Longitudinal Phase-Space Manipulation with Beam-Driven Plasma Wakefields.

The development of compact accelerator facilities providing high-brightness beams is one of the most challenging tasks in the field of next-generation compact and cost affordable particle accelerators, to be used in many fields for industrial, medical, and research applications. The ability to shape the beam longitudinal phase space, in particular, plays a key role in achieving high-peak brightness. Here we present a new approach that allows us to tune the longitudinal phase space of a high-brightness beam by means of plasma wakefields. The electron beam passing through the plasma drives large wakefields that are used to manipulate the time-energy correlation of particles along the beam itself. We experimentally demonstrate that such a solution is highly tunable by simply adjusting the density of the plasma and can be used to imprint or remove any correlation onto the beam. This is a fundamental requirement when dealing with largely time-energy correlated beams coming from future plasma accelerators.

PATRI, a Genomics Data Integration Tool for Biomarker Discovery.

The availability of genomic datasets in association with clinical, phenotypic, and drug sensitivity information represents an invaluable source for potential therapeutic applications, supporting the identification of new drug sensitivity biomarkers and pharmacological targets. Drug discovery and precision oncology can largely benefit from the integration of treatment molecular discriminants obtained from cell line models and clinical tumor samples; however this task demands comprehensive analysis approaches for the discovery of underlying data connections. Here we introduce PATRI (Platform for the Analysis of TRanslational Integrated data), a standalone tool accessible through a user-friendly graphical interface, conceived for the identification of treatment sensitivity biomarkers from user-provided genomics data, associated with information on sample characteristics. PATRI streamlines a translational analysis workflow: first, baseline genomics signatures are statistically identified, differentiating treatment sensitive from resistant preclinical models; then, these signatures are used for the prediction of treatment sensitivity in clinical samples, via random forest categorization of clinical genomics datasets and statistical evaluation of the relative phenotypic features. The same workflow can also be applied across distinct clinical datasets. The ease of use of the PATRI tool is illustrated with validation analysis examples, performed with sensitivity data for drug treatments with known molecular discriminants.

Deficits in temporal processing correlate with clinical progression in Huntington's disease.

OBJECTIVES: Precise temporal performance is crucial for several complex tasks. Time estimation in the second-to-minutes range-known as interval timing-involves the interaction of the basal ganglia and the prefrontal cortex via dopaminergic-glutamatergic pathways. Patients with Huntington's disease (HD) present deficits in cognitive and motor functions that require fine control of temporal processing. The objective of the present work was to assess temporal cognition through a peak-interval time (PI) production task in patients with HD and its potential correlation with the Unified Huntington's Disease Rating Scale (UHDRS). MATERIALS AND METHODS: Patients with molecular diagnosis of HD and controls matched by age, sex and educational level (n=18/group) were tested for interval timing in short- (3 seconds), medium- (6 seconds) and long (12 seconds)-duration stimuli. RESULTS: Significant differences were observed in the PI task, with worse performance in HD compared to controls. Patients underestimated real time (left-shifted Peak location) for 6- and 12-second intervals (P<.05) and presented decreased temporal precision for all the intervals evaluated (P<.01). Importantly, a significant correlation was found between time performance and the UHDRS (P<.01). Patients' responses also deviated from the scalar property. CONCLUSIONS: Our results contribute to support that timing functions are impaired in HD in correlation with clinical deterioration. Recordings of cognitive performance related to timing could be a potential useful tool to measure the neurodegenerative progression of movement disorder-related pathologies.

The efficacy of shortening the dosing interval to once every six weeks in Crohn's patients losing response to maintenance dose of infliximab.

BACKGROUND: Patients treated with infliximab for Crohn's disease (CD) frequently require intensified dosage due to loss of response. There are scant data regarding the efficacy of shortening the dosing interval to 6 weeks. AIM: We sought to investigate the efficacy of a once every 6 weeks' strategy compared with dose-doubling. METHODS: This work was a multicentre retrospective study of infliximab-treated CD patients who required dose escalation. The clinical outcome of patients treated by intensification to 5 mg/kg/6 weeks (6-week group) was compared with the outcome of patients whose infliximab was double-dosed (10 mg/kg/8 weeks or 5 mg/kg/4 weeks). RESULTS: Ninety-four patients (mean age: 29.8 years) were included in the study, 55 (59%) in the 6-week group and 39 (41%) in the double-dose group. Demographics and disease characteristics were similar between the two groups, although patients with re-emerging symptoms 5-7 weeks postinfusion were more likely to receive 5 mg/kg/6 weeks dosing (OR: 3.4, 95% CI: 1.4-8.8, P < 0.01). Early response to dose-intensification occurred in 69% of patients in the 6-week group and 67% in the double-dose group (P = N.S.). Regained response was maintained for 12 months in 40% compared with 29% of the patients respectively (P = N.S.). CONCLUSION: In CD patients who lost response to standard infliximab dose, especially when symptoms re-emerge 5-7 weeks postinfusion, shortening the dosing interval to 6 weeks appears to be at least as effective as doubling the dose to 10 mg/kg or halving the infusion intervals to once in 4 weeks.

