Use of diamond sensors for a high-flux, high-rate X-ray pass-through diagnostic.

X-ray free-electron lasers (XFELs) deliver pulses of coherent X-rays on the femtosecond time scale, with potentially high repetition rates. While XFELs provide high peak intensities, both the intensity and the centroid of the beam fluctuate strongly on a pulse-to-pulse basis, motivating high-rate beam diagnostics that operate over a large dynamic range. The fast drift velocity, low X-ray absorption and high radiation tolerance properties of chemical vapour deposition diamonds make these crystals a promising candidate material for developing a fast (multi-GHz) pass-through diagnostic for the next generation of XFELs. A new approach to the design of a diamond sensor signal path is presented, along with associated characterization studies performed in the XPP endstation of the LINAC Coherent Light Source (LCLS) at SLAC. Qualitative charge collection profiles (collected charge versus time) are presented and compared with those from a commercially available detector. Quantitative results on the charge collection efficiency and signal collection times are presented over a range of approximately four orders of magnitude in the generated electron-hole plasma density.

Academic and professional paths of narcoleptic patients: the Narcowork study.

OBJECTIVE/BACKGROUND: To study educational and professional pathways of narcoleptic patients and examine demographic, disease-related and environmental factors associated with a better academic and professional prognosis. PATIENTS/METHODS: In sum, 69 narcoleptic patients (51 narcolepsy type 1 and 18 narcolepsy type 2, age 42.5 ± 18.2 years) were enrolled in this pilot monocentric cross-sectional study with a comparison group (80 age- and sex-matched controls) between October 2017 and July 2018 in Lyon Center for Sleep Medicine. They completed questionnaires about their academic and professional trajectories and specific scales of quality of life (EuroQol quality of life scale EQ-5D-3L), depression (beck depression inventory, BDI), sleepiness (Epworth Sleepiness Scale, ESS) and narcoleptic symptoms severity (narcolepsy severity scale, NSS). RESULTS: No difference in grade repetition or final obtained diploma was observed between patients and controls, but patients evaluated their academic curricula as more difficult (45.5% vs 16.9%, p = 0.0007), complained for more attentional deficits (75% vs 22.1%, p < 0.0001), and had needed more educational reorientation (28.6% vs 9.9%, p = 0.01). Even if no difference was observed in occupational category and professional status, patients expressed significantly less satisfaction about their work. Patients had more signs of depression [OR severe depression = 4.4 (1.6-12.6), p = 0.02] and their quality of life was significantly decreased (67.3 ± 18.4 vs 80.6 ± 13.2, p = 0.0007) as compared to controls. Multivariate analysis showed that a more favorable professional career was associated with a better quality of life. CONCLUSIONS: Educational and professional pathways do not seem to be significantly impaired in narcoleptic patients, but their experience and quality of life are affected. These findings may allow to reassure patients and should lead to a more comprehensive management of the disease. CLINICAL TRIAL REGISTRATION: Narcowork, https://clinicaltrials.gov/ct2/show/NCT03173378, N° NCT03173378.

Genetic correlations among milk yield, morphology, performance test traits and somatic cells in dual-purpose Rendena breed.

Selection in native local breeds needs great carefulness due to the small population size and the risk of inbreeding. Furthermore, most breeds are dual-purpose, and milk and beef attitudes are antagonistic. For preservation purposes functional traits need to be considered. Focusing on the small local Rendena cattle, this study aimed to analyse the genetic correlations among milk, beef and udder health traits and the response to selection predicted under different scenarios. The study considered milk, fat and protein yields (MY), factor scores for udder volume (UV), conformation (UC) and muscularity obtained from type traits scored on primiparous cows, and performance test traits (PT) measured on young bulls at test station: average daily gain, in vivo SEUROP fleshiness, in vivo dressing percentage. Somatic cell score (SCS) was considered as a functional trait, with a possibility of restricting its genetic gain to zero. The study considered 281 497 MY test-day data collected on 16 974 cows, and data from linear type evaluation on 11 992 primiparous cows for factor scores. The PT data were recorded on 1428 young bulls, and SCS obtained from cell counts at milk recording. Bi-trait restricted maximum likelihood animal model analyses were performed to assess genetic parameters. Heritability varied from 0.157 (fat) to 0.442 (dressing percentage). Udder volume and MY resulted positively genetically correlated (average correlation 0.427), whereas the low-negative genetic correlation between MY and UC (-0.141) suggested a negative impact of milk gain on udder form. Beef traits of factor muscularity and PT showed medium-high favourable genetic correlations (from 0.357 to 0.984), excluding a null correlation between daily gain and muscularity. The genetic correlation MY v. muscularity was unfavourable (-0.328 on average), whereas null correlations were found in MY v. PT, apart from fat v. dressing percentage (-0.151). Somatic cell score showed low unfavourable correlations with protein (0.111) and UV (0.092), and favourable correlations with UC (-0.193). Response to selection in different scenarios indicated a good balanced gain for milk and beef when standardized economic weights of 0.66 and 0.34 are given to the two attitudes, and SCS genetic gain is restricted. Current genetic trends (MY and PT increasing, but muscularity lessening) reflect a stronger selection for milk, suggesting a slight progressive change towards a milk conformation. Aiming to preserve the dual-purpose characteristics of a breed, proper breeding policies taking into account the genetic relationships among traits and including functional traits should be applied in local dual-purpose populations.

VERO® radiotherapy for low burden cancer: 789 patients with 957 lesions.

PURPOSE: The aim of this retrospective study is to evaluate patient profile, feasibility, and acute toxicity of RadioTherapy (RT) delivered by VERO® in the first 20 months of clinical activity. METHODS: Inclusion criteria: 1) adult patients; 2) limited volume cancer (M0 or oligometastatic); 3) small extracranial lesions; 4) treatment between April 2012 and December 2013 and 5) written informed consent. Two techniques were employed: intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT). Toxicity was evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria. RESULTS: Between April 2012 and December 2013, 789 consecutive patients (957 lesions) were treated. In 84% of them one lesion was treated and in 16% more than one lesion were treated synchronously/metachronously; first radiotherapy course in 85%, re-irradiation in 13%, and boost in 2% of cases. The treated region included pelvis 46%, thorax 38%, upper abdomen 15%, and neck 1%. Radiotherapy schedules included <5 and >5 fractions in 75% and 25% respectively. All patients completed the planned treatment and an acceptable acute toxicity was observed. CONCLUSIONS: RT delivered by VERO® was administrated predominantly to thoracic and pelvic lesions (lung and urologic tumours) using hypofractionation. It is a feasible approach for limited burden cancer offering short and well accepted treatment with favourable acute toxicity profile. Further investigation including dose escalation and other available VERO® functionalities such as real-time dynamic tumour tracking is warranted in order to fully evaluate this innovative radiotherapy system.

Factor analysis for genetic evaluation of linear type traits in dual-purpose autochthonous breeds.

Factor analysis was applied to individual type traits (TT) scored in primiparous cows belonging to two dual purpose Italian breeds, Rendena (REN; 20 individual type traits evaluated on 11 399 first parity cows), and Aosta Red Pied (ARP; 22 individual type traits evaluated on 36 168 primiparous cows). Six common latent factors (F1 to F6; eigenvalues ⩾1) which explained 63% (REN) and 58% (ARP) of the total variance were obtained. F1 included TT mainly related to muscularity, and F2 to body size. The F3 and F4 accounted for udder size and conformation, respectively. F5 included rear legs and feet. Biological significance for F6 was not readily obtained. Moderate to low heritability were estimated through REML single-trait analysis from factor scores (from 0.22 to 0.52 in REN, and from 0.08 to 0.37 in ARP). The greatest heritability values were estimated for body size and muscularity (0.52 and 0.37 for body size; and 0.40 and 0.32 for muscularity in REN and ARP, respectively). As expected, rank correlations, obtained considering estimated breeding values derived from best linear unbiased prediction analysis on the individual TT and factor score, showed similar coefficients to those observed in the factor analysis following loading of TT within each latent factor. These results suggest the possibility to implement the factor analysis in the morphological evaluation, simplifying the information given by the type traits into new variables useful for the genetic improvement of dual purpose cattle.

Validation of the Hamilton Rating Scale for Depression in adults with epilepsy.

PURPOSE: Mood disorders represent a frequent psychiatric comorbidity among patients with epilepsy, having a major impact on their quality of life and contributing considerably to the global burden of the disease. The availability of standardized clinical instruments validated in populations with epilepsy has important implications in terms of diagnosis and treatment. This aimed to validate the Hamilton Rating Scale for Depression (HRSD) in adult patients with epilepsy. METHODS: A consecutive sample of 120 adult outpatients with epilepsy was assessed using the Mini International Neuropsychiatric Inventory (MINI) Plus version 5.0.0 and the HRSD. RESULTS: Cronbach's alpha coefficient was 0.824 for the 17-item version and 0.833 for the 21-item version. Receiver operating characteristic analysis showed an area under the curve of 0.896 and 0.899, respectively, for the two versions. However, the HRSD-17 demonstrated the best psychometric properties compared to the HRSD-21 and, with a cutoff score of 6, showed a sensitivity of 94%, a specificity of 80%, a positive predictive value of 46%, and a negative predictive value of 99%. CONCLUSIONS: The HRSD proved to be reliable and valid in the epilepsy setting and will stimulate further research in this area.

Genetic parameters for linear type traits in the Rendena dual-purpose breed.

The aim of the study was to estimate the genetic parameters for five composite traits and 20 individual type traits on 10,735 first-parity Rendena dual-purpose cows. Fixed effects included in the linear animal mixed models were herd-year-classifier, days in milk and age at first calving; the additive genetic effect of the animal was included as a random effect. Heritability estimates varied from 0.12 (feet) to 0.52 (stature). Genetic correlations between the individual body size traits were all ≥0.69; similar strong genetic correlations existed between traits describing similar morphological characteristics (e.g. mammary system, fleshiness). Many of the body size traits were negatively genetically correlated with animal fleshiness. Genetic trends showed that genetic merit for body size increased consistently over the last 10 years, while genetic merit for fleshiness declined. These results suggest that the characteristics of the dual-purpose Rendena cattle are becoming more like specialized milk-producing animals. Nonetheless, sufficient genetic variation exists to halt or reverse the deterioration in fleshiness.

Psychological functioning measures in patients with primary insomnia and sleep state misperception.

OBJECTIVE: Sleep state misperception (SSM) is a term used in the International Classification of Sleep Disorders to indicate people who mistakenly perceive their sleep as wakefulness. SSM is a form of primary insomnia. The aim of this study was to record psychological functioning measures (anxiety, depression, ability to feel pleasure, obsessive-compulsive traits) in a population of patients with primary insomnia and to evaluate the relationship between these measures and the patients' perception of their sleep. MATERIALS AND METHODS: Seventy-six consecutive patients with primary insomnia were enrolled: 34 men and 42 women, mean age 53.9 ± 13.1. Sleep study included the following: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Berlin's Questionnaire and home-based polysomnography. Psychometric evaluation included the following: Self-Administered Anxiety Scale, Beck's Depression Inventory, Maudsley's Obsessive Compulsive Inventory, Snaith-Hamilton Pleasure Scale, Eating Attitude Test. RESULTS: All patients with insomnia had psychometric scores higher than the general population, but very few patients, in both groups, had anxiety or depression scores consistent with severe mood or anxiety disorders. Comparisons between subjective and objective scores confirmed that most sleep parameters were underestimated. Patients with SSM had lower anxiety scores as compared to patients without SSM. CONCLUSIONS: The study did not succeed in identifying any predictor of sleep misperception. We speculate that a group of patients, rather than being extremely worried by their insomnia, may have a sort of agnosia of their sleep.

Omega-3 fatty acids and schizophrenia: evidences and recommendations.

Schizophrenia is a brain disease that represents a not rare condition, in fact the lifetime risk of developing schizophrenia is widely accepted to be around 1 in 100. Schizophrenia clinically manifests with acute episodes which are associated with hallucinations, delirium, behavioral disorders and a variable range of chronic persistent symptoms, which can be debilitating. The causes of schizophrenia are not clearly understood. It seems that genetic factors may produce a vulnerability to schizophrenia, along with environmental factors that contribute in a different way from individual to individual. In this context schizophrenia constitutes the outcome of a complex interaction between multiple genes and environmental risk factors, none of which on its own causes the disorder itself. Antipsychotic medications represent the first line of psychiatric treatment for schizophrenia. But there is a growing body of evidence that omega-3 fatty acids can prevent the disease or at least mitigate the course and symptoms. Probably, an appropriate dietary supplementation can play a partially therapeutic effect, even in more severe patients, improving some behavioral aspects and, mainly, reducing the cognitive deterioration. In this context the role of omega-3 fatty acids as a treatment for schizophrenia will strengthen the thrust of researchers and clinicians to the integrated approach to the prevention and cure of a disease that for more than a century challenging researchers.

Treatment of prurigo nodularis with pregabalin.

WHAT IS KNOWN AND OBJECTIVE: Prurigo nodularis (PN) is a chronic skin condition that is difficult to treat. Pregabalin is one of the possible treatments for PN but its safety and efficacy are not well defined. We aimed to assess the efficacy of pregabalin in patients with PN. METHODS: Thirty patients (10 men, 20 women; mean age 51.6 ± 9.39 years) were treated with pregabalin (75 mg/day) for 3 months. Efficacy was classified as (i) successful (disappearance of the pruritus and reduction of nodules); (ii) slight improvement/reduction of the nodules, that is, number and/or flattening, no disappearance of itching; or (iii) unsuccessful. RESULTS: Twenty-three patients (76%) responded successfully after 3 months of treatment. There was a statistically significant difference between visual analogue scale scores before and after 1 month treatment period (8·15 ± 2·04 and 1·5 ± 1·12, respectively; P < 0·0001). Pregabalin was generally well tolerated with only six (20%) patients reporting side effects. No patient showed any renal insufficiency. WHAT IS NEW AND CONCLUSION: In our study, pregabalin was effective for the treatment of PN. However, given the open and non-controlled study design used, a properly powered randomized controlled validation study is called for.

Pain and sleep: from reaction to action.

Sleep disruption by painful stimuli is frequently observed both in clinical and experimental conditions. Nociceptive stimuli produce significantly more arousals (30% of stimuli) than non-nociceptive ones. However, even if they do not interrupt sleep, they can trigger a variety of other reactions. Reflex behaviours in response to nociceptive stimuli can be observed during all sleep stages, and are more likely to occur in association with an arousal than alone. Cardiac activation represents a robust sympathetically driven effect preserved whatever the state of vigilance, even if its magnitude can be modulated by a concomitant cortical arousal. Not withstanding these reactions, incorporation of nociceptive stimuli into dream content remains limited. At cortical level, laser-evoked potential studies demonstrate that the processing of nociceptive stimulations is partly conserved during all sleep stages. Furthermore, when nociceptive stimulations interrupt sleep, the cortical response presents a late component suggesting that the stimulation has to be cognitively processed in order to produce a subsequent arousal. More complex reactions to nociceptive stimulations were occasionally reported. In this context, an epileptic patient with intracerebral electrodes implanted for therapeutic purposes allowed us extending these observations. This patient exhibited finger lifts in response to stimulations delivered during paradoxical (REM) sleep. This motor reaction was previously used during wakefulness to indicate that the stimulation had been perceived. When these finger lifts occurred a systematic re-activation of the anterior cingulate preceded each movement. This observation suggests that during PS, not only the processing of sensory inputs but also the capacity for the sleeper to intentionally indicate his perception could be preserved under particular circumstances.

Validation of the Italian version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E).

The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was developed for the rapid detection of a major depressive episode in people with epilepsy. It has been proven to be a user-friendly screening instrument. This study describes the development, validation, and psychometric properties of the Italian version of the NDDI-E. A consecutive sample of 120 outpatients with epilepsy has been assessed using the M.I.N.I. Plus version 5.0.0 and the NDDI-E. All patients had no major difficulties in understanding or answering the questions of the Italian version. Cronbach's alpha coefficient was 0.851. Receiver operating characteristic analysis showed an area under the curve of 0.943 (CI95%=0.902-0.985; SE 0.021; p<0.001), a cut off score of 13, a sensitivity of 86.2%, a specificity of 89%, a positive predictive value of 71.4%, and a negative predictive value of 95.3%.

Functional neuroimaging: points of intersection between biology and psychotherapy.

OBJECTIVES: In the evaluation of the biological basis of psychotherapeutic changes many researches have noticed potential effects of psychotherapeutic interventions on the neural correlates of mental illness. In a psychotherapeutic setting, modifications in individual thoughts and feelings can restore brain functioning at physiological levels. This paper gives an overview about neurobiological methods and their potential to support psychotherapy research and to examine psychotherapy effects across a number of psychiatric disorders. METHODS: Relevant informations are identified through searches of MEDLINE and Current Contents/Clinical Medicine. RESULTS: Studies demonstrate that it is important to consider putative neural mechanisms of psychotherapy, changes in the brain associated with psychotherapy on a global and molecular level, intervention-specific effects and prediction of outcome. Pharmacotherapy and psychotherapy converge in a common change of neuronal functions that might be detected by imaging techniques and might resemble correlates of clinical improvement. CONCLUSIONS: Neuroimaging techniques applied to psychotherapy research are relevant for further understanding neurobiological underpinnings of psychotherapy processes and predicting treatment outcome in order to improve clinical decision-making and treatment.

Mood, hormones and quality of life.

In the last years, together with progress of research in psychoneuroendocrinology, there has been growing interest in the psychological aspects of clinical care in endocrine disease. In particular, some issues such as life events preceding disease onset, psychological distress associated with acute illness and convalescence, abnormal illness behaviour and several other aspects of quality of life in endocrinology and mood disorders have received more and more attention. Clinical data on pharmacologic and non pharmacologic interventions that are effective at improving the quality of life for patients with mood disorders and endocrine disturbances is emerging. With the development of more effective treatment options many more patients with mood disorders and endocrine disturbances will achieve healthy levels of functioning and quality of life, which will alleviate the burden that the illness imposes on patients, their families, and caregivers.

Effects of obstructive sleep apnea on cognitive function: a comparison between younger and older OSAS patients.

BACKGROUND AND PURPOSE: Patients with obstructive sleep apnea syndrome (OSAS) present cognitive deficits similar to those observed with aging. The aim of the study was to assess the effects of age on cognitive functions in OSAS patients. It was hypothesized that older OSAS patients will exhibit significant cognitive dysfunction relative to younger OSAS patients and controls. PATIENTS AND METHODS: Younger and older OSAS patients were compared to younger and older control subjects (age cut-off set at 50 yrs). Participants underwent a polysomnographic (PSG) and neuropsychological evaluation. Variables were analyzed by two-way analyses of variance (ANOVAs) with two factors: Group (control and OSAS) and Age (younger and older). Additionally, we evaluated the contribution of attentional deficits to cognitive dysfunction for each subgroup of patients by using Spearman correlation coefficients. RESULTS: No Group-by-Age interaction was found for any neuropsychological variables (p<0.05). However, main Group and Age effects were found. Correlations indicated that attentional deficits contributed importantly to a poorer cognitive performance in younger OSAS patients only (p<0.01). CONCLUSIONS: Our results are in agreement with those of the literature for both OSAS-related and aging-related cognitive deficits but did not demonstrate that age interacts with the effects of the OSAS condition to make those cognitive deficits worse.

Alzheimer disease: primary ischemia concept and promising therapy.

The important role of cerebral blood flow (CBF) in Alzheimer disease (AD) has been increasingly recognized in recent years. An abundance of data (The Rotterdam Study, see text) has shown the decline of CBF velocity with transcranial Doppler, confirming earlier data obtained with the xenon133 method. In spite of these data, AD is still considered a neurodegenerative disorder with secondary CBF changes. This work is a critical evaluation of earlier literature because of cogent reasons for the adoption of a new concept of AD as a primary ischemic disorder. Reports of lacking correlation between severity of CBF defi cit and degree of tissue damage or clinical fi ndings serve as evidence for primary ischemia because of the incompatibility with the concept of secondary ischemia.The CBF defi cit is thought to be due to the human upright gait in here dopredisposed individuals. As to therapy and prevention, a very simple, cheap and promising treatment is suggested (head-down-therapy).