Comparative analysis of MIS capacitance structures with high-k dielectrics under gamma, 16O and p Radiation

MIS capacitance structures, with Hafnium Oxide, Alumina and nanolaminate as dielectrics were studied under gamma photons Co, 25 MeV oxygen ions and 10 MeV protons radiation using capacitance-voltage (C-V) characterization. The main trend of the results shows that the nanolaminates stack presents the highest levels of hysteresis and stretch-out of the C-V curves, suggesting that interface layers between dielectrics could play a relevant role in the study of the radiation response.Fil: Quinteros, C. P.. Comisión Nacional de Energía Atómica; ArgentinaFil: Sambuco Salomone, Lucas Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Redin, Eduardo Gabriel. Universidad de Buenos Aires; ArgentinaFil: Rafí, J. M.. Consejo Superior de Investigaciones Científicas; EspañaFil: Zabala, M.. Consejo Superior de Investigaciones Científicas; EspañaFil: Faigón, A.. Universidad de Buenos Aires; ArgentinaFil: Palumbo, Félix Roberto Mario. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Campabadal, F.. Consejo Superior de Investigaciones Científicas; Españ

Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34+ cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT. Twenty-two individuals (median follow-up 15.4 years) were treated in the context of clinical development or named patient program. Nineteen patients were treated post-marketing authorization (median follow-up 3.2 years), and two additional patients received mobilized peripheral blood CD34+ cell GT. At data cutoff, all 43 patients were alive, with a median follow-up of 5.0 years (interquartile range 2.4-15.4) and 2 years intervention-free survival (no need for long-term enzyme replacement therapy or allogeneic hematopoietic stem cell transplantation) of 88% (95% confidence interval 78.7-98.4%). Most adverse events/reactions were related to disease background, busulfan conditioning or immune reconstitution; the safety profile of the real world experience was in line with premarketing cohort. One patient from the named patient program developed a T cell leukemia related to treatment 4.7 years after GT and is currently in remission. Long-term persistence of multilineage gene-corrected cells, metabolic detoxification, immune reconstitution and decreased infection rates were observed. Estimated mixed-effects models showed that higher dose of CD34+ cells infused and younger age at GT affected positively the plateau of CD3+ transduced cells, lymphocytes and CD4+ CD45RA+ naive T cells, whereas the cell dose positively influenced the final plateau of CD15+ transduced cells. These long-term data suggest that the risk-benefit of GT in ADA remains favorable and warrant for continuing long-term safety monitoring. Clinical trial registration: NCT00598481 , NCT034786

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Amygdala and hippocampal activation in emotional imagery

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Emotional Memory and Amygdala Activation

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Dimensional distress and orbitofrontal thickness in anxiety patients

Thickness of the medial orbitofrontal cortex (mOFC) was assessed as it varied with reported symptoms of anxiety and depression in a large sample of anxiety patients. A principal component analysis identified a primary factor of transdiagnostic dimensional distress that predicted 24% of the mOFC variance. Severity of distress symptomology was associated with thinning of the mOFC in both hemispheres for both men and women, regardless of the primary DSM diagnosis. Taken together, the data indicate that mOFC thickness might be useful as an objective measure of disorder severity as well as to assess pharmacological or psychological treatment outcome

Narrative imagery: Emotional modulation in the default mode network

none3siThe default mode network (DMN) is activated when constructing and imagining narrative events, with functional brain activity in the medial-prefrontal cortex hypothesized to be modulated during emotional processing by adding value (or pleasure) to the episodic representation. However, since enhanced reactivity during emotional, compared to neutral, content is a more frequent finding in both the brain and body in physiological, neural, and behavioral measures, the current study directly assesses the effects of pleasure and emotion during narrative imagery in the DMN by using a within-subject design to first identify the DMN during resting state and then assess activation during pleasant, neutral, or unpleasant imagery. Replicating previous findings, enhanced functional activity in the medial prefrontal cortex was found when imagining pleasant, compared to unpleasant, events. On the other hand, emotion-related activation was found when imagining either pleasant or unpleasant, compared to neutral, events in other nodes of the DMN including the posterior cingulate cortex (PCC), angular gyrus, anterior hippocampus, lateral temporal cortex, temporal pole, dorsomedial prefrontal cortex (dmPFC), and ventrolateral prefrontal cortex (vlPFC). Pervasive emotional modulation in the DMN is consistent with the view that a primary function of event retrieval and construction is to remember, recreate, and imagine motivationally relevant events important for planning adaptive behavior.mixedSambuco N.; Bradley M.M.; Lang P.J.Sambuco N.; Bradley M.M.; Lang P.J

Imagery, emotion, and bioinformational theory: From body to brain

The bioinformational theory of emotional imagery is a model of the hypothetical mental representations activated when people imagine emotionally engaging events, and was initially proposed to guide research and practice in the use of imaginal exposure as a treatment for fear and anxiety (Lang, 1979). In this 50 year overview, we discuss the development of bioinformational theory and its impact on the study of psychophysiology and psychopathology, most importantly assessing its viability and predictions in light of more recent brain-based studies of neural functional activation. Bioinformational theory proposes that narrative imagery, typically cued by language scripts, activates an associative memory network in the brain that includes stimulus (e.g., agents, contexts), semantic (e.g., facts and beliefs) and, most critically for emotion, response information (e.g., autonomic and somatic) that represents relevant real-world coping actions and reactions. Psychophysiological studies in healthy and clinical samples reliably find measurable response output during aversive and appetitive narrative imagery. Neuroimaging studies confirm that emotional imagery is associated with significant activation in motor regions of the brain, as well as in regions implicated in episodic and semantic memory retrieval, supporting the bioinformational view that narrative imagery prompts mental simulation of events that critically includes the actions and reactions engaged in emotional contexts

Hippocampal and amygdala volumes vary with transdiagnostic psychopathological dimensions of distress, anxious arousal, and trauma

Reduced hippocampal and/or amygdala volumes have been reported in patients with a variety of different anxiety diagnoses, suggesting that structural alterations may vary transdiagnostically across the internalizing disorders. The current study measured hippocampal and amygdala volumes in anxiety and mood disorder patients assessing differences that vary dimensionally with transdiagnostic factors of distress, anxious arousal, and trauma, based on a principal components analysis of questionnaires relating to symptomology. High-resolution structural images were collected in a sample of 165 patients, and volumes extracted from the hippocampal formation (including CA1, CA2/3, CA4/DG, subiculum, and molecular layer) and the amygdala. Transdiagnostically, increasing distress was associated with reduced hippocampal CA1 volume, increasing anxious arousal was associated with reduced hippocampal CA4/DG volume, and increasing trauma severity was associated with reduced amygdala volume in women. Taken together, the data indicate that subcortical brain volumes decrease as the severity of transdiagnostic psychopathological symptomology increases

Neural correlates of repeated retrieval of emotional autobiographical events

none3siUnderstanding the neural correlates of repetitive retrieval of emotional events is critical in addressing pathological emotional processing, as repeated processing is central for a number of different therapeutic interventions. In the current study, single-trial functional brain activity was assessed in key regions implicated in episodic retrieval, including the medial prefrontal cortex (mPFC), anterior hippocampus, posterior hippocampus, and the posteromedial parietal cortex (i.e., posterior cingulate cortex and the precuneus) following repeated retrieval of pleasant and unpleasant autobiographical events. Replicating previous studies, repetition prompted reduced blood-oxygen-level-dependent (BOLD) amplitude in the anterior hippocampus and the mPFC, but not in the posterior hippocampus, due to no functional activity during mental imagery, or in the posteromedial parietal cortex, due to enhanced activation that was sustained across repetitions. Neural activation during pleasant and unpleasant autobiographical retrieval did not differ as a function of repetition, indicating similar processing effects regardless of motivational relevance. Taken together, the hedonic valence of retrieved memories does not affect functional activity associated with repeated retrieval of episodic events, in which the pattern of BOLD amplitude change suggests a dissociation between the hippocampal-prefrontal circuit, which shows repetition suppression, and the posteromedial parietal cortex, which shows sustained activation.mixedBradley M.M.; Sambuco N.; Lang P.J.Bradley M.M.; Sambuco N.; Lang P.J