Acceleration of electrons in the plasma wakefield of a proton bunch.

High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1-5, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6-9 or electron bunch10,11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14-16, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17-19 uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20 means that our results are an important step towards the development of future high-energy particle accelerators21,22.

Proton-driven plasma wakefield acceleration in AWAKE.

In this article, we briefly summarize the experiments performed during the first run of the Advanced Wakefield Experiment, AWAKE, at CERN (European Organization for Nuclear Research). The final goal of AWAKE Run 1 (2013-2018) was to demonstrate that 10-20 MeV electrons can be accelerated to GeV energies in a plasma wakefield driven by a highly relativistic self-modulated proton bunch. We describe the experiment, outline the measurement concept and present first results. Last, we outline our plans for the future. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Anisotropic leaky-mode modulator for holographic video displays.

Every holographic video display is built on a spatial light modulator, which directs light by diffraction to form points in three-dimensional space. The modulators currently used for holographic video displays are challenging to use for several reasons: they have relatively low bandwidth, high cost, low diffraction angle, poor scalability, and the presence of quantization noise, unwanted diffractive orders and zero-order light. Here we present modulators for holographic video displays based on anisotropic leaky-mode couplers, which have the potential to address all of these challenges. These modulators can be fabricated simply, monolithically and at low cost. Additionally, these modulators are capable of new functionalities, such as wavelength division multiplexing for colour display. We demonstrate three enabling properties of particular interest-polarization rotation, enlarged angular diffraction, and frequency domain colour filtering-and suggest that this technology can be used as a platform for low-cost, high-performance holographic video displays.

Incidence of thrombosis in perioperative and non-operative myocardial infarction.

BACKGROUND: The contribution of thrombosis to the aetiology of perioperative myocardial infarction (MI) is uncertain. We used optical coherence tomography (OCT) to determine the presence of thrombus and plaque morphology in patients experiencing a perioperative MI and matched patients experiencing a non-operative MI using OCT. METHODS: We conducted a single-centre, prospective, cohort study. Thirty patients experiencing a perioperative MI and 30 matched patients experiencing a non-operative MI, without ST elevation, underwent OCT to determine the presence of thrombus and culprit lesion plaque morphology. Angiography and OCT were performed a mean of 1.93(1.09) days and 1.53(0.68) days after the onset of perioperative and non-operative MI, respectively. OCT images were evaluated by an independent core laboratory without knowledge of whether the patient had suffered a perioperative or non-operative MI. RESULTS: We identified thrombus at the culprit lesion in four of 30 patients (13.3%) who experienced a perioperative MI and in 20 of 30 patients (66.7%) who experienced a non-operative MI, P<0.01. The only non-culprit lesion with thrombus was in a perioperative MI patient who also had a culprit lesion thrombus. Perioperative and non-operative MI culprit lesions demonstrated fibroatheroma in 18 patients (60.0%) us 20 patients (66.7%), respectively (P=0.52) and thin cap fibroatheroma in one patient (3.3%) us five patients (16.7%), respectively (P=0.11). One perioperative MI patient (3.3%) suffered a cardiac death and no non-operative MI patient died during the 30-day follow-up. CONCLUSIONS: Thrombosis was less common in perioperative than non-operative MI, despite similar underlying plaque morphology.

Serum uric acid does not predict incident metabolic syndrome in a population with high prevalence of obesity.

AIM: To evaluate whether uric acid (UA) predicts 4-yr incidence of metabolic syndrome (MetS) in non-diabetic participants of the Strong Heart Study (SHS) cohort. METHODS AND RESULTS: In this population-based prospective study we analyzed 1499 American Indians (890 women), without diabetes or MetS, controlled during the 4th SHS exam and re-examined 4 years later during the 5th SHS exam. Participants were divided into sex-specific tertiles of UA and the first two tertiles (group N) were compared with the third tertile (group H). Body mass index (BMI = 28.3 ± 7 vs. 31.1 ± 7 kg/m(2)), fat-free mass (FFM = 52.0 ± 14 vs. 54.9 ± 11 kg), waist-to-hip ratio, HOMA-IR (3.66 vs. 4.26), BP and indices of inflammation were significantly higher in group H than in group N (all p < 0.001). Incident MetS at the time of the 5th exam was more frequent in group H than group N (35 vs. 28%, OR 1.44 (95% CI = 1.10-1.91; p < 0.01). This association was still significant (OR = 1.13, p = 0.04) independently of family relatedness, sex, history of hypertension, HOMA-IR, central adiposity and renal function, but disappeared when fat-free mass was included in the model. CONCLUSIONS: In the SHS, UA levels are associated to parameters of insulin resistance and to indices of inflammation. UA levels, however, do not predict incident MetS independently of the initial obesity-related increased FFM.

