Substance use and depression. Comparative course in adolescents.

OBJECTIVE: To examine the relation between depression and substance use in adolescents and the concomitant courses of both disorders. METHODS: Four individual interviews were administered to 85 adolescent substance users aged 14-19 years (mean 17.1 years, SD 1.4) over a 3.5 year period using the Adolescent Drug Abuse Interview (ADAD) and the Beck Depression Inventory (BDI-13). RESULTS: No predictive effect was observed on one dimension over the other, but each dimension was predictive of its own course. A decrease in substance-use severity paralleled a decrease in depressive state. Similarly, stable substance-use rates, either at a low or a high level, tended to be associated with low or high levels of depression, respectively. However, an increase in substance use was not accompanied by an increase in depressive states. Moreover, depression varied greatly between adolescents, and according to gender and age. CONCLUSIONS: Depressive states and substance use in adolescents can vary considerably overtime, and are closely but rather synchronically related. Since most of the adolescents do not seek help for substance-related problems, substance use should be systematically assessed in adolescents presenting with a depressive state.

Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of cancer-related venous thromboembolism.

Although extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was 149,865 dollars/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of 15,329 dollars. Overall, 46% (7108 dollars) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of 7,609 dollars. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin.

Biologia do triatoma vitticeps (Stal, 1859) em condiçoes de laboratórios (Hemiptera: Reduvidae: Triatominae) I. Ciclo evolutivo

Foram feitas observações do ciclo evolutivo do Triatoma vitticeps com alimentação semanal em camundongo, em condições de laboratório. De quatro casais virgens obtiveram-se 435 ovos, sendo que 149 destinaram-se ao ciclo evolutivo e 286 ao estudo da resistência ao jejum, o que constituirá a segunda etapa deste trabalho. Apenas 50 exemplares atingiram a fase adulta num período X (S) = 270 ± 45 dias. Quanto ao tempo de incubação, o 1° e o 2° estádios foram realizados, cada um, em menos de um mês, enquanto que os 3º, 4º e 5º estádios requereram cerca de um, dois e três meses, respectivamente. A procura pelo 1º repasto ocorreu de forma sensível no 3º, 6º e 10º dias. Em todos os estádios, mais de 50% dos exemplares realizaram apenas um repasto, com exceção do 5º, onde foram necessários dois. No que diz respeito ao intervalo de tempo entre o oferecimento do repasto, o ato de picar, e a duração do repasto, observou-se que estes aumentaram gradativamente de acordo com o estádio. Dos 423 repastos realizados, 390 não foram seguidos de defecação no prazo de 10 min. Sob este aspecto parece que o T. vitticeps não é um bom transmissor do T. cruzi. O experimento teve a duração de 13 meses e neste período as temperaturas máximas e mínimas e a umidade relativa do ar variaram em média de 28 ± 2°C a 25 ± 2°C e 80 ± 2%, respectivamente. O material é proveniente da criação mantida no Departamento de entomologia do Instituto Oswaldo Cruz.

Direct binding of peptides to MHC class I molecules on living cells. Analysis at the single cell level.

To directly assess the binding of exogenous peptides to cell surface-associated MHC class I molecules at the single cell level, we examined the possibility of combining the use of biotinylated peptide derivatives with an immunofluorescence detection system based on flow cytometry. Various biotinylated derivatives of the adenovirus 5 early region 1A peptide 234-243, an antigenic peptide recognized by CTL in the context of H-2Db, were first screened in functional assays for their ability to bind efficiently to Db molecules on living cells. Suitable peptide derivatives were then tested for their ability to generate positive fluorescence signals upon addition of phycoerythrin-labeled streptavidin to peptide derivative-bearing cells. Strong fluorescent staining of Db-expressing cells was achieved after incubation with a peptide derivative containing a biotin group at the C-terminus. Competition experiments using the unmodified parental peptide as well as unrelated peptides known to bind to Kd, Kb, or Db, respectively, established that binding of the biotinylated peptide to living cells was Db-specific. By using Con A blasts derived from different H-2 congenic mouse strains, it could be shown that the biotinylated peptide bound only to Db among > 20 class I alleles tested. Moreover, binding of the biotinylated peptide to cells expressing the Dbm13 and Dbm14 mutant molecules was drastically reduced compared to Db. Binding of the biotinylated peptide to freshly isolated Db+ cells was readily detectable, allowing direct assessment of the relative amount of peptide bound to distinct lymphocyte subpopulations by three-color flow cytometry. While minor differences between peripheral T and B cells could be documented, thymocytes were found to differ widely in their peptide binding activity. In all cases, these differences correlated positively with the differential expression of Db at the cell surface. Finally, kinetic studies at different temperatures strongly suggested that the biotinylated peptide first associated with Db molecules available constitutively at the cell surface and then with newly arrived Db molecules.

Ventricular arrhythmia in coronary artery disease: limits of a risk stratification strategy based on the ejection fraction alone and impact of infarct localization.

AIMS: Estimates of the left ventricular ejection fraction (LVEF) in patients with life-threatening ventricular arrhythmias related to coronary artery disease (CAD) have rarely been reported despite it has become the basis for determining patient's eligibility for prophylactic defibrillator. We aimed to determine the extent and distribution of reduced LVEF in patients with sustained ventricular tachycardia or ventricular fibrillation. METHODS AND RESULTS: 252 patients admitted for ventricular arrhythmia related to CAD were included: 149 had acute myocardial infarction (MI) (Group I, 59%), 54 had significant chronic obstructive CAD suggestive of an ischaemic arrhythmic trigger (Group II, 21%) and 49 patients had an old MI without residual ischaemia (Group III, 19%). 34% of the patients with scar-related arrhythmias had an LVEF > or =40%. Based on pre-event LVEF evaluation, it can be estimated that less than one quarter of the whole study population had a known chronic MI with severely reduced LVEF. In Group III, the proportion of inferior MI was significantly higher than anterior MI (81 vs. 19%; absolute difference, -62; 95% confidence interval, -45 to -79; P < or = 0.0001), though median LVEF was higher in inferior MI (0.37 +/- 10 vs. 0.29 +/- 10; P = 0.0499). CONCLUSION: Patients included in defibrillator trials represent only a minority of the patients at risk of sudden cardiac death. By applying the current risk stratification strategy based on LVEF, more than one third of the patients with old MI would not have qualified for a prophylactic defibrillator. Our study also suggests that inferior scars may be more prone to ventricular arrhythmia compared to anterior scars.

Indicators for the total number of melanocytic naevi : an adjunct for screening campaigns. Observational study on 292 patients.

BACKGROUND: The presence of multiple melanocytic naevi is a strong risk factor for melanoma. Use of the whole body naevus count to identify at-risk patients is impractical. OBJECTIVES: To (i) identify a valid anatomical predictor of total naevus count; (ii) determine the number of naevi that most accurately predict total naevus count above 25, 50 and 100; and (iii) evaluate determinants of multiple melanocytic naevi and atypical naevi. METHODS: Clinical data from 292 consecutive Spanish patients consulting for skin lesions requiring debriding were collected throughout 2009 and 2010. Correlations between site-specific and whole body naevus counts were analysed. Cut-offs to predict total naevus counts were determined using the area under the receiver operating characteristic curve. RESULTS: The studied population was young (median age 31 years, interquartile range 28-43). The naevus count on the right arm correlated best with the total nevus count (R(2) 0·80 for men, 0·86 for women). Presence of at least five naevi on the right arm was the strongest determinant of a total naevus count above 50 [odds ratio (OR) 34·4, 95% confidence interval (CI) 13·9-85·0] and of having at least one atypical naevus (OR 5·7, 95% CI 2·4-13·5). Cut-off values of 6, 8 and 11 naevi on the right arm best predicted total naevus count above 25, 50 and 100, respectively. CONCLUSIONS: Our results support the arm as a practical and reliable site to estimate the total naevus count when screening or phenotyping large populations. Threshold values for the number of naevi on the arm are proposed to help identify patients for melanoma screening.

Endogenous Price Flexibility and Optimal Monetary Policy

Much of the literature on optimal monetary policy uses models in which the degree of nominal price flexibility is exogenous. There are, however, good reasons to suppose that the degree of price flexibility adjusts endogenously to changes in monetary conditions. This paper extends the standard New Keynesian model to incorporate an endogenous degree of price flexibility. The model shows that endogenising the degree of price flexibility tends to shift optimal monetary policy towards complete inflation stabilisation, even when shocks take the form of cost-push disturbances. This contrasts with the standard result obtained in models with exogenous price flexibility, which show that optimal monetary policy should allow some degree of inflation volatility in order to stabilise the welfarerelevant output gap.

Malaria vaccine development using synthetic peptides as a technical platform.

The review covers the development of synthetic peptides as vaccine candidates for Plasmodium falciparum- and Plasmodium vivax-induced malaria from its beginning up to date and the concomitant progress of solid phase peptide synthesis (SPPS) that enables the production of long peptides in a routine fashion. The review also stresses the development of other complementary tools and actions in order to achieve the long sought goal of an efficacious malaria vaccine.

A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology.

BACKGROUND: Pathogen reduction of platelets (PRT-PLTs) using riboflavin and ultraviolet light treatment has undergone Phase 1 and 2 studies examining efficacy and safety. This randomized controlled clinical trial (RCT) assessed the efficacy and safety of PRT-PLTs using the 1-hour corrected count increment (CCI(1hour) ) as the primary outcome. STUDY DESIGN AND METHODS: A noninferiority RCT was performed where patients with chemotherapy-induced thrombocytopenia (six centers) were randomly allocated to receive PRT-PLTs (Mirasol PRT, CaridianBCT Biotechnologies) or reference platelet (PLT) products. The treatment period was 28 days followed by a 28-day follow-up (safety) period. The primary outcome was the CCI(1hour) determined using up to the first eight on-protocol PLT transfusions given during the treatment period. RESULTS: A total of 118 patients were randomly assigned (60 to PRT-PLTs; 58 to reference). Four patients per group did not require PLT transfusions leaving 110 patients in the analysis (56 PRT-PLTs; 54 reference). A total of 541 on-protocol PLT transfusions were given (303 PRT-PLTs; 238 reference). The least square mean CCI was 11,725 (standard error [SE], 1.140) for PRT-PLTs and 16,939 (SE, 1.149) for the reference group (difference, -5214; 95% confidence interval, -7542 to -2887; p<0.0001 for a test of the null hypothesis of no difference between the two groups). CONCLUSION: The study failed to show noninferiority of PRT-PLTs based on predefined CCI criteria. PLT and red blood cell utilization in the two groups was not significantly different suggesting that the slightly lower CCIs (PRT-PLTs) did not increase blood product utilization. Safety data showed similar findings in the two groups. Further studies are required to determine if the lower CCI observed with PRT-PLTs translates into an increased risk of bleeding.

Formes et fonctions de la réécriture des écrits apocryphes chrétiens

Le séminaire de recherche s'est proposé d'examiner quelles pouvaient être les fonctions que des textes qualifiés d'apocryphes, et en l'occurrence d'apocryphes chrétiens, remplissaient dans les processus de communication liés au fonctionnement des institutions dans le christianisme ancien. Il s'est agi en effet d'observer de quelles manières et dans quelles conditions, pour que ces fonctions puissent continuer à être assurées, la matière véhiculée par des apocryphes a été reprise en partie par d'autres genres de textes, voire par d'autres genres de supports. Ce projet nécessitait une diversité d'approches, comme la théorie littéraire, l'analyse des textes, la sociologie de la littérature, ainsi que l'histoire de l'art. C'est selon ces différentes perspectives qu'ont pu être menées l'étude des conditions de production et de circulation des textes et l'observation des changements de forme, des stratégies et des modalités de la communication en rapport avec la transformation des institutions chrétiennes et des instances qui détiennent une autorité.