[Evaluation of a test for rapid detection of D-dimers for the exclusion of the diagnosis of venous thrombosis]. / Evaluation d'un test de détection rapide des D-dimères pour l'exclusion du diagnostic de thrombose veineuse.

OBJECTIVES: The SimpliRED whole blood D-dimer assay for exclusion of deep venous thrombosis in symptomatic outpatient appears to be a simple and rapid method; we wanted to confirm its reliability. METHODS: Fifty consecutive outpatients (mean age 57, range 20 to 89) referred to our department between September and December 1996, for clinically suspected deep venous thrombosis (DVT) were included. Hospitalized patients were excluded as well as patients under anticoagulant and pregnant women. DVT was diagnosed with our usual strategy of compression ultrasonography at the levels of the common femoral, the superficial femoral and the popliteal veins including the exploration of sural and saphenous veins. The D-dimer assay was performed, according to the manufacturer recommendation, blindly by a physician unaware of the results of ultrasonography within one hour. RESULTS: Eight of nineteen patients with DVT had a normal D-dimer test result Four had a sural DVT, but four had a proximal DVT. Furthermore four patients with normal D-dimers had superficial venous thrombosis. CONCLUSIONS: Our series does not confirm the high sensitivity and negative predictive value reported previously. To date it is premature to propose this assay as a first line test in the therapeutic management of patients with suspected DVT.

Native and gamma radiolysis-oxidized lipoprotein(a) increase the adhesiveness of rabbit aortic endothelium.

Accumulation of monocyte-derived foam cells in the arterial intima is a major event in the development of atherogenesis. We have examined whether native and oxidized lipoprotein(a) (Lp(a)) can induce adhesion of monocytic cells to aortic endothelium. The extensive oxidation of paired samples of Lp(a) and low-density lipoprotein (LDL) was achieved by O2.-/OH. free radicals produced by gamma radiolysis of water, leading to similar values for the formation of peroxidation markers (conjugated dienes, TBARS, 8-epi-PGF2alpha) for both Lp(a) and LDL. Rabbit aortic segments were incubated for 5 h in the presence of equimolar concentrations of native and oxidized preparations of Lp(a) and LDL (125 micromol cholesterol/l, corresponding to 40 and 30 mg protein/l for Lp(a) and LDL, respectively). The aortic segments were incubated with rhodamin-isothiocyanate labeled U937 monocytic cells for 30 min and cell adhesion was quantified by fluorescent microscopy. Native Lp(a), and to a larger extent oxidized Lp(a), significantly increased U937 cell adhesion by 2.3 and 2.7 fold compared to controls (P < 0.005 and P < 0.001, respectively). Monocytic cell adhesion was also increased by native LDL (1.6 fold, P < 0.005), and to a greater extent by oxidized LDL (2.3 fold, P < 0.001). Thus native Lp(a) enhances the adhesive properties of the arterial endothelium which may account for its proatherogenic action. Furthermore, our results show that oxidized Lp(a), as well as oxidized LDL, are potent stimuli of monocyte adhesion to endothelial cells.

Sprotte needle for intrathecal anaesthesia for caesarean section: incidence of postdural puncture headache.

Caesarean section was performed under spinal anaesthesia in 55 women using a 25-gauge diamond-tipped needle and in a further 55 mothers with a 24-gauge Sprotte needle. Eight patients (14.5%) developed a headache in the former group, five of whom required a blood patch. There were no headaches reported in the Sprotte group.

[Hemodynamic changes during celioscopy: a study carried out using thoracic electric bioimpedance]. / Modifications hemodynamiques durant la coelioscopie: étude menée par bioimpédance électrique thoracique.

In 18 women A.S.A. physical status 1, a noninvasive thoracic electrical bioimpedance method was used to evaluate haemodynamic changes during gynaecological laparoscopy. A significant decrease in cardiac index was observed after peritoneal insufflation, from 3.2 to 2.8 L.min-1.m-2 and returned to the initial values after ten minutes of Trendelenburg's position. Elevated intra-abdominal pressure was also associated with a significant increase in mean arterial pressure (from 68 to 88 mmHg) and systemic vascular resistance index (from 1620 to 2491 dyn.s.cm-5.m-2). However, values were not restored after peritoneal exsufflation: systemic vascular resistance index values remained 30 per cent higher than that before insufflation. Decreased venous return may account for the significant decrease in cardiac output but mechanical compression does not explain the persistent elevation of systemic vascular resistance.

Modifications hemodynamiques durant la cœlioscopie: étude menée par bioimpédance électrique thoracique.

Au cours de 18 cœlioscopies chez des jeunes femmes A.S.A. status physique 1, les conséquences hémodynamiques du pneumopéritoine et de la position de Trendelenburg ont été évaluées par la méthode non invasive de bioimpédance électrique thoracique. L'index cardiaque chute significativement de 3,2 à 2,8 L · min-1 · m-2 à l'insufflation intra-abdominale et retrouve ses valeurs de départ après dix minutes de Trendelenburg. La pression artérielle moyenne et les résistances vasculaires systémiques indexées sont très augmentées de 1620 à 2491 dyn · s · cm-5 · m-2 après insufflation; l'exsufflation ne permet pas un retour aux valeurs de départ: l'élevation résiduelle des RVSI est de 30 pour cent. L'obstacle au retour veineux pas compression intra-abdominale explique bien la chute du débit cardiaque, conformément aux données de la littérature. En revanche, l'augmentation des résistances vasculaires systémiques ne peut être expliquée par les seuls phénomènes mécaniques du fait de leur persistance après la levée de la compression. L'hypothèse de l'intervention d'un médiateur humoral doit done être discutée.In 18 women A.S.A. physical status 1, a noninvasive thoracic electrical bioimpedance method was used to evaluate haemodynamic changes during gynaecologycal laparoscopy. A significant decrease in cardiac index was observed after peritoneal insufflation, from 3.2 to 2.8 L · min-1 · m-2 and returned to the initial values after ten minutes of Trendelenburg's position. Elevated intra-abdominal pressure was also associated with a significant increase in mean arterial pressure (from 68 to 88 mmHg) and systemic vascular resistance index (from 1620 to 2491 dyn · s · cm-5 · m-2). However, values were not restored after peritoneal exsufflation: systemic vascular resistance index values remained 30 per cent higher than that before insufflation. Decreased venous return may account for the significant decrease in cardiac output but mechanical compression does not explain the persistent elevation of systemic vascular resistance.

Adventitial cysts of the popliteal artery.

Adventitial cysts of the popliteal artery are rare. Their pathogenesis is debated. In one of the two cases reported here, there was a communication between the arterial cyst and the articulation of the knee. This supports the embryonic theory that the articular synovium and adventitial cysts have the same mesenchymal origins. Treatment is surgical, with simple evacuation of the contents of the cyst in uncomplicated cases, excision and reconstruction in the others.

[Hemodynamic changes caused by laparotomy during aorto-iliac surgery]. / Variations hémodynamiques induites par la laparotomie en chirurgie aorto-iliaque.

A haemodynamic study was carried out on 53 patients undergoing elective surgery of the abdominal aorta in order to assess the haemodynamic changes consequent to abdominal manipulations prior to aortic clamping. Surgery was carried out under general anaesthesia and ventilation was controlled. The following parameters were monitored: mean arterial pressure (Pa), cardiac index (CI), systolic index (SI), systemic vascular resistances (Rsa), pulmonary vascular resistances (Rpa), heart rate (fC). Cutaneous circulation was monitored using a photoplethysmographic transducer. The following haemodynamic pattern was seen as the peritoneal cavity was opened and traction on the mesentery was applied: CI +40.7%; fC +28.61%; SI +9.85%; Rsa -39.16%; Rpa -28.43%; Pa -15.7%. The recording of the facial cutaneous photoplethysmographic wave showed an increase of 50%. In some extreme cases, a state of cardiovascular collapse with marked cutaneous erythema strongly resembling anaphylactic shock ensued. The physiopathology of these cardiovascular reactions is unclear, but the haemodynamic pattern as well as the cutaneous vasodilation suggest a stimulation of both vagal and sympathetic nervous systems and the release of vasoactive substances into the general circulation.