Differences in morphology of temporomandibular joint ankylosis of traumatic and infective origin.

The aim of this study was to determine whether there are any differences in morphology between temporomandibular joint ankylosis (TMJA) of traumatic and infective origin. Cone beam computed tomography (CBCT) scans of 25 patients (28 joints) with TMJA of traumatic origin (trauma group) and 15 patients (15 joints) with TMJA of infectious origin (infection group) were included. The following morphological parameters were evaluated on multiple sections of the CBCT scans: lateral juxta-articular bone growth, residual condyle, residual glenoid fossa, ramus thickening, ankylotic mass fusion line, sclerosis of the ankylosed condyle and spongiosa of the glenoid fossa, and mastoid and glenoid fossa air cell obliteration. Lateral juxta-articular bone growth, juxta-articular extension of fusion, and the presence of normal medial residual condyle and residual glenoid fossa were exclusively found in post-traumatic TMJA. There were differences in ramus thickening (82.1% in trauma vs 53.3% in infection), sclerosis of the ankylosed condyle (100% in trauma vs 60% in infection), and sclerosis of the spongiosa of the glenoid fossa (100% in trauma vs 46.7% in infection) between the trauma and infection groups. Mastoid and glenoid fossa air cell obliteration was found more frequently in the infection group (mastoid obliteration: 23.1% in infection vs 4% in trauma; glenoid obliteration: 66.7% in infection vs 55.6% in trauma ). CBCT imaging can be helpful in differentiating between TMJA of traumatic and infectious origin.

Primary bilateral pontine demyelination in a cat with similarity to central pontine myelinolysis.

An adult cat was presented with the history of 3 months' weight loss and more recent loss of balance and ataxia. An abdominal mass was palpable; results of neurologic examination suggested a brainstem disorder. The owners elected euthanasia. Postmortem findings included suppurative jejunal lymphadenitis and bilateral demyelination in the ventral pons with sparing of axons and neuronal soma. The location and character of the lesion mimicked those of human central pontine myelinolysis, an iatrogenic condition that may follow rapid correction of hyponatremia or develop spontaneously in patients with malnutrition or energy deprivation. In this cat, the poor nutritional state may have contributed to the development of this novel pontine lesion.

Nutritional intervention during maxillomandibular fixation of jaw fractures prevents weight loss and improves quality of life.

Maxillomandibular fixation (MMF) for the management of jaw fractures leads to compromised nutritional intake and consequent weight loss and poor quality of life (QoL). The present study aimed to evaluate the effectiveness of a home-based dietary plan to prevent weight loss, and its effect on the QoL of patients who underwent four weeks of MMF for the treatment of maxillofacial fractures. A total of 50 patients were randomised into nutritional intervention (Group1) and non-intervention groups (Group 2). Patients in Group1 were counselled by a dietitian and given a diet plan. Patients in Group 2 were advised to take a liquid diet of their own choice in the form of shakes, juices, and milk, along with protein supplements. Patients in Group1 lost significantly less weight than those in Group 2 (p=0.001) at week four of follow up. Group1 patients had significantly better oral health-related QoL in the 'physical pain' domain during the two weeks of MMF, and in the 'physical discomfort' and 'psychological disability' domains two weeks after the release of MMF. They had significantly better nutrition-related QoL in all the domains during the two weeks of MMF and, except for the 'physical' domain, also during the two weeks after its release. Individual home-based diet plans effectively helped the patients maintain their weight and improved QoL.

Experimental exploration of a mixed helium/carbon beam for online treatment monitoring in carbon ion beam therapy.

