Auditory spatial deficits following hemispheric lesions : dissociation of explicit and implicit processing

Les déficits auditifs spatiaux se produisent fréquemment après une lésion hémisphérique ; un précédent case report suggérait que la capacité explicite à reconnaître des positions sonores, comme dans la localisation des sons, peut être atteinte alors que l'utilisation implicite d'indices sonores pour la reconnaissance d'objets sonores dans un environnement bruyant reste préservée. En testant systématiquement des patients avec lésion hémisphérique inaugurale, nous avons montré que (1) l'utilisation explicite et/ou implicite des indices sonores peut être perturbée ; (2) la dissociation entre l'atteinte de l'utilisation explicite des indices sonores versus une préservation de l'utilisation implicite de ces indices est assez fréquente ; et (3) différents types de déficits dans la localisation des sons peuvent être associés avec une utilisation implicite préservée de ces indices sonores. Conceptuellement, la dissociation entre l'utilisation explicite et implicite de ces indices sonores peut illustrer la dichotomie des deux voies du système auditif. Nos résultats parlent en faveur d'une évaluation systématique des fonctions auditives spatiales dans un contexte clinique, surtout quand l'adaptation à un environnement sonore est en jeu. De plus, des études systématiques sont nécessaires afin de mettre en lien les troubles de l'utilisation explicite versus implicite de ces indices sonores avec les difficultés à effectuer les activités de la vie quotidienne, afin d'élaborer des stratégies de réhabilitation appropriées et afin de s'assurer jusqu'à quel point l'utilisation explicite et implicite des indices spatiaux peut être rééduquée à la suite d'un dommage cérébral.

Maternal coping, appraisals and adjustment following diagnosis of fetal anomaly.

OBJECTIVE: So far, associations between appraisals, maternal adjustment and coping following diagnosis of fetal anomaly have not been investigated in women who continue with their pregnancy. METHOD: This study measured maternal coping and adjustment after and appraisal of a diagnosis of fetal anomaly in 40 mothers who had continued with their pregnancy using a cross-sectional questionnaire design. RESULTS: Based on retrospective reporting, 35% of participants met full diagnostic criteria for post-traumatic stress disorder after having received the diagnosis. Women were significantly more depressed (p < 0.001) and anxious (p < 0.001) and reported significantly less positive affect (p < 0.05) after having received the diagnosis in comparison to the time after childbirth. There were no significant differences between emotion-focused and problem-focused coping. Stressful life events, women's age, number of people providing support and problem-focused coping explained 57.6% of variance in anxiety and depression after childbirth. Satisfaction with social support, emotion-focused coping and problem-focused coping significantly explained 40.6% of variance in positive affect after childbirth. CONCLUSION: Following a prenatal diagnosis and for the remainder of their pregnancy, particular attention should be paid to older mothers, those experiencing additional stressful life events and those who are socially isolated, as these women may experience greater distress after childbirth.

Combined clonotyping and gene signatures of individual tumor-reactive CD8 T-cells define their functional relevance following peptide vaccination in melanoma patients

Novel cancer vaccines are capableto efficiently induce and boost humantumor antigen specific T-cells. However,the properties of these CD8T-cells are only partially characterized.For in depth investigation ofT-cells following Melan-A/MART-1peptide vaccination in melanoma patients,we conducted a detailed prospectivestudy at the single cell level.We first sorted individual human naiveand effector CD8 T-cells from peripheralblood by flow cytometry, andtested a modified RT-PCR protocolincluding a global amplification ofexpressed mRNAs to obtain sufficientcDNAfromsingle cells.We successfullydetected the expression ofseveral specific genes of interest evendown to 106-fold dilution (equivalentto 10-5 cell). We then analyzed tumor-specific effector memory (EM)CD8T-cell subpopulations ex vivo, assingle cells from vaccinated melanomapatients. To elucidate the hallmarksof effective immunity the genesignatures were defined by a panel ofgenes related to effector functions(e.g. IFN-, granzyme B, perforin),and individual clonotypes were identifiedaccording to the expression ofdistinct T-cell receptors (TCR). Usingthis novel single cell analysis approach,we observed that T-cell differentiationis clonotype dependent,with a progressive restriction in TCRBV clonotype diversity from EMCD28pos to EMCD28neg subsets. However,the effector function gene imprintingis clonotype-independent,but dependent on differentiation,since it correlates with the subset oforigin (EMCD28pos or EMCD28neg). We also conducted a detailedcomparative analysis after vaccinationwith natural vs. analog Melan-Apeptide. We found that the peptideused for vaccination determines thefunctional outcome of individualT-cell clonotypes, with native peptideinducing more potent effector functions.Yet, selective clonotypic expansionwith differentiation was preservedregardless of the peptide usedfor vaccination. In summary, the exvivo single cell RT-PCR approach ishighly sensitive and efficient, andrepresents a reliable and powerfultool to refine our current view of molecularprocesses taking place duringT-cell differentiation.

Superficial and deep changes of cellular mechanical properties following cytoskeleton disassembly.

The cytoskeleton, composed of actin filaments, intermediate filaments, and microtubules, is a highly dynamic supramolecular network actively involved in many essential biological mechanisms such as cellular structure, transport, movements, differentiation, and signaling. As a first step to characterize the biophysical changes associated with cytoskeleton functions, we have developed finite elements models of the organization of the cell that has allowed us to interpret atomic force microscopy (AFM) data at a higher resolution than that in previous work. Thus, by assuming that living cells behave mechanically as multilayered structures, we have been able to identify superficial and deep effects that could be related to actin and microtubule disassembly, respectively. In Cos-7 cells, actin destabilization with Cytochalasin D induced a decrease of the visco-elasticity close to the membrane surface, while destabilizing microtubules with Nocodazole produced a stiffness decrease only in deeper parts of the cell. In both cases, these effects were reversible. Cell softening was measurable with AFM at concentrations of the destabilizing agents that did not induce detectable effects on the cytoskeleton network when viewing the cells with fluorescent confocal microscopy. All experimental results could be simulated by our models. This technology opens the door to the study of the biophysical properties of signaling domains extending from the cell surface to deeper parts of the cell.

Can a targeted psychological intervention be effective for young people following a first manic episode? Results from an 18-month pilot study.

Aim: There is a scarce literature describing psychological interventions for a young, first-episode cohort who have experienced psychotic mania. This study aimed to assess whether a manualized psychological intervention could be effective in reducing symptomatology and relapse, and improve functional outcome in this population. Methods: The study was an open-label design, drawn from a larger pharmacotherapy trial. All participants in the pharmacotherapy trial were offered a manualized psychological intervention in addition to case management. Inclusion in the psychotherapy group was based on participant's choice, and on completion of four or more of the eight modules offered. All clinical files were audited to ensure accuracy of group allocation. Forty young people aged 15 to 25 years old who had experienced a manic episode with psychotic features were recruited into the study, with 20 people in the combined treatment as usual plus psychotherapy group (P+TAU), and an equal number of matched control participants who received treatment as usual (TAU) within the same service. All participants were prescribed antipsychotic and mood-stabilizing medication. Symptomatic, functional and relapse measures were taken both at baseline and at 18-month follow-up. Results: Manic symptoms improved significantly for both groups, with no differences between groups. Depression scores and overall symptom severity were significantly lower in the P + TAU group. No differences were evident between groups with regard to numbers or type of relapse. The P + TAU group had significantly better social and occupational functioning after 18 months. Conclusion: This study suggests that a manualized psychological intervention targeted to a first-episode population can be effective in reducing depression and overall symptom severity, and can improve functional outcome following a first episode of psychotic mania.

Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure.

PURPOSE: To analyze final long-term survival and clinical outcomes from the randomized phase III study of sunitinib in gastrointestinal stromal tumor patients after imatinib failure; to assess correlative angiogenesis biomarkers with patient outcomes. EXPERIMENTAL DESIGN: Blinded sunitinib or placebo was given daily on a 4-week-on/2-week-off treatment schedule. Placebo-assigned patients could cross over to sunitinib at disease progression/study unblinding. Overall survival (OS) was analyzed using conventional statistical methods and the rank-preserving structural failure time (RPSFT) method to explore cross-over impact. Circulating levels of angiogenesis biomarkers were analyzed. RESULTS: In total, 243 patients were randomized to receive sunitinib and 118 to placebo, 103 of whom crossed over to open-label sunitinib. Conventional statistical analysis showed that OS converged in the sunitinib and placebo arms (median 72.7 vs. 64.9 weeks; HR, 0.876; P = 0.306) as expected, given the cross-over design. RPSFT analysis estimated median OS for placebo of 39.0 weeks (HR, 0.505, 95% CI, 0.262-1.134; P = 0.306). No new safety concerns emerged with extended sunitinib treatment. No consistent associations were found between the pharmacodynamics of angiogenesis-related plasma proteins during sunitinib treatment and clinical outcome. CONCLUSIONS: The cross-over design provided evidence of sunitinib clinical benefit based on prolonged time to tumor progression during the double-blind phase of this trial. As expected, following cross-over, there was no statistical difference in OS. RPSFT analysis modeled the absence of cross-over, estimating a substantial sunitinib OS benefit relative to placebo. Long-term sunitinib treatment was tolerated without new adverse events.

Mutism and Amnesia following High-Voltage Electrical Injury: Psychogenic Symptomatology Triggered by Organic Dysfunction?

Background: Mutism and dense retrograde amnesia are found both in organic and dissociative contexts. Moreover, dissociative symptoms may be modulated by right prefrontal activity. A single case, M.R., developed left hemiparesis, mutism and retrograde amnesia after a high-voltage electric shock without evidence of lasting brain lesions. M.R. suddenly recovered from his mutism following a mild brain trauma 2 years later. Methods: M.R.'s neuropsychological pattern and anatomoclinical correlations were studied through (i) language and memory assessment to characterize his deficits, (ii) functional neuroimaging during a standard language paradigm, and (iii) assessment of frontal and left insular connectivity through diffusion tractography imaging and transcranial magnetic stimulation. A control evaluation was repeated after recovery. Findings: M.R. recovered from the left hemiparesis within 90 days of the accident, which indicated a transient right brain impairment. One year later, neurobehavioral, language and memory evaluations strongly suggested a dissociative component in the mutism and retrograde amnesia. Investigations (including MRI, fMRI, diffusion tensor imaging, EEG and r-TMS) were normal. Twenty-seven months after the electrical injury, M.R. had a very mild head injury which was followed by a rapid recovery of speech. However, the retrograde amnesia persisted. Discussion: This case indicates an interaction of both organic and dissociative mechanisms in order to explain the patient's symptoms. The study also illustrates dissociation in the time course of the two different dissociative symptoms in the same patient.

Characterizing emission and breathing-zone concentrations following exposure cases to fluororesin-based waterproofing spray mists.

Measurements and simulations were performed to assess workers' exposure to solvent vapors and aerosols during the waterproofing of a tiled surface. This investigation followed two recent incidents in the same company where workers experienced acute respiratory illness after spraying a stain-repellent resin containing fluorinated polymers on stone-tiled walls and floors. Because the waterproofing activity had been done for years at the tile company without encountering any exposure problems prior to these cases, it was strongly suspected that the incidents were linked to a recent change in the composition of the coating mixture. Experimental measurements and simulations indicated that the emission rate of particles smaller than 10 microm may be estimated at 0.66 mg/sec (SD 0.10) for the old resin and at 0.37 mg/sec (SD 0.04) for the new one. The measurement of the solvent emission rate from surfaces coated with the two resins indicated that shortly after spraying, the emission was in the range of 18 to 20 mg/sec x m2 and was similar for both products. Solvent and overspray emission rates were introduced in a two-zone compartment model. The results obtained in the near-field indicate significant exposure to overspray mist (7 and 34 mg/m3 for new resin) and solvent vapors (80 to 350 ppm for the new resin). It was also shown that the introduction of the new resin tended to significantly decrease the levels of solvents and particulates in the workers' breathing zone. These results strongly suggest that cases of acute respiratory illness are related to the specific toxicity of the fluorinated polymer itself. The fact that the same polymer is used in various commercial products raises concern regarding other possible occupational and domestic exposures.

Resuming motor vehicle driving following orthopaedic surgery or limb trauma.

Following elective orthopaedic surgery or the treatment of a fracture, patients are temporarily unable to drive. This loss of independence may have serious social and economic consequences for the patient. It is therefore essential to know when it is safe to permit such patients to return to driving. This article, based upon a review of the current literature, proposes recommendations of the time period after which patients may safely return to driving. Practical decisions are made based upon the type of surgical intervention or fracture. Swiss legislation is equally approached so as to better define the decision.

Available evidence on re-irradiation with stereotactic ablative radiotherapy following high-dose previous thoracic radiotherapy for lung malignancies.

Patients affected with intra-thoracic recurrences of primary or secondary lung malignancies after a first course of definitive radiotherapy have limited therapeutic options, and they are often treated with a palliative intent. Re-irradiation with stereotactic ablative radiotherapy (SABR) represents an appealing approach, due to the optimized dose distribution that allows for high-dose delivery with better sparing of organs at risk. This strategy has the goal of long-term control and even cure. Aim of this review is to report and discuss published data on re-irradiation with SABR in terms of efficacy and toxicity. Results indicate that thoracic re-irradiation may offer satisfactory disease control, however the data on outcome and toxicity are derived from low quality retrospective studies, and results should be cautiously interpreted. As SABR may be associated with serious toxicity, attention should be paid for an accurate patients' selection.

Trends in fish prey capture by common terns following zebra mussel invasion : do terns track fish species abundance? /

The Common Tern (Sterna hirundo) is a ground nesting colonial seabird. Terns rely primarily on small prey fishes which they obtain through plunge diving for their survival as well as the survival of their offspring during the breeding season. The zebra mussel (Dreissena polymorpha) is a small bivalve mollusk that invaded North American waters in the late 1980's. Through its suspension feeding, the zebra mussel has the ability to alter the entire aquatic ecosystem, ultimately leading to a reduction in pelagic organisms including small prey fish. The objective of the study was to determine what (if any) indirect effects the invasion of the zebra mussel has had on fish prey captured by terns. The study took place in two separate two-year periods, 1990-91 and 1995-96 on a concrete breakwall off the north shore of Lake Erie near Port Colborne, Ontario. Daily nest checks revealed clutch initiation dates, egg-laying chronology, hatching success and morphological egg characteristics (length and breadth). Behavioural observations included time each sex spent in attendance with its brood, the frequency of feeding chicks and the prey species composition and size fed to chicks as well as to females (courtship feeding). Egg sizes did not differ between study periods, nor did feeding rates to chicks, suggesting that food was not a limiting resource. Terns spent less time with their broods (more time foraging) in the 1995-96 period. However, they also had significantly larger broods and fledged more offspring. The time of each individual foraging trip decreased, suggesting that fish were easier to obtain in 1995 and 1996. Lastly, kleptoparasitism rates decreased, suggesting that the costs of foraging (time, energy) actually decreased as fewer birds adopted this strategy to compensate for what I assumed to be a lack of available food (fish). The only significant difference between the periods of 1990, 1991 and 1995, 1996 was a change in diet. Terns delivered significantly fewer rainbow smelt and more emerald shiner in 1995 and 1996. However, the average size of fish delivered did not change. Thus, there was little impact on prey captured by Common Terns in Lake Erie since the invasion of the zebra mussel.

Graffiti, memory and contested space : mnemonic initiatives following trauma and/or repression in Buenos Aires, Argentina

Graffiti, Memory and Contested Space: Mnemonic Initiatives Following Periods of Trauma and/or Repression in Buenos Aires, Argentina This thesis concerns the popular articulation ofmemory following periods or incidents of trauma in Argentina. I am interested in how groups lay claim to various public spaces in the city and how they convert these spaces into mnemonic battlegrounds. In considering these spaces of trauma and places of memory, I am primarily interested in how graffiti writing (stencils, spray-paint, signatures, etchings, wall-paintings, murals and installations) is used to make these spaces transmit particular memories that impugn official versions of the past. This thesis draws on literatures focused on popular/public memory. Scholars argue that memory is socially constructed and thus actively contested. Marginal initiatives such as graffiti writing challenge the memory projects of the state as well as state projects that are perceived by citizens to be 'inadequate,' 'inappropriate,' and/or as promoting the erasure of memory. Many of these initiatives are a reaction to the proreconciliation and pro-oblivion strategies of previous governments. I outline that the history of silences and impunity, and a longstanding emphasis on reconciliation at the expense of truth and justice has created an environment of vulnerable memory in Argentina. Popular memory entrepreneurs react by aggressively articulating their memories in time and in space. As a result of this intense memory work, the built landscape in Buenos Aires is dotted with mnemonic initiatives that aim to contradict or subvert officially sanctioned memories. I also suggest that memory workers in Argentina persistently and carefially use the sites of trauma as well as key public spaces to ensure official as well as popular audiences . The data for this project was collected in five spaces in Buenos Aires, the Plaza de Mayo, Plaza Congreso, La Republica Cromanon nightclub, Avellaneda Train Station and El Olimpo, a former detention centre from the military dictatorship.