Mediterranean populations of the lesser white-toothed shrew (Crocidura suaveolens group): an unexpected puzzle of Pleistocene survivors and prehistoric introductions.

An earlier study revealed the strong phylogeographical structure of the lesser white-toothed shrew (Crocidura suaveolens group) within the northern Palaearctic. Here, we aim to reconstruct the colonization history of Mediterranean islands and to clarify the biogeography and phylogeographical relationships of the poorly documented Middle East region with the northern Palaearctic. We performed analyses on 998-bp-long haplotypes of the mitochondrial cytochrome b gene of 143 samples collected around the Mediterranean basin, including islands and the Middle East. The analyses suggest that the Cypriot shrew belongs to the rare group of relict insular Pleistocene mammal taxa that have survived to the present day. In contrast, the Cretan, Corsican and Menorcan populations were independently introduced from the Middle East during the Holocene. The phylogeographical structure of this temperate Palaearctic species within the Middle East appears to be complex and rich in diversity, probably reflecting fragmentation of the area by numerous mountain chains. Four deeply divergent clades of the C. suaveolens group occur in the area, meaning that a hypothetical contact zone remains to be located in central western Iran.

Five-day plan for smoking cessation using group behaviour therapy.

The "Five-Day Plan to Stop Smoking" (FDP) is an educational group technique for smoking cessation. We studied a cohort of 123 smokers (55 men, 68 women, mean age 42 years) who participated in 11 successive FDP sessions held in Switzerland between 1995 and 1998 and who were followed up for at least 12 months by telephone or direct interview. Overall, 102 of the 123 subjects (83%) had stopped smoking by the end of the FDP, and self-declared smoking cessation rate was 25% after one year. The following factors potentially associated with outcome were studied: age, sex, smoking habit duration, cigarettes per day, Fagerström Test for Nicotine Dependence (FTND), group size, and medical presence among the group leaders. Smoking habit duration was the only variable which showed a statistically significant association with success: the rate of smoking cessation was higher among patients who had smoked for less than 20 years (34.7% vs. 18.9%, p = 0.049). Stress was the most common cause of relapse. The FDP appears to be an effective smoking cessation therapy. Propositions are made in order to improve the success rate of future sessions.

Acute flare induced by the calcific tendonitis of the rotator cuff: inhibition of IL-1 a potential therapeutic target?

Introduction: Calcific tendonitis of rotator cuff is observed on plainradiographs in 10% of adults, but remains asymptomatic in half thesecases. Sometimes, these calcifications induce acute flares withmassive inflammation similar to gout or CPPD crisis. Analgesics/anti-inflammatory medications are usually not sufficient to controlssymptoms in these situations. Local steroid infiltration with or withoutremoval of the calcific deposition with a needle aspiration may beuseful. A new approach could be IL-1 inhibitors. Indeed, basic calciumphosphate crystals are capable of stimulating the release of activeIL-1β in vitro. These crystals trigger IL-1β release, in an analogousmanner to MSU crystals in acute gout, suggesting that IL-1β blockademay be clinically useful.Case presentation: This report describes a 70-year old woman withacute rest pain of the right shoulder since 48 hours. On examination,we found massive limitations of active and passive movements. Thepatient evaluated, on the visual scale, her symptoms at 10/10 the nightand 5/10 the day. The radiography and showed a rounded, 8 mmcalcification in the subscapularis tendon. The ultrasound aspectrevealed a heterogeneous calcification partially non solid, surroundedby massive inflammation on Doppler. C-reactive protein anderythrocyte sedimentation rate were high (74 mg/ml, 54 mm/hour).The patient received subcutaneous injections of anakinra: 100 mgdaily for 3 days (D1-D3). We evaluated the patient in our consult at dayD1, D2, D3, D7, D16 and by phone at D70.This treatment rapidly relieved the inflammatory symptoms (within afew hours with no relapse). The mobility of the shoulder, the biologicsparameters improved and the size of the calcification as well thedegree of inflammation regressed on ultrasound after 3 days.Conclusion: This is the first report of a woman with an acute flareinduced by calcific tendonitis who received anakinra. IL-1 inhibitionmay be a therapeutic target in calcific tendonitis. To analyse thisresponse more precisely and elaborate definitive conclusions, aprospective pilot study is on-going in our ambulatory institute.

The Measurement of social polarization in a multi-group context

Polarization indices presented up to now have only focused their attention on the distribution of income/wealth. However, in many circumstances income is not the only relevant dimension that might be the cause of social conflict, so it is very important to have a social polarization index able to cope with alternative dimensions. In this paper we present an axiomatic characterization of one of such indices: it has been obtained as an extension of the (income) polarization measure introduced in Duclos, Esteban and Ray (2004) to a wider domain. It turns out that the axiomatic structure introduced in that paper alone is not appropriate to obtain a fully satisfactory characterization of our measure, so additional axioms are proposed. As a byproduct, we present an alternative axiomatization of the aforementioned income polarization measure.

A new Culicoides of the stigmalis group (Diptera: Ceratopogonidae)

Notes are presented on the three known Neotropical species of the Culicoides stigmalis group of boodsucking midges: alvarezi Ortiz, fluviatilis (Lutz), stigmalis Wirth, and on deanei n.sp., which is described from the state of Rio de Janeiro, Brazil. A diagnosis is given for the group, as well as a key for identification and comparative phtographs of the female wings.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 2: T2 substaging and prostate cancer volume.

The 2009 International Society of Urological Pathology consensus conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the substaging of pT2 prostate cancers according to the TNM 2002/2010 system, reporting of tumor size/volume and zonal location of prostate cancers were coordinated by working group 2. A survey circulated before the consensus conference demonstrated that 74% of the 157 participants considered pT2 substaging of prostate cancer to be of clinical and/or academic relevance. The survey also revealed a considerable variation in the frequency of reporting of pT2b substage prostate cancer, which was likely a consequence of the variable methodologies used to distinguish pT2a from pT2b tumors. Overview of the literature indicates that current pT2 substaging criteria lack clinical relevance and the majority (65.5%) of conference attendees wished to discontinue pT2 substaging. Therefore, the consensus was that reporting of pT2 substages should, at present, be optional. Several studies have shown that prostate cancer volume is significantly correlated with other clinicopathological features, including Gleason score and extraprostatic extension of tumor; however, most studies fail to demonstrate this to have prognostic significance on multivariate analysis. Consensus was reached with regard to the reporting of some quantitative measure of the volume of tumor in a prostatectomy specimen, without prescribing a specific methodology. Incorporation of the zonal and/or anterior location of the dominant/index tumor in the pathology report was accepted by most participants, but a formal definition of the identifying features of the dominant/index tumor remained undecided.

Primary localized rectal/pararectal gastrointestinal stromal tumors: results of surgical and multimodal therapy from the French Sarcoma group.

BACKGROUND: Rectal and pararectal gastrointestinal stromal tumors (GISTs) are rare. The optimal management strategy for primary localized GISTs remains poorly defined. METHODS: We conducted a retrospective analysis of 41 patients with localized rectal or pararectal GISTs treated between 1991 and 2011 in 13 French Sarcoma Group centers. RESULTS: Of 12 patients who received preoperative imatinib therapy for a median duration of 7 (2-12) months, 8 experienced a partial response, 3 had stable disease, and 1 had a complete response. Thirty and 11 patients underwent function-sparing conservative surgery and abdominoperineal resection, respectively. Tumor resections were mostly R0 and R1 in 35 patients. Tumor rupture occurred in 12 patients. Eleven patients received postoperative imatinib with a median follow-up of 59 (2.4-186) months. The median time to disease relapse was 36 (9.8-62) months. The 5-year overall survival rate was 86.5%. Twenty patients developed local recurrence after surgery alone, two developed recurrence after resection combined with preoperative and/or postoperative imatinib, and eight developed metastases. In univariate analysis, the mitotic index (≤5) and tumor size (≤5 cm) were associated with a significantly decreased risk of local relapse. Perioperative imatinib was associated with a significantly reduced risk of overall relapse and local relapse. CONCLUSIONS: Perioperative imatinib therapy was associated with improved disease-free survival. Preoperative imatinib was effective. Tumor shrinkage has a clear benefit for local excision in terms of feasibility and function preservation. Given the complexity of rectal GISTs, referral of patients with this rare disease to expert centers to undergo a multidisciplinary approach is recommended.

Food habits and sport activity during adolescence: differences between athletic and non-athletic teenagers in Switzerland.

OBJECTIVE: To describe food habits and dietary intakes of athletic and non-athletic adolescents in Switzerland. SETTING: College, high schools and professional centers in the Swiss canton of Vaud. METHOD: A total of 3,540 subjects aged 9-19 y answered a self-reported anonymous questionnaire to assess lifestyles, physical plus sports activity and food habits. Within this sample, a subgroup of 246 subjects aged 11-15 also participated in an in-depth ancillary study including a 3 day dietary record completed by an interview with a dietician. RESULTS: More boys than girls reported engaging in regular sports activities (P<0.001). Adolescent food habits are quite traditional: up to 15 y, most of the respondents have a breakfast and eat at least two hot meals a day, the percentages decreasing thereafter. Snacking is widespread among adolescents (60-80% in the morning, 80-90% in the afternoon). Food habits among athletic adolescents are healthier and also are perceived as such in a higher proportion. Among athletic adolescents, consumption frequency is higher for dairy products and ready to eat (RTE) cereals, for fruit, fruit juices and salad (P<0.05 at least). Thus the athletic adolescent's food brings more micronutrients than the diet of their non-athletic counterparts. Within the subgroup (ancillary study), mean energy intake corresponds to requirements for age/gender group. CONCLUSIONS: Athletic adolescents display healthier food habits than non-athletic adolescents: this result supports the idea that healthy behavior tends to cluster and suggests that prevention programs among this age group should target simultaneously both sports activity and food habits.

Epidermal growth factor receptor: a re-emerging target in glioblastoma.

PURPOSE OF REVIEW: Amplification and overexpression of the epidermal growth factor receptor (EGFR) gene are a hallmark of primary glioblastoma (45%), making it a prime target for therapy. In addition, these amplifications are frequently associated with oncogenic mutations in the extracellular domain. However, efforts at targeting the EGFR tyrosine kinase using small molecule inhibitors or antibodies have shown disappointing efficacy in clinical trials for newly diagnosed or recurrent glioblastoma. Here, we review recent insights into molecular mechanisms relevant for effective targeting of the EGFR pathway. RECENT FINDINGS: Molecular workup of glioblastoma tissue of patients under treatment with small molecule inhibitors has established drug concentrations in the tumor tissue, and has shed light on the effectiveness of target inhibition and respective effects on pathway signaling. Further, functional analyses of interaction of small molecule inhibitors with distinct properties to bind to the active or inactive form of EGFR have provided new insights that will impact the choice of drugs. Finally, vaccination approaches targeting the EGFRvIII mutant featuring a tumor-specific antigen have shown promising results that warrant larger controlled clinical trials. SUMMARY: A combination of preclinical and clinical studies at the molecular level has provided new insights that will allow refining strategies for targeting the EGFR pathway in glioblastoma.

Quantifying consistency of Event Related Potentials across subjects based on single-trial topographic analysis

Introduction: Non-invasive brain imaging techniques often contrast experimental conditions across a cohort of participants, obfuscating distinctions in individual performance and brain mechanisms that are better characterised by the inter-trial variability. To overcome such limitations, we developed topographic analysis methods for single-trial EEG data [1]. So far this was typically based on time-frequency analysis of single-electrode data or single independent components. The method's efficacy is demonstrated for event-related responses to environmental sounds, hitherto studied at an average event-related potential (ERP) level. Methods: Nine healthy subjects participated to the experiment. Auditory meaningful sounds of common objects were used for a target detection task [2]. On each block, subjects were asked to discriminate target sounds, which were living or man-made auditory objects. Continuous 64-channel EEG was acquired during the task. Two datasets were considered for each subject including single-trial of the two conditions, living and man-made. The analysis comprised two steps. In the first part, a mixture of Gaussians analysis [3] provided representative topographies for each subject. In the second step, conditional probabilities for each Gaussian provided statistical inference on the structure of these topographies across trials, time, and experimental conditions. Similar analysis was conducted at group-level. Results: Results show that the occurrence of each map is structured in time and consistent across trials both at the single-subject and at group level. Conducting separate analyses of ERPs at single-subject and group levels, we could quantify the consistency of identified topographies and their time course of activation within and across participants as well as experimental conditions. A general agreement was found with previous analysis at average ERP level. Conclusions: This novel approach to single-trial analysis promises to have impact on several domains. In clinical research, it gives the possibility to statistically evaluate single-subject data, an essential tool for analysing patients with specific deficits and impairments and their deviation from normative standards. In cognitive neuroscience, it provides a novel tool for understanding behaviour and brain activity interdependencies at both single-subject and at group levels. In basic neurophysiology, it provides a new representation of ERPs and promises to cast light on the mechanisms of its generation and inter-individual variability.

Results of a collaborative study of the EDNAP group regarding mitochondrial DNA heteroplasmy and segregation in hair shafts.

A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in order to evaluate the distribution of mitochondrial DNA (mtDNA) heteroplasmy amongst the hairs of an individual who displays point heteroplasmy in blood and buccal cells. A second aim of the exercise was to study reproducibility of mtDNA sequencing of hairs between laboratories using differing chemistries, further to the first mtDNA reproducibility study carried out by the EDNAP group. Laboratories were asked to type 2 sections from each of 10 hairs, such that each hair was typed by at least two laboratories. Ten laboratories participated in the study, and a total of 55 hairs were typed. The results showed that the C/T point heteroplasmy observed in blood and buccal cells at position 16234 segregated differentially between hairs, such that some hairs showed only C, others only T and the remainder, C/T heteroplasmy at varying ratios. Additionally, differential segregation of heteroplasmic variants was confirmed in independent extracts at positions 16093 and the poly(C) tract at 302-309, whilst a complete A-G transition was confirmed at position 16129 in one hair. Heteroplasmy was observed at position 16195 on both strands of a single extract from one hair segment, but was not observed in the extracts from any other segment of the same hair. Similarly, heteroplasmy at position 16304 was observed on both strands of a single extract from one hair. Additional variants at positions 73, 249 and the HVII poly(C) region were reported by one laboratory; as these were not confirmed in independent extracts, the possibility of contamination cannot be excluded. Additionally, the electrophoresis and detection equipment used by this laboratory was different to those of the other laboratories, and the discrepancies at position 249 and the HVII poly(C) region appear to be due to reading errors that may be associated with this technology. The results, and their implications for forensic mtDNA typing, are discussed in the light of the biology of hair formation.

The potassium impermeable apical membrane of insect epithelia: a target for development of safe pesticides

Columnar cell apical membranes (CCAM) in series with goblet cell apical membranes (GCAM) form an electroosmotic barrier separating the midgut lumen from epithelial cell cytoplasm. A unique K+ ATPase in GCAM generates three gradients across this barrier. A greater than 180 mV electrical gradient (lumen positive) drives amino acid uptake through voltage-dependent K+ symports. A greater than 1000-fold [H+] gradient (lumen alkaline) and a greater than 10-fold [K+] gradient (lumen concentrated) are adaptations to the high tannin and high K+ content, respectively, in dietary plant material. Agents which act on the apical membrane and disrupt the PD, H+, or K+ gradients are potential insecticides. Insect sensory epithelia and mammalian stria vascularis maintain similar PD and K+ gradients but would not be exposed to ingested anti-apical membrane insecticides. Following the demonstration by Sacchi et al. that Bacillus thuringiensis delta-endotoxin (Bt) induces specifically a K+ conductance increase in CCAM vesicles, we find that the K+ channel blocking agent, Ba2+, completely reverses Bt inhibition of the K+-carried short circuit current in the isolated midgut of Manduca sexta. Progress in characterizing the apical membrane includes finding that fluorosulfonylbenzoyladenosine binds specifically to certain GCAM polypeptides and that CCAM vesicles can be mass produced by Ca2+ or Mg2+ precipitation from Manduca sexta midgut.

Tree automorphisms and quasi-isometries of Thompson's group F

We prove that automorphisms of the infinite binary rooted tree T2 do not yield quasi-isometries of Thompson's group F, except for the map which reverses orientation on the unit interval, a natural outer automorphism of F. This map, together with the identity map, forms a subgroup of Aut(T2) consisting of 2-adic automorphisms, following standard terminology used in the study of branch groups. However, for more general p, we show that the analgous groups of p-adic tree automorphisms do not give rise to quasiisometries of F(p).