Recently, it has been proposed that a mixed helium/carbon beam could be used for online monitoring in carbon ion beam therapy. Fully stripped, the two ion species exhibit approximately the same mass/charge ratio and hence could potentially be accelerated simultaneously in a synchrotron to the same energy per nucleon. At the same energy per nucleon, helium ions have about three times the range of carbon ions, which could allow for simultaneous use of the carbon ion beam for treatment and the helium ion beam for imaging. In this work, measurements and simulations of PMMA phantoms as well as anthropomorphic phantoms irradiated sequentially with a helium ion and a carbon ion beam at equal energy per nucleon are presented. The range of the primary helium ion beam and the fragment tail of the carbon ion beam exiting the phantoms were detected using a novel range telescope made of thin plastic scintillator sheets read out by a flat-panel CMOS sensor. A 10:1 carbon to helium mixing ratio is used, generating a helium signal well above the carbon fragment background while adding little to the dose delivered to the patient. The range modulation of a narrow air gap of 1 mm thickness in the PMMA phantom that affects less than a quarter of the particles in a pencil beam were detected, demonstrating the achievable relative sensitivity of the presented method. Using two anthropomorphic pelvis phantoms it is shown that small rotations of the phantom as well as simulated bowel gas movements cause detectable changes in the helium/carbon beam exiting the phantom. The future prospects and limitations of the helium/carbon mixing as well as its technical feasibility are discussed.

Understanding extraction and beam transport in the ISIS H(-) Penning surface plasma ion source.

The ISIS H(-) Penning surface plasma source has been developed to produce beam currents up to 70 mA and pulse lengths up to 1.5 ms at 50 Hz. This paper details the investigation into beam extraction and beam transport in an attempt to understand the beam emittance and to try to improve the emittance. A scintillator profile measurement technique has been developed to assess the performance of different plasma electrode apertures, extraction electrode geometries, and postextraction acceleration configurations. This work shows that the present extraction, beam transport, and postacceleration system are suboptimal and further work is required to improve it.

A comparative assessment of intranasal and oral dexmedetomidine for procedural sedation in pediatric dental patients.

OBJECTIVES: The objective of this study was to assess the safety and efficacy of intranasal and oral dexmedetomidine for procedural sedation in pediatric dental patients. MATERIALS AND METHODS: Forty-four uncooperative American Society of Anesthesiologists Grade-I children, requiring dental treatment were randomly divided into four groups who received different doses of dexmedetomidine through intranasal and oral routes. The vital signs were monitored continuously during each visit. RESULTS: In this study, significant (P < 0.05) differences were found in the onset of sedation, duration, and recovery time between intranasal and oral groups. All vital signs were within normal physiological limits with no significant adverse effects in either of the groups. CONCLUSION: Dexmedetomidine is a safe and effective agent for procedural sedation in pediatric dental patients with intranasal route having distinct advantages over oral route.

Impact of zinc supplementation on subsequent morbidity and growth in Bangladeshi children with persistent diarrhoea.

This study was conducted to explore whether supplementation of zinc to children during persistent diarrhoea has any subsequent effect on morbidity and growth. A prospective follow-up study was conducted among children, aged 3-24 months, with persistent diarrhoea, who participated earlier in a double-blind randomized placebo-controlled trial. During persistent diarrhoea, children were randomly allocated to receive either zinc in multivitamin syrup or only multivitamin syrup for two weeks. After recovering from diarrhoea, 76 children in the multi-vitamin syrup and 78 children in the zinc plus multivitamin syrup group were followed up for subsequent morbidity and growth. Weekly morbidity and two-weekly anthropometric data were collected for the subsequent 12 weeks. Data showed that episodes and duration of diarrhoea were reduced by 38% and 44% respectively with supplementation of zinc. There was no significant difference in the incidence or duration of respiratory tract infection between the zinc-supplemented and the non-supplemented group. Improved linear growth was observed in underweight children (weight-for-age <70% of the National Center for Health Statistics standard) who received zinc compared to those who did not receive.

Impact of zinc deficiency on vibrio cholerae enterotoxin-stimulated water and electrolyte transport in animal model.

The effect of zinc deficiency on the function of the intestine to absorb water and electrolytes was studied in animal models, stimulated by Vibrio cholerae enterotoxin. Sprague-Dawley rats, used in the study, were divided into four groups: Zinc-deficient, ad libitum zinc-fed control, zinc weight-matched control, and zinc-deficient acutely-repleted. 14C-labelled polyethylene glycol solution was used for measuring the absorption capacity of the small intestine. Significantly lower absorption of water and sodium per cm of the intestine was observed in the zinc-deficient animals compared to the ad libitum zinc-fed control animals (p < 0.01). An improved absorption capacity was equally observed in the zinc-deficient acutely-repleted animals and ad libitum zinc-fed control group. The zinc-deficient animals showed four times greater cholera toxin-induced net secretions of water and sodium compared to the ad libitum zinc-fed group (p < 0.01), while a 40% reduction was observed in the zinc-deficient acutely-repleted group. The results suggest that zinc deficiency is associated with reduced absorption of water and electrolytes and increased secretion of the same stimulated by cholera toxin.

The impact of implantable cardiac defibrillators for primary prophylaxis in the community: baseline risk and clinically meaningful benefits.

OBJECTIVE: To estimate the baseline risk of arrhythmic death required for prophylactic implantable cardiac defibrillators (ICDs) to result in clinically meaningful survival benefits in the population. BACKGROUND: While proven efficacious, the absolute survival impact of ICDs for the primary prevention of sudden cardiac death among patients with left ventricular (LV) dysfunction is highly dependent upon patient's baseline risk of arrhythmic death. METHODS: Using echocardiographic data from a random sample of patients identified from community echocardiographic laboratories, patients with moderate or severe LV dysfunction (ejection fraction < 35%) were linked to administrative databases to characterize baseline mortality risk (median follow-up duration of 4.85 years). Relative efficacy was ascertained from meta-analysis and clinical trial data. The baseline annual risk of arrhythmic death required for prophylactic ICDs to result in clinically meaningful survival benefits in the population was estimated at different ranges of relative efficacy and numbers needed to treat (NNTs) thresholds. RESULTS: LV dysfunction was a significant independent predictor of adverse outcomes. In total, 35.4% of the patients with moderate to severe LV dysfunction died during the follow-up period. Assuming a base-case relative efficacy of 66%, we estimated that the baseline risk for arrhythmic death required to exert a clinically meaningful NNT threshold of 50 in order to prevent one death (from any cause) was 3% per year or higher. CONCLUSIONS: The survival impact and cost-effectiveness of prophylactic ICDs in the population will depend upon the ability to risk-stratify and identify patients whose baseline risk for sudden cardiac death exceed 3% per year.

Risk factors and effect of selective removal on retroviral infections prevalence in Belgian stray cats.

The aim of this study was to evaluate the effect of several risk/protective factors and predictors on the prevalence of feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) infections in 302 stray cats captured during a trap-neuter-release programme in a mixed urban-rural area from Belgium, from 2010 to 2012. The impact of selective removal of FIV-positive cats on the apparent prevalence in the remaining population over this three-year period was also assessed. The seroprevalences over three years were 18.8 per cent for FIV and 0.7 per cent for FeLV. For FIV, the seroprevalence decreased significantly from the first year of the programme (2010; 30.5 per cent) to the last (2012; 13.1 per cent). Sex (male) and age (adult and old cats) were risk factors, while the year of sampling (years 2011 and 2012) was a protective factor. Age, sex and location were the most relevant predictors of FIV status. The data presented in this study revealed a very high FIV seroprevalence in Belgian stray cats, while FeLV was almost absent. The selective removal of positive cats had a drastic effect on the FIV seroprevalence in the remaining cat population.

Neuropathologic findings in a case of OFDS type VI (Váradi syndrome).

Oral-facial-digital syndrome type VI (OFDS VI) or Váradi syndrome is a rare autosomal-recessive disorder distinguished from other oral-facial-digital syndromes by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities. Histopathologic characterization of the cerebellar abnormalities has not been described previously. We describe the neuropathologic findings in a stillborn, 21-week estimated gestational age (EGA) male fetus diagnosed antenatally with signs of OFDS VI. Autopsy findings included: facial abnormalities, postaxial central polydactyly of the right hand, bilateral bifid toes, and absence of cerebellar vermis with hypoplasia of the hemispheric cortex. Microscopic analysis of the cerebellum demonstrated absence of the subpial granular cell layer and disruption or dysgenesis of the glial architecture. These histopathologic findings suggest that a primary neuronal or glial cell defect, rather than an associated Dandy-Walker malformation, may account for the cerebellar abnormalities in this form of oral-facial-digital syndrome.

Preinfusion anxiety and laboratory-induced panic attacks in panic disorder patients.

Seventy panic disorder patients participated in a double-blind, placebo-controlled, randomized infusion study in which sodium lactate and isoproterenol were used to induce panic anxiety. Patients who panicked during lactate, isoproterenol, and placebo infusions generally had higher preinfusion anxiety scores. These findings held true irrespective of the order the infusions were given. Stepwise multiple regression analyses comparing panickers with nonpanickers as the criterion variable revealed that the items "afraid of going crazy," "feeling unsteady," and "feeling paralyzed" on the Panic Description Scale had the highest predicting values.

Competitive flow from a fully patent coronary artery does not limit acute mammary graft flow.

The shriveled, stenotic mammary graft sometimes observed after internal mammary artery (IMA) to coronary artery bypass grafting has been attributed to competitive flow from the insufficiently stenosed native coronary vessel. To study further the effects of native coronary artery competing flow on IMA graft flow, 10 dogs (mean weight, 23.5 +/- 3.69 kg) underwent coronary artery bypass grafting using the pedicled left IMA anastomosed to a normal, fully patent proximal circumflex (CFX) coronary artery. The procedure was performed through a left thoracotomy, off pump, using a brief local occlusion to perform the anastomosis. Native in situ IMA flow, CFX flow distal to the anastomosis, and IMA graft flow were measured using calibrated electromagnetic flow probes. When the CFX proximal to the anastomosis was occluded transiently, IMA flow increased to supply 100% of the previously measured distal CFX flow (60.2 +/- 7.9 mL/min). When both the IMA graft and CFX proximal to the anastomosis were patent, total distal perfusion was maintained (58.9 +/- 7.8 mL/min) and relative IMA graft flow (26.5 +/- 3.3 mL/min) was proportional to the relative diameter of the IMA graft to the native coronary artery (r = 0.96). The mean flow in the IMA in situ on the chest wall before its division was 23.8 +/- 8.1 mL/min. These results suggest that, at least acutely in a canine model, IMA graft flow is maintained above in situ levels even when grafted to a completely patent coronary artery and that acute competitive flow probably does not cause mammary artery shriveling.

Effect of chronic native flow competition on internal thoracic artery grafts.

Residual competitive flow from the native coronary artery has been proposed as a mechanism that reduces flow in an internal thoracic artery graft (ITA), resulting in narrowing and ultimately failure of the graft. Results from acute experiments have indicated that competitive flow from a fully patent native artery did not abolish ITA graft flow. The present study was designed to examine the consequences of dynamic flow competition between the native vessel and the ITA graft in a chronic model. Fifteen mongrel dogs underwent coronary artery bypass grafting using the pedicled left ITA anastomosed to the normal, fully patent circumflex (CFX) coronary artery. The procedure was performed through a sterile thoracotomy, without systemic cardiopulmonary bypass, using a brief local occlusion to construct the anastomosis. Intraoperatively, ITA flow was measured in situ on the chest wall, before the pedicle was mobilized. Internal thoracic artery graft and distal CFX flow were measured after the anastomosis was completed, with and without brief occlusion of the proximal CFX. Angiography was performed 72 hours, 4 weeks, and 8 weeks later; graft patency and diameter were evaluated. After 8 weeks, open-chest direct flow measurements comparable with the intraoperative assessment were obtained. Two grafts (13%) occluded early, the technical result of poor anastomotic construction. In the 13 remaining animals, all grafts were widely patent at all time points. Internal thoracic artery flow in situ averaged 10.9 +/- 7.8 mL/min (mean +/- standard deviation), and was maintained after grafting (11.5 +/- 4.4 mL/min; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)