Optimal softening for force calculations in collisionless N-body simulations

In N-body simulations the force calculated between particles representing a given mass distribution is usually softened, to diminish the effect of graininess. In this paper we study the effect of such a smoothing, with the aim of finding an optimal value of the softening parameter. As already shown by Merritt (1996), for too small a softening the estimates of the forces will be too noisy, while for too large a softening the force estimates are systematically misrepresented. In between there is an optimal softening, for which the forces in the configuration approach best the true forces. The value of this optimal softening depends both on the mass distribution and on the number of particles used to represent it. For higher number of particles the optimal softening is smaller. More concentrated mass distributions necessitate smaller softening, but the softened forces are never as good an approximation of the true forces as for not centrally concentrated configurations. We give good estimates of the optimal softening for homogeneous spheres, Plummer spheres, and Dehnen spheres. We also give a rough estimate of this quantity for other mass distributions, based on the harmonic mean distance to the $k$th neighbour ($k$ = 1, .., 12), the mean being taken over all particles in the configuration. Comparing homogeneous Ferrers ellipsoids of different shapes we show that the axial ratios do not influence the value of the optimal softening. Finally we compare two different types of softening, a spline softening (Hernquist & Katz 1989) and a generalisation of the standard Plummer softening to higher values of the exponent. We find that the spline softening fares roughly as well as the higher powers of the power-law softening and both give a better representation of the forces than the standard Plummer softening.Comment: 16 pages Latex, 19 figures, accepted for publication in MNRAS, corrected typos, minor changes mainly in sec.

The role of forest genetic resources in responding to biotic and abiotic factors in the context of anthropogenic climate change

The current distribution of forest genetic resources on Earth is the result of a combination of natural processes and human actions. Over time, tree populations have become adapted to their habitats including the local ecological disturbances they face. As the planet enters a phase of human-induced climate change of unprecedented speed and magnitude, however, previously locally-adapted populations are rendered less suitable for new conditions, and ‘natural’ biotic and abiotic disturbances are taken outside their historic distribution, frequency and intensity ranges. Tree populations rely on phenotypic plasticity to survive in extant locations, on genetic adaptation to modify their local phenotypic optimum or on migration to new suitable environmental conditions. The rate of required change, however, may outpace the ability to respond, and tree species and populations may become locally extinct after specific, but as yet unknown and unquantified, tipping points are reached. Here, we review the importance of forest genetic resources as a source of evolutionary potential for adaptation to changes in climate and other ecological factors. We particularly consider climate-related responses in the context of linkages to disturbances such as pests, diseases and fire, and associated feedback loops. The importance of management strategies to conserve evolutionary potential is emphasised and recommendations for policy-makers are provided

Detecting short spatial scale local adaptation and epistatic selection in climate-related candidate genes in European beech (Fagus sylvatica) populations

Detecting signatures of selection in tree populations threatened by climate change is currently a major research priority. Here, we investigated the signature of local adaptation over a short spatial scale using 96 European beech (Fagus sylvatica L.) individuals originating from two pairs of populations on the northern and southern slopes of Mont Ventoux (south-eastern France). We performed both single and multi-locus analysis of selection based on 53 climate-related candidate genes containing 546 SNPs. FST outlier methods at the SNP level revealed a weak signal of selection, with three marginally significant outliers in the northern populations. At the gene-level, considering haplotypes as alleles, two additional marginally significant outliers were detected, one on each slope. To account for the uncertainty of haplotype inference, we averaged the Bayes Factors over many possible phase reconstructions. Epistatic selection offers a realistic multi-locus model of selection in natural populations. Here, we used a test suggested by Ohta based on the decomposition of the variance of linkage disequilibrium. Over all populations, 0.23% of the SNP pairs (haplotypes) showed evidence of epistatic selection, with nearly 80% of them being within genes. One of the between gene epistatic selection signals arose between an FST outlier and a non-synonymous mutation in a drought response gene. Additionally, we identified haplotypes containing selectively advantageous allele combinations which were unique to high or low-elevations and northern or southern populations. Several haplotypes contained non-synonymous mutations situated in genes with known functional importance for adaptation to climatic factor

How common is truly benign MS in a UK population?

Objectives The prevalence and definition of benign multiple sclerosis (BMS) remain controversial. Most definitions are based on the Expanded Disability Status Scale (EDSS), not encompassing the wider impact of disease. The explanation for favourable outcomes remains unclear. We aim to provide a detailed characterisation of patients with low EDSS scores at long disease durations. Methods We screened a population-based registry containing 3062 people with MS to identify individuals with unlimited walking ability at disease durations >15 years. A representative cohort underwent detailed clinical assessment and classified as having BMS according to EDSS score <3, no significant fatigue, mood disturbance, cognitive impairment or disrupted employment, and had not received a disease-modifying therapy. We determined patient-reported perceptions of MS status and made comparisons with EDSS-based definitions. Results Of 1049 patients with disease duration of >15 years, 200 (19.1%) had most recent EDSS score <4.0. Detailed contemporary clinical assessment of a representative sample of 60 of these patients revealed 48 (80%) had an EDSS score of <4.0, 35 (58%) <3.0 and 16 (27%) <2.0. Only nine (15%) fulfilled our criteria for BMS; impaired cognition (57%) and effects on employment (52%) the most common causes for exclusion. Meanwhile, 33/60 (69%) patients considered their disease benign. Population frequency for BMS was estimated at 2.9% (95% CI 2.0 to 4.1). Conclusions Comprehensive assessment reveals a small minority of people with MS who appear genuinely benign after 15 years. Study of such individuals may uncover insights about disease pathogenesis. However, discrepancy between patient perception and clinician perception of BMS undermines use of the term ‘benign’ in clinical settings

Forest genetic resources strategy for Europe

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Straightforward access to chalcogenoureas derived from N-heterocyclic carbenes and their coordination chemistry

Chalcogen-based urea compounds supported by a wide range of N-heterocyclic carbenes are synthesised and fully characterised. Coordination of selenoureas is further explored with Group 11 transition metals to form new copper, gold and silver complexes. Single crystal X-ray analyses unambiguously establish the solid-state coordination of these complexes and show that the geometry of a complex is highly influenced by a combination of electronic properties – mainly π-accepting ability – and steric hindrance of the ligands, as well as the nature of the metal, affording a variety of coordination behaviours. In this report, we investigate these phenomena using several experimental methods

Levator anguli oris muscle based flaps for nasal reconstruction following resection of nasal skin tumours

<p>Abstract</p> <p>Background</p> <p>surgical excision remains the best tool for management of skin tumors affecting nasal skin, however many surgical techniques have been used for reconstruction of the nasal defects caused by excisional surgery. The aim of this work is the evaluation of the feasibility and outcome of levator anguli oris muscle based flaps.</p> <p>Methods</p> <p>Ninety patients of malignant nasal skin tumours were included in this study. Age was ranged from four to 78 years. For small unilateral defects affecting only one side ala nasi, levator anguli oris myocautaneous (LAOMC) flap was used in 45 patients. For unilateral compound loss of skin and mucus membrane, levator anguli oris myocautaneous mucosal (LAOMCM) flap was used in 23 patients. Very large defects; bilateral either LAOMC or LAOMCM flaps combined with forehead glabellar flaps were used to reconstruct the defect in 22 patients.</p> <p>Results</p> <p>Wound dehiscence was the commonest complication. Minor complications, in the form of haematoma and minor flap loss were managed conservatively. Partial flap loss was encountered in 6 patients with relatively larger tumours or diabetic co-morbidity, three of whom were required operative re-intervention in the form of debridement and flap refashioning, while total flap loss was not occurred at all.</p> <p>Conclusions</p> <p>Immediate nasal reconstruction for nasal skin and mucosal tumours with levator anguli oris muscle based flaps (LAOMC, LAOMCM) is feasible and spares the patient the psychic trauma due to organ loss.</p

Smooth Muscle Myosin Inhibition: A Novel Therapeutic Approach for Pulmonary Hypertension

Pulmonary hypertension remains a major clinical problem despite current therapies. In this study, we examine for the first time a novel pharmacological target, smooth muscle myosin, and determine if the smooth muscle myosin inhibitor, CK-2019165 (CK-165) ameliorates pulmonary hypertension.Six domestic female pigs were surgically instrumented to measure pulmonary blood flow and systemic and pulmonary vascular dynamics. Pulmonary hypertension was induced by hypoxia, or infusion of the thromboxane analog (U-46619, 0.1 µg/kg/min, i.v.). In rats, chronic pulmonary hypertension was induced by monocrotaline.CK-165 (4 mg/kg, i.v.) reduced pulmonary vascular resistance by 22±3 and 28±6% from baseline in hypoxia and thromboxane pig models, respectively (p<0.01 and 0.01), while mean arterial pressure also fell and heart rate rose slightly. When CK-165 was delivered via inhalation in the hypoxia model, pulmonary vascular resistance fell by 17±6% (p<0.05) while mean arterial pressure and heart rate were unchanged. In the monocrotaline model of chronic pulmonary hypertension, inhaled CK-165 resulted in a similar (18.0±3.8%) reduction in right ventricular systolic pressure as compared with sildenafil (20.3±4.5%).Inhibition of smooth muscle myosin may be a novel therapeutic target for treatment of pulmonary hypertension

Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma

Background: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. Objective: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. Design, setting, and participants: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). Outcome measurements and statistical analysis: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. Results and limitations: Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38-5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08-2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03-0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20-7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era. Conclusions: Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients. Patient summary: We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications