A population-based stochastic coordinate descent method

This paper addresses the problem of solving a bound constrained global optimization problem by a population-based stochastic coordinate descent method. To improve efficiency, a small subpopulation of points is randomly selected from the original population, at each iteration. The coordinate descent directions are based on the gradient computed at a special point of the subpopulation. This point could be the best point, the center point or the point with highest score. Preliminary numerical experiments are carried out to compare the performance of the tested variants. Based on the results obtained with the selected problems, we may conclude that the variants based on the point with highest score are more robust and the variants based on the best point less robust, although they win on efficiency but only for the simpler and easy to solve problems.This work has been supported by FCT – Fundação para a Ciência e Tecnologia within the Projects Scope: UID/CEC/00319/2019 and UID/MAT/00013/2013

Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between <it>H. pylori </it>CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis.</p> <p>Results</p> <p>The number of EPIYA C segments was significantly associated with the increased risk of gastric carcinoma (OR = 3.08, 95% CI = 1.74 to 5.45, p < 10^-3) even after adjustment for age and gender. Higher number of EPIYA C segments was also associated with gastric atrophy (p = 0.04) and intestinal metaplasia (p = 0.007). Furthermore, patients infected by <it>cag</it>A strains possessing more than one EPIYA C segment showed decreased serum levels of pepsinogen I in comparison with those infected by strains containing one or less EPIYA C repeat. Otherwise, the number of EPIYA C segments did not associate with duodenal ulcer.</p> <p>Conclusions</p> <p>Our results demonstrate that infection with <it>H. pylori </it>strains harbouring more than one CagA EPIYA C motif was clearly associated with gastric cancer, but not with duodenal ulcer.</p> <p>Higher number of EPIYA C segments was also associated with gastric precancerous lesions as demonstrated by histological gastric atrophic and metaplastic changes and decreased serum levels of pepsinogen I.</p

Very special relativity as relativity of dark matter: the Elko connection

In the very special relativity (VSR) proposal by Cohen and Glashow, it was pointed out that invariance under HOM(2) is both necessary and sufficient to explain the null result of the Michelson-Morely experiment. It is the quantum field theoretic demand of locality, or the requirement of P, T, CP, or CT invariance, that makes invariance under the Lorentz group a necessity. Originally it was conjectured that VSR operates at the Planck scale; we propose that the natural arena for VSR is at energies similar to the standard model, but in the dark sector. To this end we provide an ab initio spinor representation invariant under the SIM(2) avatar of VSR and construct a mass dimension one fermionic quantum field of spin one half. This field turns out to be a very close sibling of Elko and it exhibits the same striking property of intrinsic darkness with respect to the standard model fields. In the new construct, the tension between Elko and Lorentz symmetries is fully resolved. We thus entertain the possibility that the symmetries underlying the standard model matter and gauge fields are those of Lorentz, while the event space underlying the dark matter and the dark gauge fields supports the algebraic structure underlying VSR.Comment: 19 pages. Section 5 is new. Published version (modulo a footnote, and a corrected typo

Tilt Training Increases Vasoconstrictor Reserve in Patients with Neurocardiogenic Syncope

A síncope neurocardiogénica (SNc) é uma entidade clínica comum, resultante de uma resposta autonómica reflexa excessiva durante o stress ortostático. As diferentes opções terapêuticas são controversas e de eficácia limitada. O treino de ortostatismo (TTr) tem-se mostrado uma alternativa prometedora no tratamento destes doentes (D). No entanto, permanece por esclarecer o seu mecanismo de acção e o impacto clínico numa população com SNc recorrente. Objectivo: Caracterizar a resposta hemodinâmica e autonómica durante um programa de TTr em doentes com SNc refratária às medidas convencionais. População e métodos: Foram estudados 28D (50% do sexo masculino, 41±14 anos), sem evidência de cardiopatia, com SNc documentada em teste de ortostatismo passivo. O TTr incluiu 9 sessões hospitalares (3x/semana, 30 minutos) com monitorizac¸ão contínua de pressão arterial e frequência cardíaca (60◦ - 6 sessões - 70◦ - 3 sessões), complementadas com treino diário no domicílio e elevação da cabeceira a 10◦ durante o sono. O volume sistólico, o débito cardíaco, a resistência vascular periférica, a sensibilidade do barorreflexo e a variabilidade da frequência cardíaca foram calculados. Todos os doentes foram reavaliados no fim do 1.◦ mês e no final de cada 6 meses num período máximo de 36 meses (follow-up 24±12 meses). Resultados: Ao longo das sessões de TTr verificou-se um aumento significativo e consistente da resistência total periférica (1485±225 vs. 1591±187 dyne*s/cm−5, p < 0,05) associado a uma diminuição do seu desvio-padrão (206±60 vs. 150±42, p < 0,05). Durante o período de follow-up, houve recorrência de síncope em 5D (19%), com redução significativa do número de síncopes (4,0±3,2/D nos 12 meses pre-TTr vs. 1,4±0,8/D pos-TTr, p < 0,05). Conclusão: Em doentes com SNc refratária, o TTr mostrou ser uma opção terapêutica eficaz, com benefício a longo prazo. A melhor tolerância ao ortostatismo parece resultar do aumento da reserva vasoconstritora e da sua menor variabilidade

O Treino de Ortostatismo (Tilt Training) Aumenta a Reserva Vasoconstritora em Doentes com Síncope Reflexa Neurocardiogénica

Neurocardiogenic syncope (NCS) is a common clinical entity resulting from an excessive reflex autonomic response, particularly during orthostatism. Treatment options are controversial and of limited effectiveness. Tilt training (TT) is a promising option to treat these patients. However, its mechanism of action and clinical impact remain unclear. OBJECTIVE: To characterize hemodynamic and autonomic responses during a TT program in patients with NCS refractory to conventional measures. METHODS: We studied 28 patients (50% male, mean age 41±14 years) without structural heart disease, with NCS documented by tilt testing. The TT program included 9 tilt sessions (3 times a week, 30 min) (60° - 6 sessions, 70° - 3 sessions), under ECG and blood pressure monitoring combined with home orthostatic self-training and 10° head-up during sleep. Systolic volume, cardiac output, total peripheral resistance, baroreflex sensitivity and heart-rate variability were computed. Patients were reassessed at 1 month and every 6 months for a maximum of 36 months (24±12 months). RESULTS: Over the course of the TT program there was a significant increase in total peripheral resistance (1485±225 vs. 1591±187 dyn·s·cm(-5), p<0.05), with a decrease in standard deviation (206±60 vs. 150±42, p<0.05). During follow-up, syncope recurred in five patients (19%), with a significant reduction in the number of episodes (4.0±3.2/patient in the 12 months before TT vs. 1.4±0.8/patient post-TT, p<0.05). CONCLUSION: In refractory NCS, TT may be an effective therapeutic option, with long-term benefits. These results appear to be due to an increase in vasoconstrictor reserve combined with a reduction in its variance

Dengue disease surveillance: an updated systematic literature review

Objectives To review the evidence for the application of tools for dengue outbreak prediction/detection and trend monitoring in passive and active disease surveillance systems in order to develop recommendations for endemic countries and identify important research needs. Methods This systematic literature review followed the protocol of a review from 2008, extending the systematic search from January 2007 to February 2013 on PubMed, EMBASE, CDSR, WHOLIS and Lilacs. Data reporting followed the PRISMA statement. The eligibility criteria comprised (i) population at risk of dengue, (ii) dengue disease surveillance, (iii) outcome of surveillance described and (iv) empirical data evaluated. The analysis classified studies based on the purpose of the surveillance programme. The main limitation of the review was expected publication bias. Results A total of 1116 papers were identified of which 36 articles were included in the review. Four cohort-based prospective studies calculated expansion factors demonstrating remarkable levels of underreporting in the surveillance systems. Several studies demonstrated that enhancement methods such as laboratory support, sentinel-based reporting and staff motivation contributed to improvements in dengue reporting. Additional improvements for passive surveillance systems are possible by incorporating simple data forms/entry/electronic-based reporting; defining clear system objectives; performing data analysis at the lowest possible level (e.g. district); seeking regular data feedback. Six studies showed that serotype changes were positively correlated with the number of reported cases or with dengue incidence, with lag times of up to 6 months. Three studies found that data on internet searches and event-based surveillance correlated well with the epidemic curve derived from surveillance data. Conclusions Passive surveillance providing the baseline for outbreak alert should be strengthened and appropriate threshold levels for outbreak alerts investigated. Additional enhancement tools such as syndromic surveillance, laboratory support and motivation strategies can be added. Appropriate alert signals need to be identified and integrated into a risk assessment tool. Shifts in dengue serotypes/genotype or electronic event-based surveillance have also considerable potential as indicator in dengue surveillance. Further research on evidence-based response strategies and cost-effectiveness is needed

Studies on the antimicrobial activity and brine shrimp toxicity of Zeyheria tuberculosa (Vell.) Bur. (Bignoniaceae) extracts and their main constituents

<p>Abstract</p> <p>Background</p> <p>Due to the indiscriminate use of antimicrobial drugs, the emergence of human pathogenic microorganisms resistant to major classes of antibiotics has been increased and has caused many clinical problems in the treatment of infectious diseases. Thus, the aim of this study was to evaluate for the first time the <it>in vitro </it>antimicrobial activity and brine shrimp lethality of extracts and isolated compounds from <it>Zeyheria tuberculosa </it>(Vell.) Bur., a species used in Brazilian folk medicine for treatment of cancer and skin diseases.</p> <p>Methods</p> <p>Using the disc diffusion method, bioautography assay and brine shrimp toxicity test (<it>Artemia salina </it>Leach), we studied the antimicrobial activity and lethality of extracts and isolated compounds against three microorganisms strains, including Gram-positive (<it>Staphylococcus aureus</it>) and Gram-negative (<it>Pseudomonas aeruginosa</it>) bacteria and yeasts (<it>Candida albicans</it>).</p> <p>Results</p> <p>In this study, the extracts inhibited <it>S. aureus </it>(8.0 ± 0.0 to 14.0 ± 0.0 mm) and <it>C. albicans </it>(15.3 ± 0.68 to 25.6 ± 0.4 mm) growth. In the brine shrimp test, only two of them showed toxic effects (LC₅₀29.55 to 398.05 μg/mL) and some extracts were non-toxic or showed weak lethality (LC₅₀705.02 to > 1000 μg/mL). From these extracts, four flavones [5,6,7,8-tetramethoxyflavone (1), 5,6,7-trimethoxyflavone (2), 4'-hydroxy-5,6,7,8-tetramethoxyflavone (3), and 4'-hydroxy-5,6,7-trimethoxyflavone (4)] were isolated through bioassay-guided fractionation and identified based on the 1D and 2D NMR spectral data. By bioautography assays, compounds 1 [<it>S. aureus </it>(16.0 ± 0.0 mm) and <it>C. albicans </it>(20.0 ± 0.0 mm)] and 3 [<it>S. aureus </it>(10.3 ± 0.6 mm) and <it>C. albicans </it>(19.7 ± 0.6 mm)] inhibited both microorganisms while 2 inhibited only <it>S. aureus </it>(11.7 ± 0.6 mm). Compound 4 did not restrain the growth of any tested microorganism.</p> <p>Conclusion</p> <p>Our results showed that extracts and isolated flavones from <it>Z. tuberculosa </it>may be particularly useful against two pathogenic microorganisms, <it>S. aureus </it>and <it>C. albicans</it>. These results may justify the popular use this species since some fractions tested had antimicrobial activity and others showed significant toxic effects on brine shrimps. However, in order to evaluate possible clinical application in therapy of infectious diseases, further studies about the safety and toxicity of isolated compounds are needed.</p

Effects of Vagal Stimulation on Induction and Termination of Atrial Fibrillation in an in Vivo Rabbit Heart Model

INTRODUCTION: Vagal activity is thought to influence atrial electrophysiological properties and play a role in the initiation and maintenance of atrial fibrillation (AF). In this study, we assessed the effects of acute vagal stimulation (vagus_stim) on atrial conduction times, atrial and pulmonary vein (PV) refractoriness, and vulnerability to induction of AF in the rabbit heart with intact autonomic innervation. METHODS: An open-chest epicardial approach was performed in 11 rabbits (New Zealand; 3.9-5.0 kg), anesthetized and artificially ventilated after neuromuscular blockade. A 3-lead ECG was obtained. Atrial electrograms were recorded along the atria, from right to left (four monopolar electrodes), together with a circular electrode adapted for proximal left PV assessment. Acute vagus nerve stimulation was obtained with bipolar electrodes (20 Hz). Epicardial activation was recorded in sinus rhythm, and the conduction time from right (RA) to left atrium (LA), and from RA to PVs, was measured in basal conditions and during vagus_stim. The atrial effective refractory period (ERP) and dispersion of refractoriness (Disp_A) were analyzed. Vulnerability to AF induction was assessed at the right (RAA) and left (LAA) atrial appendages and the PVs. Atrial stimulation (50 Hz) was performed alone or combined with vagus_stim. Heart rate and blood pressure were monitored. RESULTS: In basal conditions, there was a significant delay in conduction from RA to PVs, not influenced by vagus_stim, and the PV ERPs were shorter than those measured in LA and LAA, but without significant differences compared to RA and RAA. During vagus_stim, conduction times between RA and LA increased from 16+8 ms to 27+6 ms (p 10 s in 45.4% of rabbits during vagus_stim, and ceased after vagus_stim in 4 out of these 5 cases. In 3 animals, PV tachycardia, with fibrillatory conduction, induced with 50 Hz PV pacing during vagus_stim. CONCLUSIONS: Vagus_stim reduces interatrial conduction velocity and significantly shortens atrial ERP, contributing to the induction and duration of AF episodes in the in vivo rabbit heart. This model may be useful for the assessment of autonomic influence on the pathophysiology of AF

Effects of Acute Autonomic Modulation on Atrial Conduction Delay and Local Electrograms Duration in Paroxysmal Atrial Fibrillation

Slowed atrial conduction may contribute to reentry circuits and vulnerability for atrial fibrillation (AF). The autonomic nervous system (ANS) has modulating effects on electrophysiological properties. However, complex interactions of the ANS with the arrhythmogenic substrate make it difficult to understand the mechanisms underlying induction and maintenance of AF. AIM: To determine the effect of acute ANS modulation in atrial activation times in patients (P) with paroxysmal AF (PAF). METHODS AND RESULTS: 16P (9 men; 59±14years) with PAF, who underwent electrophysiological study before AF ablation, and 15P (7 men; 58±11years) with atrioventricular nodal reentry tachycardia, without documentation or induction of AF (control group). Each group included 7P with arterial hypertension but without underlying structural heart disease. The study was performed while off drugs. Multipolar catheters were placed at the high right atrium (HRA), right atrial appendage (RAA), coronary sinus (CS) and His bundle area (His). At baseline and with HRA pacing (600ms, shortest propagated S2) we measured: i) intra-atrial conduction time (IACT, between RAA and atrial deflection in the distal His), ii) inter-atrial conduction time (interACT, between RAA and distal CS), iii) left atrial activation time (LAAT, between atrial deflection in the distal His and distal CS), iv) bipolar electrogram duration at four atrial sites (RAA, His, proximal and distal CS). In the PAF group, measurements were also determined during handgrip and carotid sinus massage (CSM), and after pharmacological blockade of the ANS (ANSB). AF was induced by HRA programmed stimulation in 56% (self-limited - 6; sustained - 3), 68.8% (self-limited - 6; sustained - 5), and 50% (self-limited - 5; sustained - 3) of the P, in basal, during ANS maneuvers, and after ANSB, respectively (p=NS). IACT, interACT and LAAT significantly lengthened during HRA pacing in both groups (600ms, S2). P with PAF have longer IACT (p<0.05), a higher increase in both IACT, interACT (p<0.01) and electrograms duration (p<0.05) with S2, and more fragmented activity, compared with the control group. Atrial conduction times and electrograms duration were not significantly changed during ANS stimulation. Nevertheless, ANS maneuvers increased heterogeneity of the local electrograms duration. Also, P with sustained AF showed longer interACT and LAAT during CSM. CONCLUSION: Atrial conduction times, electrograms duration and fractionated activity are increased in PAF, suggesting a role for conduction delays in the arrhythmogenic substrate. Acute vagal stimulation is associated with prolonged interACT and LAAT in P with inducible sustained AF and ANS modulation may influence the heterogeneity of atrial electrograms duration