Contemporary perspective on addictive behaviors: underpinning mechanisms, assessment, and treatment

This special issue gathered contributions from authors in the scientifc community working on addictive behaviors. In particular, authors were solicited to relate about underpinning mechanisms, assessment protocols, and intervention programs that are currently proposed for substance abuse, Internet addiction, and other forms of problematic conducts in pediatric populations, adolescence, and adulthood. Most of the papers used a biopsychosocial model for the onset and maintaining of addictive behaviors and their comorbidities with other psychopathologies. Although the intent was accept contributions focused on all forms of addictive behaviors, this special issue is composed of four papers concerning problematic use of the web and two articles focusing on substance use. Of note, all papers addressed the developmental phases of childhood and adolescence

Uma abordagem fuzzy para a avaliação técnico-econômica de redes de acesso

The rising of new technologies and services imposes significant changes to the traditional telecommunications system. The diversity of system evolution settings makes the planning stage an increasingly desirable procedure, mainly in a competitive environment. The use of comprehensive and flexible methodologies that can support the decision process, based in optimization mathematical models, seems to be indispensable. This paper proposes a mixed-integer linear programming model devoted to help the strategic planning of the telecommunication systems, and in the special of the access network. Major components of costs and revenues are identified. The model intends to determine the network configuration (services, technologies, etc.) which maximizes the expected revenue. In order to perform some techno-economical risk analyses in situations with lack of precision in the demand data, fuzzy sets concepts are adopted. Results of computational experiments are presented and discussed.O surgimento de novas tecnologias e serviços vem impondo mudanças substanciais ao tradicional sistema de telecomunicações. Múltiplas possibilidades de evolução do sistema fazem da etapa de planejamento um procedimento não só desejável como necessário, principalmente num ambiente de competitividade. A utilização de metodologias abrangentes e flexíveis que possam auxiliar no processo de decisão, fundadas em modelos de otimização, parece um caminho inevitável. Este artigo propõe um modelo de programação linear inteiro misto para ajudar no planejamento estratégico de sistemas de telecomunicações, e em particular da rede de acesso. Os principais componentes de custo e receita são identificados e o modelo é desenvolvido para determinar a configuração da rede (serviços, tecnologias, etc) que maximize a receita esperada pelo operador do sistema. O conceito de números fuzzy é adotado para avaliar o risco técnico-econômico em situações de imprecisão nos dados de demanda. Resultados de experimentos computacionais são apresentados e discutidos.22624

Renormalized Path Integral for the Two-Dimensional Delta-Function Interaction

A path-integral approach for delta-function potentials is presented. Particular attention is paid to the two-dimensional case, which illustrates the realization of a quantum anomaly for a scale invariant problem in quantum mechanics. Our treatment is based on an infinite summation of perturbation theory that captures the nonperturbative nature of the delta-function bound state. The well-known singular character of the two-dimensional delta-function potential is dealt with by considering the renormalized path integral resulting from a variety of schemes: dimensional, momentum-cutoff, and real-space regularization. Moreover, compatibility of the bound-state and scattering sectors is shown.Comment: 26 pages. The paper was significantly expanded and numerous equations were added for the sake of clarity; the main results and conclusions are unchange

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Uma abordagem fuzzy para a avaliação técnico-econômica de redes de acesso

O surgimento de novas tecnologias e serviços vem impondo mudanças substanciais ao tradicional sistema de telecomunicações. Múltiplas possibilidades de evolução do sistema fazem da etapa de planejamento um procedimento não só desejável como necessário, principalmente num ambiente de competitividade. A utilização de metodologias abrangentes e flexíveis que possam auxiliar no processo de decisão, fundadas em modelos de otimização, parece um caminho inevitável. Este artigo propõe um modelo de programação linear inteiro misto para ajudar no planejamento estratégico de sistemas de telecomunicações, e em particular da rede de acesso. Os principais componentes de custo e receita são identificados e o modelo é desenvolvido para determinar a configuração da rede (serviços, tecnologias, etc) que maximize a receita esperada pelo operador do sistema. O conceito de números fuzzy é adotado para avaliar o risco técnico-econômico em situações de imprecisão nos dados de demanda. Resultados de experimentos computacionais são apresentados e discutidos.The rising of new technologies and services imposes significant changes to the traditional telecommunications system. The diversity of system evolution settings makes the planning stage an increasingly desirable procedure, mainly in a competitive environment. The use of comprehensive and flexible methodologies that can support the decision process, based in optimization mathematical models, seems to be indispensable. This paper proposes a mixed-integer linear programming model devoted to help the strategic planning of the telecommunication systems, and in the special of the access network. Major components of costs and revenues are identified. The model intends to determine the network configuration (services, technologies, etc.) which maximizes the expected revenue. In order to perform some techno-economical risk analyses in situations with lack of precision in the demand data, fuzzy sets concepts are adopted. Results of computational experiments are presented and discussed

Mutations in the gene encoding 3-hydroxyisobutyryl-CoA hydrolase results in progressive infantile neurodegeneration

Only a single patient with 3-hydroxyisobutyryl-CoA hydrolase deficiency has been described in the literature, and the molecular basis of this inborn error of valine catabolism has remained unknown until now. Here, we present a second patient with 3-hydroxyisobutyryl-CoA hydrolase deficiency, who was identified through blood spot acylcarnitine analysis showing persistently increased levels of hydroxy-C(4)-carnitine. Both patients manifested hypotonia, poor feeding, motor delay, and subsequent neurological regression in infancy. Additional features in the newly identified patient included episodes of ketoacidosis and Leigh-like changes in the basal ganglia on a magnetic resonance imaging scan. In cultured skin fibroblasts from both patients, the 3-hydroxyisobutyryl-CoA hydrolase activity was deficient, and virtually no 3-hydroxyisobutyryl-CoA hydrolase protein could be detected by western blotting. Molecular analysis in both patients uncovered mutations in the HIBCH gene, including one missense mutation in a conserved part of the protein and two mutations affecting splicing. A carefully interpreted acylcarnitine profile will allow more patients with 3-hydroxyisobutyryl-CoA hydrolase deficiency to be diagnose

Can acetylcysteine ameliorate cisplatin‐induced toxicities and oxidative stress without decreasing antitumor efficacy? A randomized, double‐blind, placebo‐controlled trial involving patients with head and neck cancer

Abstract The protective antioxidant activity of acetylcysteine (NAC) against toxicity due to cisplatin has been reported in experimental models; however, its efficacy in patients has not been elucidated. The aim of this study was to investigate the possible protective effect of NAC on cisplatin‐induced toxicity and the effect of NAC on clinical response and oxidative stress in patients treated for head and neck cancer. This was a randomized, double‐blind, placebo‐controlled trial conducted in patients receiving high‐dose cisplatin chemotherapy concomitant to radiotherapy. Patients were randomly assigned to groups and received: (a) 600 mg NAC syrup, orally once daily at night for 7 consecutive days or (b) placebo, administered similarly to NAC. Nephro‐, oto‐, hepato‐, myelo‐, and gastrointestinal toxicities, clinical responses, and plasma and cellular markers of oxidative stress were evaluated. Fifty‐seven patients were included (n = 28, NAC arm; and n = 29, placebo arm). A high prevalence of most types of toxicities was observed after cisplatin chemotherapy; however, the parameters were similar between the two groups. There was a predominance of partial response to treatment. In the cellular and plasmatic oxidative stress analyses, minor differences were observed. Overall, there was no statistically significant difference between the groups for all outcomes. These findings show that low‐dose oral NAC does not protect patients with head and neck cancer from cisplatin‐induced toxicities and oxidative stress. The antitumor efficacy of cisplatin was apparently not impaired by NAC

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons