 21 d periods to examine the potential of fish oil (FO) and linseed oil (LO) in the diet to increase ruminal outflow of trans-11 18:1 and total n-3 polyunsaturated fatty acids (PUFA) in growing cattle. Treatments consisted of a control diet (60:40; forage:concentrate ratio, on a DM basis, respectively) based on maize silage, or the same basal ration containing 30 g/kg DM of FO, LO or a mixture (1:1, w/w) of FO and LO (LFO). Diets were offered as total mixed rations and fed at a rate of 85 g DM/kg BW0.75/d. Oils had no effect (P = 0.52) on DM intake. Linseed oil had no effect (P > 0.05) on ruminal pH or VFA concentrations, while FO shifted rumen fermentation towards propionate at the expense of acetate. Compared with the control, LO increased (P < 0.05) 18:0, cis 18:1 (Δ9, 12-15), trans 18:1 (Δ4-9, 11-16), trans 18:2, geometric isomers of ∆9,11, ∆11,13, and ∆13,15 CLA, trans-8,cis-10 CLA, trans-10,trans-12 CLA, trans-12,trans-14 CLA, and 18:3n-3 flow at the duodenum. Inclusion of FO in the diet resulted in higher (P < 0.05) flows of cis-9 16:1, trans 16:1 (Δ6-13), cis 18:1 (Δ9, 11, and 13), trans 18:1 (Δ6-15), trans 18:2, 20:5n-3, 22:5n-3, and 22:6n-3, and lowered (P < 0.001) 18:0 at the duodenum relative to the control. For most fatty acids at the duodenum responses to LFO were intermediate of FO and LO. However, LFO resulted in higher (P = 0.04) flows of total trans 18:1 than LO and increased (P < 0.01) trans-6 16:1 and trans-12 18:1 at the duodenum compared with FO or LO. Biohydrogenation of cis-9 18:1 and 18:2n-6 in the rumen was independent of treatment, but both FO and LO increased (P < 0.001) the extent of 18:3n-3 biohydrogenation compared with the control. Ruminal 18:3n-3 biohydrogenation was higher (P < 0.001) for LO and LFO than FO, while biohydrogenation of 20:5n-3 and 22:6n-3 in the rumen was marginally lower (P = 0.05) for LFO than FO. In conclusion, LO and FO at 30 g/kg DM altered the biohydrogenation of unsaturated fatty acids in the rumen causing an increase in the flow of specific intermediates at the duodenum, but the potential of these oils fed alone or as a mixture to increase n-3 PUFA at the duodenum in cattle appears limited

Reconstructing the three-dimensional GABAergic microcircuit of the striatum

A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study

Index

The interest in relativistic beam-plasma instabilities has been greatly rejuvenated over the past two decades by novel concepts in laboratory and space plasmas. Recent advances in this long-standing field are here reviewed from both theoretical and numerical points of view. The primary focus is on the two-dimensional spectrum of unstable electromagnetic waves growing within relativistic, unmagnetized, and uniform electron beam-plasma systems. Although the goal is to provide a unified picture of all instability classes at play, emphasis is put on the potentially dominant waves propagating obliquely to the beam direction, which have received little attention over the years. First, the basic derivation of the general dielectric function of a kinetic relativistic plasma is recalled. Next, an overview of two-dimensional unstable spectra associated with various beam-plasma distribution functions is given. Both cold-fluid and kinetic linear theory results are reported, the latter being based on waterbag and Maxwell–Jüttner model distributions. The main properties of the competing modes (developing parallel, transverse, and oblique to the beam) are given, and their respective region of dominance in the system parameter space is explained. Later sections address particle-in-cell numerical simulations and the nonlinear evolution of multidimensional beam-plasma systems. The elementary structures generated by the various instability classes are first discussed in the case of reduced-geometry systems. Validation of linear theory is then illustrated in detail for large-scale systems, as is the multistaged character of the nonlinear phase. Finally, a collection of closely related beam-plasma problems involving additional physical effects is presented, and worthwhile directions of future research are outlined.Original Publication: Antoine Bret, Laurent Gremillet and Mark Eric Dieckmann, Multidimensional electron beam-plasma instabilities in the relativistic regime, 2010, Physics of Plasmas, (17), 12, 120501-1-120501-36. http://dx.doi.org/10.1063/1.3514586 Copyright: American Institute of Physics http://www.aip.org/</p

Systemic anticoagulation in the setting of vascular extremity trauma

Introduction There is conflicting data regarding if patients with vascular extremity trauma who undergo surgical treatment need to be systematically anticoagulated. We hypothesized that intraoperative systemic anticoagulation (ISA) decreased the risk of repair thrombosis or limb amputation after traumatic vascular injury of the extremities. Methods We analyzed a composite risk of repair thrombosis and/or limb amputation (RTLA) between patients who did and did not undergo ISA during arterial injury repair. Patient data was collected in the American Association for the Surgery of Trauma PROspective Vascular Injury Treatment (PROOVIT) registry. This registry contains demographic, diagnostic, treatment, and outcome data. Results Between February 2013 and August 2015, 193 patients with upper or lower extremity arterial injuries who underwent open operative repair were entered into the PROOVIT registry. The majority were male (87%) with a mean age of 32.6 years (range 4–91) and 74% injured by penetrating mechanism. 63% of the injuries were described as arterial transection and 37% had concomitant venous injury. 62% of patients underwent ISA. RTLA occurred in 22 patients (11%) overall, with no significant difference in these outcomes between patients who received ISA and those that did not (10% vs. 14%, p = 0.6). There was, however, significantly higher total blood product use noted among patients treated with ISA versus those that did not receive ISA (median 3 units vs. 1 unit, p = 0.002). Patients treated with ISA also stayed longer in the ICU (median 3 days vs. 1 day, p = 0.001) and hospital (median 9.5 days vs. 6 days, p = 0.01). Discussion In this multicenter prospective cohort, intraoperative systemic anticoagulation was not associated with a difference in rate of repair thrombosis or limb loss; but was associated with an increase in blood product requirements and prolonged hospital stay. Our data suggest there is no significant difference in outcome to support use of ISA for repair of traumatic arterial injuries

Centrifugal separation and equilibration dynamics in an electron-antiproton plasma

Charges in cold, multiple-species, non-neutral plasmas separate radially by mass, forming centrifugally-separated states. Here, we report the first detailed measurements of such states in an electron-antiproton plasma, and the first observations of the separation dynamics in any centrifugally-separated system. While the observed equilibrium states are expected and in agreement with theory, the equilibration time is approximately constant over a wide range of parameters, a surprising and as yet unexplained result. Electron-antiproton plasmas play a crucial role in antihydrogen trapping experiments

A cycle of brain gain, waste and drain - a qualitative study of non-EU migrant doctors in Ireland.

BACKGROUND: Ireland is heavily reliant on non-EU migrant health workers to staff its health system. Shortages of locally trained health workers and policies which facilitate health worker migration have contributed to this trend. This paper provides insight into the experiences of non-EU migrant doctors in the Irish health workforce. METHOD: In-depth interviews were conducted with 37 non-EU migrant doctors in Ireland in 2011/2012. RESULTS: Respondents believed they had been recruited to fill junior hospital doctor 'service' posts. These posts are unpopular with locally trained doctors due to the limited career progression they provide. Respondents felt that their hopes for career progression and postgraduate training in Ireland had gone unrealised and that they were becoming de-skilled. As a result, most respondents were actively considering onward migration from Ireland. DISCUSSION & CONCLUSIONS: Failure to align the expectations of non-EU migrant doctors with the requirements of the health system has resulted in considerable frustration and a cycle of brain gain, waste and drain. The underlying reasons for high mobility into and out of the Irish medical workforce must be addressed if this cycle is to be broken. The heavy reliance on non-EU migrant doctors to staff the medical workforce has distracted from the underlying workforce challenges facing the Irish medical workforce

Functional analysis of four LDLR 5'UTR and promoter variants in patients with familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disease characterised by increased low-density lipoprotein cholesterol (LDL-C) levels. The functionality of four novel variants within the LDLR 5'UTR and promoter located at c.-13A>G, c.-101T>C, c.-121T>C and c.-215A>G was investigated using in silico and in vitro assays, and a systemic bioinformatics analysis of all 36 reported promoter variants are presented. Bioinformatic tools predicted that all four variants occurred in sites likely to bind transcription factors and that binding was altered by the variant allele. Luciferase assay was performed for all the variants. Compared with wild type, the c.-101T>C and c.-121T>C variants showed significantly lower mean (±SD) luciferase activity (64±8 and 72±8%, all PG or c.-215A>G variants (96±15 and 100±12%), suggesting these variants are not FH causing. Similar results were seen for the c.-101T>C and c.-121T>C variants in lipid-depleted serum. However, a significant reduction in luciferase activity was seen in the c.-215A>G variant in lipid-depleted serum. Electrophoretic-mobility shift assays identified allele-specific binding of liver (hepatoma) nuclear proteins to c.-121T>C and suggestive differential binding to c.-101T>C but no binding to c.-215A>G. These data highlight the importance of in vitro testing of reported LDLR promoter variants to establish their role in FH. The functional assays performed suggest that the c.-101T>C and c.-121T>C variants are pathogenic, whereas c.-13A>G variant is benign, and the status of c.-215A>G remains unclear.European Journal of Human Genetics advance online publication, 24 September 2014; doi:10.1038/ejhg.2014.199