Genetic Algorithm with Optimal Recombination for the Asymmetric Travelling Salesman Problem

We propose a new genetic algorithm with optimal recombination for the asymmetric instances of travelling salesman problem. The algorithm incorporates several new features that contribute to its effectiveness: (i) Optimal recombination problem is solved within crossover operator. (ii) A new mutation operator performs a random jump within 3-opt or 4-opt neighborhood. (iii) Greedy constructive heuristic of W.Zhang and 3-opt local search heuristic are used to generate the initial population. A computational experiment on TSPLIB instances shows that the proposed algorithm yields competitive results to other well-known memetic algorithms for asymmetric travelling salesman problem.Comment: Proc. of The 11th International Conference on Large-Scale Scientific Computations (LSSC-17), June 5 - 9, 2017, Sozopol, Bulgari

Does blood transfusion harm cardiac surgery patients?

Over recent years there has been a substantial body of evidence demonstrating strong associations between transfusion and adverse outcomes, including myocardial, neurological and renal injury, in a range of clinical settings where transfusion is administered for reasons other than life-threatening bleeding. The strength of these associations across a range of clinical settings suggests that confounding and bias, the chief limitations of all observational studies, are unlikely to account for all of these observations. Given the wide range in transfusion rates in cardiac centres, with up to 100% of patients in some centres exposed to allogenic blood components, this evidence, albeit circumstantial, presents a strong argument for prospective randomised trials to attempt to determine, firstly, if transfusion causes adverse outcomes, and secondly, in which patient groups does the benefit of transfusion outweigh these risks? These issues are discussed in the context of an article published this month in BMC Medicine

Use of functional feeding strategies to protect Atlantic salmon from virally-induced inflammatory diseases- mechanistic insights revealed by transcriptomic analysis

Over the past few years one of the major concerns in the Atlantic salmon (Salmo salar) farming industry has been the increasing incidence and severity of inflammatory viral diseases. Heart and skeletal muscle inflammation (HSMI) and cardiomyopathy syndrome (CMS) are currently two of the most prevalent viral diseases in commercial Atlantic salmon farms in Norway. Mortality levels in both diseases are generally low but morbidity can be very high with the associated chronic inflammatory response lasting for several months. The consequent reduced growth performance is causing considerable financial impact as HSMI has become increasingly widespread in recent years. The impact of CMS is further exacerbated as it generally affects large fish close to harvest. HSMI lesions occur in the atrium and ventricle in the heart including inflammation and necrosis in epi- endo- and myocardium along with myositis of red skeletal muscle. CMS lesions are commonly observed in the spongy myocardium in the atrium and ventricle of the heart with severe mononuclear inflammation and necrosis. Furthermore, circulatory disturbances associated with reduced cardiac function cause multifocal liver steatosis and necrosis in both diseases. Currently there are no vaccines or any other effective treatments for these diseases and so alternative therapies that could potentially modulate the intensity of the inflammatory response could be crucial to improve the clinical manifestation of the diseases. Therefore, the overall aim of the present study was to evaluate the concept of “clinical nutrition” to improve the clinical symptoms of both viral diseases, HSMI and CMS, through the use of functional feeds formulated with reduced lipid content and increased proportions of anti-inflammatory fatty acids to moderate the apparently uncontrolled inflammatory response in the heart tissue associated with both diseases and also alleviate the secondary hepatic lesions. The experimental work consisted of three major dietary trials in Atlantic salmon in seawater. Two large trials investigated the effects of functional feeds in Atlantic salmon challenged with Atlantic salmon piscine reovirus (ASRV) and piscine myocarditis virus (PMCV), the causal agents of HSMI and CMS, respectively. In both trials, heart transcriptome, heart and liver histopathology and tissue lipid and fatty acid compositions and metabolism were determined post-infection in fish fed with the functional feeds in comparison with fish fed with a standard commercial feed formulation considered as a reference diet. All the functional feeds were formulated to have reduced digestible energy through lower dietary lipid and higher protein contents, and increased levels and proportions of anti-inflammatory long-chain polyunsaturated fatty acids (LC-PUFA), particularly eicosapentaenoic acid (EPA) compared with the reference diets. Histopathology, fatty acid composition and gene expression of heart were assessed over a long time-period of 16 weeks and 14 weeks post-challenge with ASRV and PMCV, respectively. Viral load in heart tissue, hepatic histopathology and fatty acid composition of liver and head kidney along with expression of the genes involved in the eicosanoid and LC-PUFA and eicosanoid biosynthesis pathways were also determined in the HSMI trial. The third trial was a nutritional trial evaluating the effects of dietary digestible energy content on lipid and fatty acid metabolism in salmon fed diets containing graded amounts of lipid. Fatty acid composition of liver and heart were assessed over 12 weeks, along with the hepatic expression of genes of lipid and fatty acid metabolism. The results of this research are presented in four chapters (Chapters 2-5) as four paper manuscripts. The manuscripts/Papers are either published (Chapter 2), in review (Chapter 3 and 4) or drafted for submission (Chapter 5) in appropriate peer-reviewed international journals. Chapter 2 and 3 correspond to the HSMI trial, Chapter 4 to the nutritional trial, and Chapter 5 to the CMS trial. Chapter 2 showed that viral load and histopathology scores were lower in fish fed the functional feeds, especially diet FF1, which displayed better performance. Diet strongly influenced the expression of genes related with the immune and inflammatory responses, with delayed expression in fish fed the functional feeds. Up-regulation of pro-inflammatory genes was correlated with the higher viral load observed at early-mid stages of the disease in fish fed the reference diet (ST). Expression of genes related with the immune response at 16-weeks post challenge reflected the differences in immunomodulation between the functional feeds, with fish fed diet FF1 showing lower expression. Therefore, severity of the heart lesions was correlated with the intensity of the immune response and could be associated with tissue anti-inflammatory LC-PUFA levels. Chapter 3 was focused on liver histopathology, fatty acid composition and LC-PUFA biosynthesis, along with phospholipid fatty acid composition and eicosanoid production in head kidney and heart tissue at early and late stages of ASRV infection. Liver was severely affected by the virus at the beginning of the infection in fish fed the reference ST diet, but the level of lesions were similar in all dietary groups at the end of the trial. Hepatic expression of fatty acyl desaturases was significantly depressed in fish fed the ST diet compare with fish fed the functional feeds despite the lower levels of dietary LC-PUFA in that feed. Thus endogenous production and bioavailability of anti-inflammatory LC-PUFA was potentially enhanced in fish fed the functional feeds. Changes in tissue lipid content, mobilization of fatty acids involved in inflammatory responses and changes in expression of transcription factors and genes involved in eicosanoid biosynthesis were more prominent in head kidney, confirming the important role of this organ in dietary immunomodulation after viral infection. To a lesser extent similar changes were observed in heart tissue, suggesting in situ production of eicosanoids could also be important. The unexpected effects of diet on expression of genes of LC-PUFA biosynthesis were specifically investigated in the trial described in Chapter 4. One aim of this study was to clarify whether dietary lipid content or viral infection was the cause of altered expression of desaturase genes between the different diets. Hepatic expression of other genes of lipid and fatty acid metabolism were also determined to evaluate metabolic changes associated with dietary lipid/energy level. In general, reduction of dietary energy and lipid contents while maintaining similar proportions of dietary fatty acids, led to a general up-regulation of genes involved in lipid biosynthetic pathways. Thus salmon fed lower energy diet showed increased liver expression of fatty acyl desaturases in comparison with fish fed higher energy levels. Heart transcriptomic data in Chapter 5 showed a similar delay in the inflammatory response in fish fed the functional feeds after PCMV infection as observed in the HSMI study. Modulation of inflammatory responses, similar to that previously described after ASRV infection, was also observed in fish fed the functional feeds. However, the differences in the expression of immune related genes and the level of heart lesions were not as prominent at mid-late stages of the disease as in fish fed FF1 in the HSMI trial. The present study demonstrated the beneficial effects of a clinical nutrition approach via functional feeds in two viral inflammatory diseases, HSMI and CMS, currently affecting farmed Atlantic salmon. Dietary immunomodulation increased the availability of anti-inflammatory LC-PUFA and significantly influenced the expression of the genes related with the immune/inflammatory response reducing the level and severity of cardiac and liver lesions and therefore improving the performance of fish suffering the diseases

Isokinetic eccentric exercise substantially improves mobility, muscle strength and size, but not postural sway metrics in older adults, with limited regression observed following a detraining period

