The evolution of the ISOLDE control system

The ISOLDE on-line mass separator facility is operating on a Personal Computer based control system since spring 1992. Front End Computers accessing the hardware are controlled from consoles running Microsoft WindowsTM through a Novell NetWare4TM local area network. The control system is transparently integrated in the CERN wide office network and makes heavy use of the CERN standard office application programs to control and to document the running of the ISOLDE isotope separators. This paper recalls the architecture of the control system, shows its recent developments and gives some examples of its graphical user interface

Primary leptomeningeal plasmablastic lymphoma

Lymphomas that develop in human immunodeficiency virus (HIV) infected patients are predominantly aggressive B-cells lymphomas. The most common HIV-associated lymphomas include Burkitt lymphoma, diffuse large B-cell lymphoma (that often involves the CNS), primary effusion lymphoma, and plasmablastic lymphoma (PBL). Of these, PBL is relatively uncommon and displays a distinct affinity for presentation in the oral cavity. In this manuscript we report a previously undescribed primary leptomeningeal form of PBL in a patient with acquired immunodeficiency syndrome. A 40-year-old HIV positive man presented with acute onset confusion, emesis, and altered mental status. Lumbar puncture showed numerous nucleated cells with atypical plasmocyte predominance. CSF flowcytometry showed kappa restriction with CD8 and CD38 positivity and negative lymphocyte markers, while the MRI showed diffuse leptomeningeal enhancement. As the extensive systemic work-up failed to reveal any disease outside the brain, an en bloc diagnostic brain and meningeal biopsy was performed. The biopsy specimen showed sheets of plasmacytoid cells with one or more large nuclei, prominent nuclear chromatin, scattered mitoses, and abundant cytoplasm, highly suggestive of plasmablastic lymphoma. HIV-associated malignancies have protean and often confusing presentations, which pose diagnostic difficulties posed to the practicing neurological-surgeons. Even in cases where an infectious cause is suspected for the meningeal enhancement, neoplastic involvement should be considered, and cytology and flow-cytometry should be routinely ordered on the CSF samples

Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state

Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 ± 7 mL (mean ± SEM) of resting water. Upon drinking, the gastric fluid rose to 242 ± 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T50%) of 13 ± 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 ± 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 ± 24 mL contained within 15 ± 2 pockets of 6 ± 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 ± 15 mL distributed into 16 ± 3 pockets of 5 ± 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds

Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

The effect of arabinoxylooligosaccharides on upper gastroduodenal motility and hunger ratings in humans

BACKGROUND AND AIMS: Prebiotics such as Arabinoxylooligosaccharides (AXOS) are non-digestible, fermentable food ingredients stimulating growth/activity of colonic bacteria with enhanced carbohydrates fermentation (CF) in humans. The migrating motor complex (MMC) of the gastrointestinal tract has been recently identified as an important hunger signal, but no data are available yet on the role of acute CF on MMC activity and related hunger ratings. Thus, we aimed to study the effect of acute AXOS CF on MMC and hunger in humans. METHODS: A total of 13 healthy volunteers were randomized in a single-blind crossover placebo-controlled study where 9.4 g of AXOS or 10 g of maltodextrin and 1 g of unlabelled lactose ureide (LU) were given 12 hours prior to the study and, in the next morning, together with a pancake containing 500 mg of 13 C-LU. In 10 hours after the meal, 13 CO2 and hydrogen excretion were determined every 15 minutes while hunger/appetite ratings every 2 minutes through a VAS questionnaire. Five hours after the meal, antroduodenal motility was measured using HRM. KEY RESULTS: AXOS significantly increased CF (158 ± 81 vs 840 ± 464 H2 ppm*minute, placebo vs AXOS, P < .05) without affecting the orocecal transit time (OCTT). AXOS had no significant effect on the occurrence, origin, and duration of phase III and on the total number, origin, and duration of phases I and II. Hunger and appetite scores prior and after phase III were not affected by AXOS. CONCLUSIONS: AXOS acutely increases colonic fermentation, but this neither affects OCTT, activity of the MMC, nor interdigestive hunger scores in man.status: publishe

Motilin-induced gastric contractions signal hunger in man

Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin.status: publishe