CBETA: First Multipass Superconducting Linear Accelerator with Energy Recovery.

Energy recovery has been achieved in a multipass linear accelerator, demonstrating a technology for more compact particle accelerators operating at higher currents and reduced energy consumption. Energy delivered to the beam during the first four passes through the accelerating structure was recovered during four subsequent decelerating passes. High-energy efficiency was achieved by the use of superconducting accelerating cavities and permanent magnets. The fixed-field alternating-gradient optical system used for the return loop successfully transported electron bunches of 42, 78, 114, and 150 MeV in a common vacuum chamber. This new kind of accelerator, an eight-pass energy recovery linac, has the potential to accelerate much higher current than existing linear accelerators while maintaining small beam dimensions and consuming much less energy per electron.

Non-persistence in ischaemic stroke: Risk of recurrent vascular events.

OBJECTIVES: Ischaemic stroke is one of the leading causes of death and disability worldwide. Although the secondary preventive medication should be continued for life, its use commonly declines in time. This may lead to recurrent vascular events. In this study, we investigated if during a long follow-up period discontinuation of medication (non-persistence) in real life ischaemic stroke patients increased the risk of recurrent vascular events. MATERIALS AND METHODS: This was a retrospective cohort study with the data retrieved from a database and the original patient records. The occurrence of new vascular events was determined from the electronic medical record. Medication use at time of follow-up was ascertained using the pharmacy-link in the electronic medical file and through a telephone interview. Primary endpoint was recurrent vascular events. Patients with two or more vascular risk factors were considered as having a high-risk profile. RESULTS: A total of 286 patients (persistent n = 182 and non-persistent n = 104) were included. After median follow-up period of 5½ years in the persistent group 14.8% had a recurrent vascular event, vs 23.1% in the non-persistent group (P = .801). In the patients with a high-risk profile, the persistent group had significantly less recurrent vascular events than the non-persistent group (23.5% against 46.4% P = .021). CONCLUSION: After a long follow-up period, ischaemic stroke patients with a high vascular risk profile who stopped taking their secondary preventive medication had an increased risk of a recurrent vascular events.

Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial.

IMPORTANCE: Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. OBJECTIVE: To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT. DESIGN, SETTING, AND PARTICIPANTS: The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015. MAIN OUTCOMES AND MEASURES: Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion. RESULTS: Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours. CONCLUSION AND RELEVANCE: For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion. TRIAL REGISTRATION: trialregister.nl Identifier: NTR1804.

Comparison of glycopyrrolate and atropine in ameliorating the adverse effects of imidocarb dipropionate in horses.

REASONS FOR PERFORMING STUDY: Imidocarb, an effective treatment for piroplasmosis, may cause colic and diarrhoea in horses. Atropine and glycopyrrolate are anticholinergics that could reduce the adverse effects of imidocarb. However, atropine and glycopyrrolate inhibit gastrointestinal motility, potentially causing ileus and colic. OBJECTIVES: To compare glycopyrrolate and atropine in ameliorating the adverse effects of imidocarb dipropionate in horses and to determine the effect of combinations of these drugs on the gastrointestinal tract. METHODS: A blinded, randomised, crossover study was performed in 8 healthy horses. Each horse received 0.9% saline i.m and i.v. (CON), and imidocarb 2.4 mg/kg bwt i.m. with one of 3 treatments i.v.: 0.9% saline (IMI), atropine 0.02 mg/kg bwt (IMATROP) and glycopyrrolate 0.0025 mg/kg bwt (IMGLYCO). Clinical data, gastrointestinal motility via borborygmi and frequency of contractions in the duodenum, caecum and right dorsal colon assessed with transabdominal ultrasound, and faecal data were measured. RESULTS: After imidocarb/saline treatment colic and diarrhoea were noted in 3 and 4 horses, respectively, faecal production and defaecation were increased for 3 h and faecal water percentage for 6 h. Colic was noted after atropine treatment in 4 horses, borborygmi and frequency of right dorsal colon contractions were significantly decreased for 2 h 15 min, and faecal production was not significantly different from CON. After glycopyrrolate treatment, colic was seen in one horse, frequency of intestinal contractions and faecal data were not significantly different from CON, and borborygmi was significantly decreased from CON at 1 h 15 min. CONCLUSIONS: Results of this study suggest that glycopyrrolate is superior to atropine in ameliorating the adverse effects of imidocarb. POTENTIAL RELEVANCE: Glycopyrrolate could be administered with imidocarb in horses with piroplasmosis to reduce the adverse effects of imidocarb.

22q13.3 deletion syndrome: clinical and molecular analysis using array CGH.

The 22q13.3 deletion syndrome results from loss of terminal segments of varying sizes at 22qter. Few genotype-phenotype correlations have been found but all patients have mental retardation and severe delay, or absence of, expressive speech. We carried out clinical and molecular characterization of 13 patients. Developmental delay and speech abnormalities were common to all and comparable in frequency and severity to previously reported cases. Array-based comparative genomic hybridization showed the deletions to vary from 95 kb to 8.5 Mb. We also carried out high-resolution 244K array comparative genomic hybridization in 10 of 13 patients, that defined the proximal and distal breakpoints of each deletion and helped determine the size, extent, and gene content within the deletion. Two patients had a smaller 95 kb terminal deletion with breakpoints within the SHANK3 gene while three other patients had a similar 5.5 Mb deletion implying the recurrent nature of these deletions. The two largest deletions were found in patients with ring chromosome 22. No correlation could be made with deletion size and phenotype although complete/partial SHANK3 was deleted in all patients. There are very few reports on array comparative genomic hybridization analysis on patients with the 22q13.3 deletion syndrome, and we aim to accurately characterize these patients both clinically and at the molecular level, to pave the way for further genotype-phenotype correlations. (c) 2010 Wiley-Liss, Inc.

[Headache after coughing: consider cough headache]. / Hoofdpijn na hoesten: denk aan hoesthoofdpijn.

A 67-year-old male and a 43-year-old female were referred to hospital with headaches after intracranial pressure increasing activities, such as coughing. Both patients were diagnosed with primary cough headache. In the case of the first patient, this diagnosis was considered shortly after presentation. His headache disappeared with the standard treatment for primary cough headache, consisting of indomethacin and a proton pump inhibitor. The second patient received medicinal and surgical treatment for rhinosinusitis. These treatments did not improve the headache symptoms. Eventually she was also diagnosed with primary cough headache, and became pain-free with indomethacin and a proton pump inhibitor. Primary cough headache should be differentiated from secondary cough headache, in which the symptoms are caused by structural abnormalities of the brain. Additional investigation is required to differentiate between the two. The diagnosis of primary cough headache is supported by a positive reaction to trial treatment with indomethacin.

Why ischemic stroke patients do not receive thrombolytic treatment: results from a general hospital.

OBJECTIVES: To determine the proportion of patients with an ischemic stroke that received intravenous (IV) thrombolytic treatment, and reasons why patients are not treated. METHODS: A prospective registry of all patients with an ischemic stroke admitted to our emergency department (ED). RESULTS: A total of 286 patients with an ischemic stroke were admitted. Eighty-one patients were admitted within 3 h of onset of neurological deficit, of which 28 received IV thrombolysis. In 25 patients no thrombolytic treatment was given because of the presence of the National Institute of Neurological Disorders and Stroke (NINDS) exclusion criteria, and one patient refused treatment. No thrombolytic treatment was given to 27 patients because of mild neurological deficit or rapid clinical improvement, and after 3 months all these patients were independently living at home without nursing help. Despite a public campaign to gain awareness concerning stroke, the majority of the patients arrived too late at the ED for thrombolytic treatment. CONCLUSIONS: A large proportion of the patients with an ischemic stroke are admitted too late to receive IV thrombolysis. More needs to be done to increase both public and medical awareness of stroke as a treatable emergency.

Does the pre-ischaemic administration of sevoflurane reduce myocardial stunning? A porcine experimental model.

BACKGROUND: In a porcine model, the cardioprotective effect of sevoflurane was studied with regard to the preservation of myocardial contractility (myocardial stunning) after a myocardial ischaemic insult. METHODS: Twenty-seven pigs were randomized to receive either a dual 4% sevoflurane inhalation period as a supplement to pentobarbital anaesthesia or pentobarbital anaesthesia only before a 15-min ischaemic insult on the left anterior descending coronary artery. The ischaemic period was followed by 180 min of reperfusion. Myocardial contractility was assessed by myocardial sonomicrometry. RESULTS: A significant difference was found between the sevoflurane group and the control group at 5 min of reperfusion. However, subsequently, there was no overall difference between the two groups. CONCLUSION: Sevoflurane administered as a pre-ischaemic bolus does not provide long-term improvement of the myocardial contractility. However, it can be speculated that sevoflurane may induce an early improvement in contractility.

Evaluation of a novel method for measuring tissue blood flow and gases.

In clinical practice a method for assessment of tissue vitality is a sought-after tool. We have developed a new sensor principle, which is able to register changes in tissue concentration of O2 and tissue flow. The technique is based on diffusion of inert gases and mass spectrometer detection of gaseous metabolites. It was hypothesized that the new sensor could register changes in vital parameters after induction and release of an ischaemic insult to muscular tissue. The sensor performance was evaluated in ten anaesthetized pigs subjected to local muscular ischaemia. Preliminary data from this study indicate the validity of registered hypoxia and reduction in tissue flow as a consequence of compromised blood supply. It was concluded that although precise calibration of the technique is not yet established, it holds promise as a technique that can be used to monitor changes in tissue vitality.

Genome-wide linkage in a large Dutch consanguineous family maps a locus for intracranial aneurysms to chromosome 2p13.

BACKGROUND AND PURPOSE: Familial occurrence of intracranial aneurysms suggests a genetic factor in the development of these aneurysms. In this study, we present the identification of a susceptibility locus for the development of intracranial aneurysms detected by a genome-wide linkage approach in a large consanguineous pedigree. METHODS: Patients with clinical signs and symptoms of intracranial aneurysms, confirmed by radiological, surgical, or postmortem investigations, were included in the study. Magnetic resonance angiography was used to detect asymptomatic aneurysms in relatives. RESULTS: Seven out of 20 siblings had an intracranial aneurysm. Genome-wide multipoint linkage analysis showed a significant logarithm of the odds score of 3.55. CONCLUSIONS: In a large consanguineous pedigree intracranial aneurysms are linked to chromosome 2p13 in a region between markers D2S2206 and D2S2977.

Anticipation in familial intracranial aneurysms in consecutive generations.

Intracranial aneurysms (IA) are the major cause of subarachnoid haemorrhages (SAH). A positive family history for SAH is reported in 5-10% of the patients. The mode of inheritance is not unambiguously established; both autosomal dominant and recessive modes have been reported. In sporadic as well as in familial SAH, approximately 60% of the SAH patients are female. Recently, anticipation has been described in familial SAH. Since up to 15% of the SAHs are not caused by an IA, we have analysed anticipation, sex ratio and mode of inheritance only in families with patients with a proven IA in two consecutive generations. A total of 10 families were studied in which at least two persons in consecutive generations were affected by SAH, a symptomatic IA (SIA) or a presymptomatic IA (PIA). We also analysed published data from families with a proven IA in two consecutive generations on age of SIA onset and sex ratios among affected family members (both SIA and PIA). The age of SIA onset in the parental generation (mean 55.5 years) differed significantly from the age of onset in their children (mean 32.4 years). In the parental generation 11 men and 37 women were affected (both SIA and PIA), in the consecutive generation these numbers were 28 men and 32 women. There is a significant difference in sex ratio of affected family members when the generations are compared (P<0.02). No family could be found in which three consecutive generations were affected by an IA (SIA or PIA).

Subdural hygroma: a rare complication of spinal anesthesia.

IMPLICATIONS: We describe a patient with frontal hygroma after spinal anesthesia--a rare complication. This condition should be considered in patients after spinal anesthesia with persisting orthostatic headache. Risk factors include ventriculo-peritoneal shunt or brain atrophy caused by old age.

Myosin-I nomenclature.

We suggest that the vertebrate myosin-I field adopt a common nomenclature system based on the names adopted by the Human Genome Organization (HUGO). At present, the myosin-I nomenclature is very confusing; not only are several systems in use, but several different genes have been given the same name. Despite their faults, we believe that the names adopted by the HUGO nomenclature group for genome annotation are the best compromise, and we recommend universal adoption.

Dynamic forces in the cell cycle affecting fibroblasts in pressure ulcers.

Utilizing specific cell cycle markers of gene activity, temporal changes in the equilibrium of proliferating and non proliferating fibroblasts were shown in pressure ulcers after 36 days of quality care. Average cell counts from multiple tissue sections showed that fibroblast nuclei were stained in decreasing order by antibodies to p21, p21/proliferating cell nuclear antigen (PCNA) and PCNA. P21 labeling suggested that the majority of ulcer fibroblasts were senescent. Fibroblast nuclei showing PCNA staining identified those fibroblasts that were capable of synthesizing DNA and contributing to pressure ulcer repair. Increased rates of wound closure were correlated with a decreasing number of p21 positive cells and an increasing portion of PCNA labeled cells. While the proportion of antigens appeared to correlate with the status of wound closure after 36 days of quality care, they did not always appear to reflect the final outcome of the pressure ulcer. No significant differences were observed in ulcer fibroblasts labeled with p21 at 0 and 10 days, however, the differences were significant after 36 days of quality care (p = 0.05, analysis of variance, post hoc Tukey test). The cellular contribution to pressure ulcer repair appeared to occur from ulcer fibroblasts that were capable of division, of emerging from quiescence, and that were successful in repairing their DNA.

A millennial myosin census.

The past decade has seen a remarkable explosion in our knowledge of the size and diversity of the myosin superfamily. Since these actin-based motors are candidates to provide the molecular basis for many cellular movements, it is essential that motility researchers be aware of the complete set of myosins in a given organism. The availability of cDNA and/or draft genomic sequences from humans, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Dictyostelium discoideum has allowed us to tentatively define and compare the sets of myosin genes in these organisms. This analysis has also led to the identification of several putative myosin genes that may be of general interest. In humans, for example, we find a total of 40 known or predicted myosin genes including two new myosins-I, three new class II (conventional) myosins, a second member of the class III/ninaC myosins, a gene similar to the class XV deafness myosin, and a novel myosin sharing at most 33% identity with other members of the superfamily. These myosins are in addition to the recently discovered class XVI myosin with N-terminal ankyrin repeats and two human genes with similarity to the class XVIII PDZ-myosin from mouse. We briefly describe these newly recognized myosins and extend our previous phylogenetic analysis of the myosin superfamily to include a comparison of the complete or nearly complete inventories of myosin genes from several experimentally important organisms.

[Coronary bypass surgery without heart-lung-machine. First experiences and results after two years]. / Koronar bypasskirurgi uden hjerte-lunge-maskine. Første erfaringer og resultater efter to år.

Results and experiences two years after the introduction of off-pump coronary artery bypass (OPCAB) are presented. The material includes 95 patients, where 24 patients had a high preoperative risk due to unstable angina, concomitant diseases or relative contraindications to conventional bypass surgery. Per- and postoperative course was characterized by low morbidity with ultra fast track recovery, no detectable levels of coronary enzyme release in the majority of patients, no reoperations for bleeding and early discharge from the hospital. There were two in-hospital deaths, both patients from the high risk group, where one patient died due to a preoperative myocardial infarction, while the other death was not related to cardiac disease. Follow-up results were fully satisfactory, where 86% of the patients were free from anginal symptoms three months after surgery. As a consequence of these positive experiences, OPCAB surgery is offered to an increasing number of patients, currently 25% of our CABG procedures.

Type III collagen deficiency in a family with intracranial aneurysms.

We present a family with 2 female cousins with intracranial aneurysms and type III collagen deficiency. DNA analysis revealed no mutations in the COL3A1 gene, encoding type III collagen, and including the segment encoding the C-propeptide of type III collagen. The 2 patients with low type III collagen production and intracranial aneurysms had inherited different type III collagen alleles. The type III collagen deficiency in this family may results from defects during posttranslational modification or from an altered collagen metabolism.

In vitro fibroblast populated collagen lattices are not good models of in vivo clinical wound healing.

In chronic wounds, the healing process is prolonged and incomplete, proceeding in an uncoordinated manner, and resulting in poor anatomical and functional outcome. There have been numerous attempts to discover models that mimic human wound healing processes. The fibroblast populated collagen lattice is one such model that has been proposed. This study evaluated whether the fibroblast populated collagen lattice can be a model of chronic wound healing using the pressure ulcer as a paradigm. Fibroblast cultures of wound biopsies and wound volume measurements were obtained serially during a four arm blinded, placebo-controlled sequential cytokine clinical trial of pressure ulcers. Fibroblasts obtained from study patients were added to collagen lattices and contraction was determined daily for 10 days. Collagen gel-area measurements were converted to reflect percentage of gel contraction. These data of both edge and base wound biopsies on days 0, 10, and 36 were categorized into treatment groups and one-way analysis of variance showed no significant differences in contraction among these groups. When considering all fibroblast populated collagen lattices, there was significantly greater contraction at days 10 and 36 for cells from both edge and base biopsies compared to day 0 (p < 0.05). The Spearman Rank Correlation test comparing all patients with fibroblast populated collagen lattice results from fibroblasts obtained at the edge or base of the wound at days 0, 10, and 36 and clinical pressure ulcer healing on day 36 showed no correlation. This lack of correlation not only persisted for each of the four treatment arms but also for responder status based on decrease in wound volume over the 35 day trial period. In conclusion, chronic wound healing is a complex process that is not modeled by in vitro fibroblast populated collagen lattices.

Myosin-X, a novel myosin with pleckstrin homology domains, associates with regions of dynamic actin.

Myosin-X is the founding member of a novel class of unconventional myosins characterized by a tail domain containing multiple pleckstrin homology domains. We report here the full-length cDNA sequences of human and bovine myosin-X as well as the first characterization of this protein's distribution and biochemical properties. The 235 kDa myosin-X contains a head domain with <45% protein sequence identity to other myosins, three IQ motifs, and a predicted stalk of coiled coil. Like several other unconventional myosins and a plant kinesin, myosin-X contains both a myosin tail homology 4 (MyTH4) domain and a FERM (band 4.1/ezrin/radixin/moesin) domain. The unique tail domain also includes three pleckstrin homology domains, which have been implicated in phosphatidylinositol phospholipid signaling, and three PEST sites, which may allow cleavage of the myosin tail. Most intriguingly, myosin-X in cultured cells is present at the edges of lamellipodia, membrane ruffles, and the tips of filopodial actin bundles. The tail domain structure, biochemical features, and localization of myosin-X suggest that this novel unconventional myosin plays a role in regions of dynamic actin.