© 2020, The Author(s). Introduction: Eccentric exercise can reverse age-related decreases in muscle strength and mass; however, no data exist describing its effects on postural sway. As the ankle may be more important for postural sway than hip and knee joints, and with older adults prone to periods of inactivity, the effects of two 6-week seated isokinetic eccentric exercise programmes, and an 8-week detraining period, were examined in 27 older adults (67.1 ± 6.0 years). Methods: Neuromuscular parameters were measured before and after training and detraining periods with subjects assigned to ECC (twice-weekly eccentric-only hip and knee extensor contractions) or ECCPF (identical training with additional eccentric-only plantarflexor contractions) training programmes. Results: Significant (P \u3c 0.05) increases in mobility (decreased timed-up-and-go time [− 7.7 to − 12.0%]), eccentric strength (39.4–58.8%) and vastus lateralis thickness (9.8–9.9%) occurred after both training programmes, with low-to-moderate weekly rate of perceived exertion (3.3–4.5/10) reported. No significant change in any postural sway metric occurred after either training programme. After 8 weeks of detraining, mobility (− 8.2 to − 11.3%), eccentric strength (30.5–50.4%) and vastus lateralis thickness (6.1–7.1%) remained significantly greater than baseline in both groups. Conclusion: Despite improvements in functional mobility, muscle strength and size, lower-limb eccentric training targeting hip, knee and ankle extensor muscle groups was not sufficient to influence static balance. Nonetheless, as the beneficial functional and structural adaptations were largely maintained through an 8-week detraining period, these findings have important implications for clinical exercise prescription as the exercise modality, low perceived training intensity, and adaptive profile are well suited to the needs of older adults

Sample size calculation for microarray experiments with blocked one-way design

<p>Abstract</p> <p>Background</p> <p>One of the main objectives of microarray analysis is to identify differentially expressed genes for different types of cells or treatments. Many statistical methods have been proposed to assess the treatment effects in microarray experiments.</p> <p>Results</p> <p>In this paper, we consider discovery of the genes that are differentially expressed among <it>K </it>(> 2) treatments when each set of <it>K </it>arrays consists of a block. In this case, the array data among <it>K </it>treatments tend to be correlated because of block effect. We propose to use the blocked one-way ANOVA <it>F</it>-statistic to test if each gene is differentially expressed among <it>K </it>treatments. The marginal p-values are calculated using a permutation method accounting for the block effect, adjusting for the multiplicity of the testing procedure by controlling the false discovery rate (FDR). We propose a sample size calculation method for microarray experiments with a blocked one-way design. With FDR level and effect sizes of genes specified, our formula provides a sample size for a given number of true discoveries.</p> <p>Conclusion</p> <p>The calculated sample size is shown via simulations to provide an accurate number of true discoveries while controlling the FDR at the desired level.</p

Hospital variation in transfusion and infection after cardiac surgery: a cohort study

<p>Abstract</p> <p>Background</p> <p>Transfusion practices in hospitalised patients are being re-evaluated, in part due to studies indicating adverse effects in patients receiving large quantities of stored blood. Concomitant with this re-examination have been reports showing variability in the use of specific blood components. This investigation was designed to assess hospital variation in blood use and outcomes in cardiac surgery patients.</p> <p>Methods</p> <p>We evaluated outcomes in 24,789 Medicare beneficiaries in the state of Michigan, USA who received coronary artery bypass graft surgery from 2003 to 2006. Using a cohort design, patients were followed from hospital admission to assess transfusions, in-hospital infection and mortality, as well as hospital readmission and mortality 30 days after discharge. Multilevel mixed-effects logistic regression was used to calculate the intrahospital correlation coefficient (for 40 hospitals) and compare outcomes by transfusion status.</p> <p>Results</p> <p>Overall, 30% (95 CI, 20% to 42%) of the variance in transfusion practices was attributable to hospital site. Allogeneic blood use by hospital ranged from 72.5% to 100% in women and 49.7% to 100% in men. Allogeneic, but not autologous, blood transfusion increased the odds of in-hospital infection 2.0-fold (95% CI 1.6 to 2.5), in-hospital mortality 4.7-fold (95% CI 2.4 to 9.2), 30-day readmission 1.4-fold (95% CI 1.2 to 1.6), and 30-day mortality 2.9-fold (95% CI 1.4 to 6.0) in elective surgeries. Allogeneic transfusion was associated with infections of the genitourinary system, respiratory tract, bloodstream, digestive tract and skin, as well as infection with <it>Clostridium difficile</it>. For each 1% increase in hospital transfusion rates, there was a 0.13% increase in predicted infection rates.</p> <p>Conclusion</p> <p>Allogeneic blood transfusion was associated with an increased risk of infection at multiple sites, suggesting a system-wide immune response. Hospital variation in transfusion practices after coronary artery bypass grafting was considerable, indicating that quality efforts may be able to influence practice and improve outcomes.</p

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration