Evolution of specialization: a phylogenetic study of host range in the red milkweed beetle (Tetraopes tetraophthalmus).

Specialization is common in most lineages of insect herbivores, one of the most diverse groups of organisms on earth. To address how and why specialization is maintained over evolutionary time, we hypothesized that plant defense and other ecological attributes of potential host plants would predict the performance of a specialist root-feeding herbivore (the red milkweed beetle, Tetraopes tetraophthalmus). Using a comparative phylogenetic and functional trait approach, we assessed the determinants of insect host range across 18 species of Asclepias. Larval survivorship decreased with increasing phylogenetic distance from the true host, Asclepias syriaca, suggesting that adaptation to plant traits drives specialization. Among several root traits measured, only cardenolides (toxic defense chemicals) correlated with larval survival, and cardenolides also explained the phylogenetic distance effect in phylogenetically controlled multiple regression analyses. Additionally, milkweed species having a known association with other Tetraopes beetles were better hosts than species lacking Tetraopes herbivores, and milkweeds with specific leaf area values (a trait related to leaf function and habitat affiliation) similar to those of A. syriaca were better hosts than species having divergent values. We thus conclude that phylogenetic distance is an integrated measure of phenotypic and ecological attributes of Asclepias species, especially defensive cardenolides, which can be used to explain specialization and constraints on host shifts over evolutionary time.

Egg parasitoid wasps as natural enemies of the neotropical stink bug Dichelops melacanthus

The objective of this work was to determine the potential of five species of Scelionidae wasps - Telenomus podisi, Trissolcus basalis, Trissolcus urichi, Trissolcus teretis and Trissolcus brochymenae - as natural enemies of the neotropical stink bug Dichelops melacanthus, and to determine if the presence of eggs of other stink bug species influences the parasitism and development of the parasitoids. Two kinds of experiments were done in laboratory: without choice of hosts (eggs of D. melacanthus) and with choice (eggs of D. melacanthus and of Euschistus heros). Biological parameters, including proportion of parasitism, immature survivorship, progeny sex ratio, immature stage development period, and host preference were recorded. All the evaluated parasitoids can parasitize and develop on D. melacanthus eggs. The first choice of eggs did not influence the proportion of D. melacanthus eggs parasitized by Tr. basalis, Tr. teretis or Tr. brochymenae. However, D. melacanthus eggs as the first choice of Te. podisi and Tr. urichi increased, respectively, 9 and 14 times the chance for parasitism on eggs of this species. Behavioral and ecological aspects of parasitoids should be considered prior to their use in biological control programs.

Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy.

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150 mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17 mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

Latin 12229

Contient : Extraits de S. Augustin, S. Ambroise, S. Jérôme, Cassien et S. Basile ; Traité de S. Anselme sur la béatitude éternelle, précédé d'une lettre d'Eadmer ; Lettres sur l'abstinence adressées aux moines de Préaux

Involuntary treatment of alcohol-dependent patients: a study of 17 consecutive cases of civil commitment.

AIM: To investigate the baseline and follow-up characteristics of a group of alcohol-dependent patients being treated under civil commitment. METHODS: This study involved a cross-sectional comparative analysis of baseline characteristics and a follow-up survey of a group of committed alcoholic patients. The study was undertaken in the Alcohol Unit of a 1,000-bed general and university hospital. The study included 17 consecutive cases of civil commitment (representing 15 patients, of whom 2 were committed twice) and a comparative group of 34 randomly selected age- and sex-matched patients. Baseline characteristics of the cases (at the time of commitment) and of patients from the comparative group were collected from medical records, including sociodemographic data, medical condition, patterns of drinking and number and dates of previous treatments for alcohol-related problems. A structured follow-up interview of the cases provided information on their medical condition, social status, patterns of alcohol use, type and duration of residential treatment as well as their perceptions of commitment. RESULTS: During a 4-year period, our Unit referred 23 cases of alcohol-dependent patients (out of 367) to the Guardianship Authority, requesting civil commitment. On 17 occasions, patients were committed to residential treatment, including 2 patients who underwent commitment on two separate occasions, thus representing a total of 15 different patients. In comparison with age- and sex-matched patients seen at the Unit, the cases were characterized by multiple medical, social and psychological alcohol-related impairments. At the time of follow-up, 14 out of 15 patients were alive, among whom 10 agreed to be interviewed. Eight of these reported complete abstinence, whereas 9 considered their alcohol problem as less severe than before. The average duration of commitment was 29 weeks. The majority of patients retrospectively considered the measure as having been justified and useful. The patients' satisfaction with the decision to commit was higher among women than among men. Health-related quality of life at the time of follow-up, as assessed by the MOS 36-Item Short Form Health Survey questionnaire, was good on average and better than that usually reported by other cohorts of alcoholics undergoing treatment. CONCLUSIONS: The usefulness of residential civil commitment of certain severely impaired alcohol-dependent patients is underscored. This study suggests that civil commitment not only may save the lives of endangered patients but could also be a health-promoting measure that may sometimes allow for recovery from dependence. Unexpectedly, this measure was retrospectively well accepted by many patients, who considered the commitment decision as having been justified and useful.

Ultra-rapid opiate detoxification using deep sedation and prior oral buprenorphine preparation: long-term results.

BACKGROUND: New methods of ultra-rapid opiate detoxification (URD) under intravenous sedation have been criticized because of limited data on safety and long-term follow-up. Premedication with buprenorphine has been advocated to improve safety by decreasing vomiting. Prior research has not explored URD in socially impaired patients. METHOD: Sixteen patients were detoxified with URD and prospectively evaluated over at least 30 months. Data of this procedure were compared with those of our previous study without buprenorphine preparation (Drug Alcohol Depend. 52(3) (1998) 243). The 16 patients were followed up by a general practitioner (GP) before and after URD. The GPs also supervised the 7-day course of buprenorphine treatment prescribed for the 16 patients prior to URD. RESULTS: During the procedure, only one episode of vomiting occurred instead of 13 out of 20 in our previous study. Post-procedure, only two patients experienced moderate withdrawal symptoms, such as persistent nausea, abdominal cramps and vomiting lasting from 24 to 48 h, in comparison with most patients in the previous study without buprenorphine. After a period of at least 30 months (36.0+/-6.38), the 16 patients were still alive and were regularly monitored by their GP. Only two of the 16 never relapsed after URD and reported total opiate abstinence. Fourteen patients relapsed; 12 of these were prescribed a licensed methadone substitution program and two were still using heroin. CONCLUSION: In this small sample, the data indicated that URD with buprenorphine preparation was safe and that it markedly decreased post-procedure morbidity. No patient died over a minimum 30-month follow-up period. Furthermore, the procedure was employed with socially impaired patients. In the long term, a few patients were still free of opiates, while the majority opted for a methadone maintenance program, showing that URD can serve as one possible step in a long-term treatment program.

Normative Topographic ERP Analyses of Speed of Speech Processing and Grammar Before and After Grammatical Treatment.

Typically developing (TD) preschoolers and age-matched preschoolers with specific language impairment (SLI) received event-related potentials (ERPs) to four monosyllabic speech sounds prior to treatment and, in the SLI group, after 6 months of grammatical treatment. Before treatment, the TD group processed speech sounds faster than the SLI group. The SLI group increased the speed of their speech processing after treatment. Posttreatment speed of speech processing predicted later impairment in comprehending phrase elaboration in the SLI group. During the treatment phase, change in speed of speech processing predicted growth rate of grammar in the SLI group.

The Persistence of Finnish Equity Fund Performance

Tutkimuksen tavoitteena on selvittää, esiintyykö suomeen sijoittavilla osakerahastoilla menestyksen pysyvyyttä. Tutkimusaineisto koostuu kaikista suomalaisista osakerahastoista, jotka toimivat ajanjaksolla 15.1.1998-13.1.2005. Aineisto on vapaa selviytymisvinoumasta. Suorituskyvyn mittareina käytetään CAPM-alfaa sekä kolmi- ja nelifaktori-alfaa. Empiirisessä osassa osakerahastojen menestyksen pysyvyyttä testataan Spearmanin järjestyskorrelaatiotestillä. Evidenssi menestyksen pysyvyydestä jäi vähäiseksi, vaikkakin sitä esiintyi satunnaisesti kaikilla menestysmittareilla joillakin ranking- ja sijoitusperiodin yhdistelmillä. CAPM-alfalla tarkasteltuna tilastollisesti merkitsevää menestyksen pysyvyyttä esiintyi selvästi useammin kuin muilla menestysmittareilla. Tulokset tukevat viimeaikaisia kansainvälisiä tutkimuksia, joiden mukaan menestyksen pysyvyys riippuu usein mittaustavasta. Menestysmittareina käytettyjen regressiomallien merkitsevyystestit osoittavat multifaktorimallien selittävän osakerahastojen tuottoja CAPM:a paremmin. Lisätyt muuttujat parantavat merkittävästi CAPM:n selitysvoimaa.

Modern Gamma Knife radiosurgery of vestibular schwannomas: treatment concept, volumetric tumor response, and functional results.

The objective of the present study was longitudinal evaluation of the volumetric tumor response and functional results after Gamma Knife radiosurgery of vestibular schwannomas, performed according to the modern standards of treatment. From October 2003 to September 2007, 133 consecutive patients with vestibular schwannomas were treated according to the concept of robotic Gamma Knife microradiosurgery, which is based on precise irradiation of the lesion, sparing adjacent structures, and delivery of the high radiation energy to the target. Multiple small-sized isocenters located within the border of the neoplasm were applied. The mean marginal dose was 11.5 Gy (range, 11-12 Gy). In total, 126 cases with a minimum posttreatment follow-up of 2 years (range, 2-7 years; median, 4 years) were analyzed. Temporary enlargement was noted in 25 % of tumors at 6 months after radiosurgery. At 3 years of follow-up, tumor shrinkage, stabilization, and increase in volume were marked in 73 %, 23 %, and 4 % of cases, respectively. All progressing lesions spontaneously stabilized later on and did not require additional management. In 3 % of patients, transitory impairment of the facial nerve function was marked; however, neither its permanent dysfunction nor trigeminal neuropathy attributed to radiosurgery was noted. Impairment of hearing compared to its pretreatment level was revealed in 4 %, 12 %, 13 %, and 16 % of patients at 6 months, 1 year, 2 years, and 3 years after radiosurgery, respectively, and this trend was statistically significant (P = 0.0042). Overall, 77 % of patients with serviceable hearing before treatment preserved it 3 years thereafter. In conclusion, modern Gamma Knife radiosurgery provides effective and safe management of vestibular schwannomas. Nevertheless, possible temporary tumor enlargement, delay of its growth arrest, transient dysfunction of the cranial nerves, and gradual deterioration of hearing after irradiation should be always taken into consideration.

Uses of cancer registries for public health and clinical research in Europe : results of the European Network of Cancer Registries survey among 161 population-based cancer registries during 2010-2012

AIM: To provide insight into cancer registration coverage, data access and use in Europe. This contributes to data and infrastructure harmonisation and will foster a more prominent role of cancer registries (CRs) within public health, clinical policy and cancer research, whether within or outside the European Research Area. METHODS: During 2010-12 an extensive survey of cancer registration practices and data use was conducted among 161 population-based CRs across Europe. Responding registries (66%) operated in 33 countries, including 23 with national coverage. RESULTS: Population-based oncological surveillance started during the 1940-50s in the northwest of Europe and from the 1970s to 1990s in other regions. The European Union (EU) protection regulations affected data access, especially in Germany and France, but less in the Netherlands or Belgium. Regular reports were produced by CRs on incidence rates (95%), survival (60%) and stage for selected tumours (80%). Evaluation of cancer control and quality of care remained modest except in a few dedicated CRs. Variables evaluated were support of clinical audits, monitoring adherence to clinical guidelines, improvement of cancer care and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools was only occasional. CONCLUSION: Most population-based CRs are well equipped for strengthening cancer surveillance across Europe. Data quality and intensity of use depend on the role the cancer registry plays in the politico, oncomedical and public health setting within the country. Standard registration methodology could therefore not be translated to equivalent advances in cancer prevention and mass screening, quality of care, translational research of prognosis and survivorship across Europe. Further European collaboration remains essential to ensure access to data and comparability of the results.

Influence of Gilbert's syndrome on the formation of ethyl glucuronide.

A drinking experiment with participants suffering from Gilbert's syndrome was performed to study the possible influence of this glucuronidation disorder on the formation of ethyl glucuronide (EtG). Gilbert's syndrome is a rather common and, in most cases, asymptomatic congenital metabolic aberration with a prevalence of about 5 %. It is characterized by a reduction of the enzyme activity of the uridine diphosphate glucuronosyltransferase (UGT) isoform 1A1 up to 80 %. One of the glucuronidation products is EtG, which is formed in the organism following exposure to ethanol. EtG is used as a short-term marker for ethyl alcohol consumption to prove abstinence in various settings. After 2 days of abstinence from ethanol and giving a void urine sample, 30 study participants drank 0.1 L of sparkling wine (9 g ethanol). 3, 6, 12, and 24 h after drinking, urine samples were collected. 3 hours after drinking, an additional blood sample was taken, in which liver enzyme activities, ethanol, hematological parameters, and bilirubin were measured. EtG and ethyl sulfate (EtS), another short-term marker of ethanol consumption, were determined in the urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS); creatinine was measured photometrically. In all participants, EtG and EtS were detected in concentrations showing a wide range (EtG: 3 h sample 0.5-18.43 mg/L and 6 h sample 0.67-13.8 mg/L; EtS: 3 h sample 0.87-6.87 mg/L and 6 h sample 0.29-4.48 mg/L). No evidence of impaired EtG formation was found. Thus, EtG seems to be a suitable marker for ethanol consumption even in individuals with Gilbert's syndrome.

Severity and burden of partial-onset seizures in a phase III trial of eslicarbazepine acetate.

OBJECTIVE: The objective of this study was to compare posttreatment seizure severity in a phase III clinical trial of eslicarbazepine acetate (ESL) as adjunctive treatment of refractory partial-onset seizures. METHODS: The Seizure Severity Questionnaire (SSQ) was administered at baseline and posttreatment. The SSQ total score (TS) and component scores (frequency and helpfulness of warning signs before seizures [BS]; severity and bothersomeness of ictal movement and altered consciousness during seizures [DS]; cognitive, emotional, and physical aspects of postictal recovery after seizures [AS]; and overall severity and bothersomeness [SB]) were calculated for the per-protocol population. Analysis of covariance, adjusted for baseline scores, estimated differences in posttreatment least square means between treatment arms. RESULTS: Out of 547 per-protocol patients, 441 had valid SSQ TS both at baseline and posttreatment. Mean posttreatment TS for ESL 1200mg/day was significantly lower than that for placebo (2.68 vs 3.20, p<0.001), exceeding the minimal clinically important difference (MCID: 0.48). Mean DS, AS, and SB were also significantly lower with ESL 1200mg/day; differences in AS and SB exceeded the MCIDs. The TS, DS, AS, and SB were lower for ESL 800mg/day than for placebo; only SB was significant (p=0.013). For both ESL arms combined versus placebo, mean scores differed significantly for TS (p=0.006), DS (p=0.031), and SB (p=0.001). CONCLUSIONS: Therapeutic ESL doses led to clinically meaningful, dose-dependent reductions in seizure severity, as measured by SSQ scores. CLASSIFICATION OF EVIDENCE: This study presents Class I evidence that adjunctive ESL (800 and 1200mg/day) led to clinically meaningful, dose-dependent seizure severity reductions, measured by the SSQ.

