Lactate levels affect motor performance in MD 1

Myotonic Dystrophy type 1 (DM1) is a dominantly inherited disease comprehending multiple features. Fatigue and exhaustion during exercise often represent significant factors able to negatively influence their compliance to rehabilitation programs. Mitochondrial abnormalities and a significant increase in oxidative markers, previously reported, suggest the hypothesis of a mitochondrial functional impairment. The study aims at evaluating oxidative metabolism efficiency in 18 DM1 patients and in 15 healthy subjects, through analysis of lactate levels at rest and after an incremental exercise test. The exercise protocol consisted of a submaximal incremental exercise performed on an electronically calibrated treadmill, maintained in predominantly aerobic condition. Lactate levels were assessed at rest and at 5, 10 and 30 minutes after the end of the exercise. The results showed early exercise-related fatigue in DM1 patients, as they performed a mean number of 9 steps, while controls completed the whole exercise. Moreover, while resting values of lactate were comparable between the patients and the control group (p=0.69), after the exercise protocol, dystrophic subjects reached higher values of lactate, at any recovery time (p<0,05). These observations suggest an early activation of anaerobic metabolism, thus evidencing an alteration in oxidative metabolism of such dystrophic patients. As far as intense aerobic training could be performed in DM1 patients, in order to improve maximal muscle oxidative capacity and blood lactate removal ability, then, this safe and validate method could be used to evaluate muscle oxidative metabolism and provide an efficient help on rehabilitation programs to be prescribed in such patients

Is disorganized schizophrenia a predictor of treatment resistance? Evidence from an observational study

Objective: To investigate whether inpatients with disorganized schizophrenia are more resistant to treatment. Method: Eighty-five inpatients were assessed at admission and at discharge for schizophrenia subtype, symptom severity, and treatment resistance criteria. Results: Disorganized patients were significantly more treatment-resistant than paranoid patients (60%, p = 0.001), and presented worse scores on the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI-S), and the Global Assessment of Functioning Scale (GAF) (p < 0.001). Although the difference was not significant, 80% of treatment-resistant patients with disorganized schizophrenia responded to clozapine. Conclusion: Patients with the disorganized subtype of schizophrenia should benefit from clozapine as a second-line agent.Universidade Federal de São Paulo (UNIFESP) Schizophrenia ProgramAssociação Paulista para o Desenvolvimento da Medicina (SPDM) Hospital das Clínicas Luzia de Pinho Melo Department of PsychiatryUNIFESP Interdisciplinary Laboratory of Clinical NeurosciencesSão José do Rio Preto Medical School Department of Psychiatry and Medical PsychologyUNIFESP, Schizophrenia ProgramUNIFESP, Interdisciplinary Laboratory of Clinical NeurosciencesSciEL

Estimulação magnética transcraniana de repetição associada a antidepressivo: início e intensidade da resposta antidepressiva

OBJECTIVE: Transcranial magnetic stimulation has been developed as a noninvasive method to stimulate the cortex, and the treatment of depression is one of its potential therapeutic applications. This report makes a review about add-on trials (hf-rTMS plus antidepressants) discuss whether rTMS does accelerate the onset of action, and increase the therapeutic effects of antidepressants. METHOD: The authors review controlled studies of nonconvulsive rTMS therapy for depression associated with antidepressants. In addition, the authors presented a randomized, double-blind, unicentric trial performed at Institute of Psychiatry of Faculty of Medicine of University of São Paulo with patients meeting DSM-IV criteria for non-psychotic severe depressive episode in order to assess if hf-rTMS augments and accelerates the onset of action of amytriptiline. RESULTS: Most data support an antidepressant effect of high-frequency repetitive TMS administered to the left prefrontal cortex. The absence of psychosis might predict treatment success. Technical parameters possibly affecting treatment success include intensity and duration of treatment, but these suggestions require systematic testing. CONCLUSIONS: rTMS shows promise as a novel antidepressant treatment. Systematic and large-scale studies are needed to identify patient populations most likely to benefit and treatment parameters most likely to produce success. In addition to its potential clinical role, TMS promises to provide insights into the pathophysiology of depression through research designs in which the ability of rTMS to alter brain activity is coupled with functional neuroimaging.OBJETIVOS: Avaliar diferentes estudos que analisam o grau de eficácia da resposta antidepressiva entre a associação de estimulação magnética transcraniana de repetição (EMTr) com antidepressivos em pacientes deprimidos graves. MÉTODOS: Os autores revisaram vários estudos em que a EMTr foi usada concomitantemente a antidepressivos em pacientes deprimidos graves. Adicionalmente, relatou-se um estudo feito no Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Estudo duplo-cego, randomizado, unicêntrico, placebo-controlado com 46 pacientes atendendo aos critérios diagnósticos da DSM-IV para episódio depressivo severo. Os pacientes estavam em uso de amitriptilina. RESULTADOS: De forma geral, a maioria dos estudos mostra que a EMTr apresenta boa eficácia antidepressiva quando associada a antidepressivos. Há grande diversidade de parâmetros técnicos utilizados, tipos de bobina, diferentes técnicas de placebo e uso de diferentes antidepressivos. O estudo realizado no Instituto de Psiquiatria mostrou que o emprego da EMTr de alta freqüência aumentou a resposta antidepressiva à amitriptilina e diminuiu o tempo para o início da resposta antidepressiva em relação ao grupo placebo. CONCLUSÕES: EMTr é um método novo, promissor e com grande potencial para o tratamento da depressão. Apesar disso, observa-se que não há ainda uniformidade no emprego dos parâmetros técnicos, nem tampouco das técnicas de placebo. O estudo realizado no Instituto de Psiquiatria do HC- FMUSP mostrou grandes taxas de resposta e remissão em relação ao grupo com estimulação sham e amitriptilna

The Emergence of Emotions

Emotion is conscious experience. It is the affective aspect of consciousness. Emotion arises from sensory stimulation and is typically accompanied by physiological and behavioral changes in the body. Hence an emotion is a complex reaction pattern consisting of three components: a physiological component, a behavioral component, and an experiential (conscious) component. The reactions making up an emotion determine what the emotion will be recognized as. Three processes are involved in generating an emotion: (1) identification of the emotional significance of a sensory stimulus, (2) production of an affective state (emotion), and (3) regulation of the affective state. Two opposing systems in the brain (the reward and punishment systems) establish an affective value or valence (stimulus-reinforcement association) for sensory stimulation. This is process (1), the first step in the generation of an emotion. Development of stimulus-reinforcement associations (affective valence) serves as the basis for emotion expression (process 2), conditioned emotion learning acquisition and expression, memory consolidation, reinforcement-expectations, decision-making, coping responses, and social behavior. The amygdala is critical for the representation of stimulus-reinforcement associations (both reward and punishment-based) for these functions. Three distinct and separate architectural and functional areas of the prefrontal cortex (dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex) are involved in the regulation of emotion (process 3). The regulation of emotion by the prefrontal cortex consists of a positive feedback interaction between the prefrontal cortex and the inferior parietal cortex resulting in the nonlinear emergence of emotion. This positive feedback and nonlinear emergence represents a type of working memory (focal attention) by which perception is reorganized and rerepresented, becoming explicit, functional, and conscious. The explicit emotion states arising may be involved in the production of voluntary new or novel intentional (adaptive) behavior, especially social behavior

Search for the direct production of charginos and neutralinos in final states with tau leptons in √s=13 TeV collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with at least two hadronically decaying tau leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of 36.1 fb−1, recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13TeV.Nosignificant deviation from the expected Standard Model background is observed. Limits are derived in scenarios of ˜χ+1 ˜χ−1 pair production and of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 production in simplified models where the neutralinos and charginos decay solely via intermediate left-handed staus and tau sneutrinos, and the mass of the ˜ τL state is set to be halfway between the masses of the ˜χ±1 and the ˜χ01. Chargino masses up to 630 GeV are excluded at 95% confidence level in the scenario of direct production of ˜χ+1 ˜χ−1 for a massless ˜χ01. Common ˜χ±1 and ˜χ02 masses up to 760 GeV are excluded in the case of production of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 assuming a massless ˜χ01. Exclusion limits for additional benchmark scenarios with large and small mass-splitting between the ˜χ±1 and the ˜χ01 are also studied by varying the ˜ τL mass between the masses of the ˜χ±1 and the ˜χ01

Search for supersymmetry in events with b-tagged jets and missing transverse momentum in pp collisions at √s = 13 TeV with the ATLAS detector

A search for the supersymmetric partners of the Standard Model bottom and top quarks is presented. The search uses 36.1 fb−1 of pp collision data at √s = 13 TeV collected by the ATLAS experiment at the Large Hadron Collider. Direct production of pairs of bottom and top squarks (b˜1 and t˜1) is searched for in final states with b-tagged jets and missing transverse momentum. Distinctive selections are defined with either no charged leptons (electrons or muons) in the final state, or one charged lepton. The zero-lepton selection targets models in which the b˜1 is the lightest squark and decays via b˜1 → bχ˜01 , where ˜χ01 is the lightest neutralino. The one-lepton final state targets models where bottom or top squarks are produced and can decay into multiple channels, b˜1 → bχ˜01 and b˜1 → tχ˜±1, or t˜1 → tχ˜01 and t˜1→ bχ˜±1, where ˜χ±1 is the lightest chargino and the mass difference mχ˜±1 − mχ˜01 is set to 1 GeV. No excess above the expected Standard Model background is observed. Exclusion limits at 95% confidence level on the mass of third-generation squarks are derived in various supersymmetry-inspired simplified models

Search for direct top squark pair production in final states with two leptons in √s=13 TeV pp collisions with the ATLAS detector

The results of a search for direct pair production of top squarks in events with two opposite-charge leptons (electrons or muons) are reported, using 36.1 fb−1 of integrated luminosity from proton–proton collisions at √s=13 TeV collected by the ATLAS detector at the Large Hadron Collider. To cover a range of mass differences between the top squark t~ and lighter supersymmetric particles, four possible decay modes of the top squark are targeted with dedicated selections: the decay t~→bχ~1± into a b-quark and the lightest chargino with χ~1±→Wχ~10 , t~→tχ~10 into an on-shell top quark and the lightest neutralino, the three-body decay t~→bWχ~10 and the four-body decay t~→bℓνχ~10. No significant excess of events is observed above the Standard Model background for any selection, and limits on top squarks are set as a function of the t~ and χ~01 masses. The results exclude at 95% confidence level t~ masses up to about 720 GeV, extending the exclusion region of supersymmetric parameter space covered by previous searches

Search for direct top squark pair production in final states with two leptons in √s = 13 TeV pp collisions with the ATLAS detector

The results of a search for direct pair production of top squarks in events with two opposite-charge leptons (electrons or muons) are reported, using 36.1 fb−1 of integrated luminosity from proton–proton collisions at √s = 13 TeV collected by the ATLAS detector at the Large Hadron Collider. To cover a range of mass differences between the top squark t ˜ and lighter supersymmetric particles, four possible decay modes of the top squark are targeted with dedicated selections: the decay t ˜ → bχ˜ ± 1 into a b-quark and the lightest chargino with χ˜ ± 1 → Wχ˜ 0 1 , the decay t ˜ → tχ˜ 0 1 into an on-shell top quark and the lightest neutralino, the three-body decay t ˜ → bWχ˜ 0 1 and the four-body decay t ˜ → bνχ˜ 0 1 . No significant excess of events is observed above the Standard Model background for any selection, and limits on top squarks are set as a function of the t ˜ and χ˜ 0 1 masses. The results exclude at 95% confidence level t ˜ masses up to about 720 GeV, extending the exclusion region of supersymmetric parameter space covered by previous searches

Search for top quark decays t → qH, with H → γγ, in √s = 13 TeV pp collisions using the ATLAS detector

This article presents a search for flavour-changing neutral currents in the decay of a top quark into an up-type (q = c, u) quark and a Higgs boson, where the Higgs boson decays into two photons. The proton-proton collision data set analysed amounts to 36.1 fb−1 at √ s = 13 TeV collected by the ATLAS experiment at the LHC. Top quark pair events are searched for, where one top quark decays into qH and the other decays into bW. Both the hadronic and leptonic decay modes of the W boson are used. No significant excess is observed and an upper limit is set on the t → cH branching ratio of 2.2 × 10−3 at the 95% confidence level, while the expected limit in the absence of signal is 1.6 × 10−3 . The corresponding limit on the tcH coupling is 0.090 at the 95% confidence level. The observed upper limit on the t → uH branching ratio is 2.4 × 10−3

Conceptual Design of a Soft X‐ray SASE‐FEL Source

FELs based on SASE are believed to be powerful tools to explore the frontiers of basic sciences, from physics to chemistry to biology. Intense R&D programs have started in the USA and Europe in order to understand the SASE physics and to prove the feasibility of these sources. The allocation of considerable resources in the Italian National Research Plan (PNR) brought about the formation of a CNR‐ENEA‐INFN‐University of Roma "Tor Vergata" study group. A conceptual design study has been developed and possible schemes for linac sources have been investigated, bringing to the SPARX proposal. We report in this paper the results of a preliminary start to end simulation concerning one option we are considering based on an S‐band normal conducting linac with high brightness photoinjector integrated in a RF compressor