Intoxication aiguë au baclofène. Particularités et principes thérapeutiques

En raison de sa prescription croissante pour des indications d'aide à la réduction des consommations ou au maintien de l'abstinence à l'alcool, le risque d'intoxication volontaire ou accidentelle au baclofène s'accroît et favorise l'admission aux urgences ou en réanimation de comas profonds. La difficulté diagnostique repose sur une relative méconnaissance de cette substance et sur le fait que le baclofène ne fait pas partie des substances mises en évidence par les examens toxicologiques de dépistage habituels. La modification de la pharmaco- cinétique du baclofène en cas de surdosage expose le patient à un coma prolongé, nécessitant dès lors un soutien ventilatoire de longue durée. De manière paradoxale, le baclofène expose également à un risque potentiel de convulsions. En cas de prise en charge adéquate, le pronostic est excellent dans la majorité des cas. En partant d'un cas clinique illustratif et d'une revue de littérature, nous proposons une synthèse des principes de prise en charge d'une intoxication aiguë au baclofène. Baclofen is widely used for the treatment of neurological spastic syndromes and has been recently proposed for the treatment of alcohol dependence. The risk of accidental or self- intoxication with baclofen may therefore increase in the future. Baclofen overdose affects the autonomic nervous system and produces an inhibitory effect on the central nervous system. The classic clinical presentation involves prolonged impaired consciousness or coma and neurovegetative symptoms. Paradoxically, baclofen overdose may also promote the occurrence of seizures. The emergency management is mainly supportive and, in the majority of cases, the prognosis appears excellent. Herein we report a case of baclofen self-intoxication and review the literature regarding the toxicity of baclofen, the clinical presentation of an acute baclofen poisoning and the related principles of management.

Modelling the consequences of a reduction in alcohol consumption among patients with alcohol dependence based on real-life observational data.

BACKGROUND: Most available pharmacotherapies for alcohol-dependent patients target abstinence; however, reduced alcohol consumption may be a more realistic goal. Using randomized clinical trial (RCT) data, a previous microsimulation model evaluated the clinical relevance of reduced consumption in terms of avoided alcohol-attributable events. Using real-life observational data, the current analysis aimed to adapt the model and confirm previous findings about the clinical relevance of reduced alcohol consumption. METHODS: Based on the prospective observational CONTROL study, evaluating daily alcohol consumption among alcohol-dependent patients, the model predicted the probability of drinking any alcohol during a given day. Predicted daily alcohol consumption was simulated in a hypothetical sample of 200,000 patients observed over a year. Individual total alcohol consumption (TAC) and number of heavy drinking days (HDD) were derived. Using published risk equations, probabilities of alcohol-attributable adverse health events (e.g., hospitalizations or death) corresponding to simulated consumptions were computed, and aggregated for categories of patients defined by HDDs and TAC (expressed per 100,000 patient-years). Sensitivity analyses tested model robustness. RESULTS: Shifting from >220 HDDs per year to 120-140 HDDs and shifting from 36,000-39,000 g TAC per year (120-130 g/day) to 15,000-18,000 g TAC per year (50-60 g/day) impacted substantially on the incidence of events (14,588 and 6148 events avoided per 100,000 patient-years, respectively). Results were robust to sensitivity analyses. CONCLUSIONS: This study corroborates the previous microsimulation modeling approach and, using real-life data, confirms RCT-based findings that reduced alcohol consumption is a relevant objective for consideration in alcohol dependence management to improve public health.

Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Alcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects. METHODS: MEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses. FINDINGS: We identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05). INTERPRETATION: AD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption.