Phase Space Dynamics of a Plasma Wakefield Dechirper for Energy Spread Reduction.

Plasma-based accelerators have made impressive progress in recent years. However, the beam energy spread obtained in these accelerators is still at the ∼1% level, nearly one order of magnitude larger than what is needed for challenging applications like coherent light sources or colliders. In plasma accelerators, the beam energy spread is mainly dominated by its energy chirp (longitudinally correlated energy spread). Here we demonstrate that when an initially chirped electron beam from a linac with a proper current profile is sent through a low-density plasma structure, the self-wake of the beam can significantly reduce its energy chirp and the overall energy spread. The resolution-limited energy spectrum measurements show at least a threefold reduction of the beam energy spread from 1.28% to 0.41% FWHM with a dechirping strength of ∼1 (MV/m)/(mm pC). Refined time-resolved phase space measurements, combined with high-fidelity three-dimensional particle-in-cell simulations, further indicate the real energy spread after the dechirper is only about 0.13% (FWHM), a factor of 10 reduction of the initial energy spread.

Comparison of high-sensitivity cardiac troponin I and T for the prediction of cardiac complications after non-cardiac surgery.

BACKGROUND: We aimed to directly compare preoperative high-sensitivity cardiac troponin (hs-cTn) I and T concentration for the prediction of major cardiac complications after non-cardiac surgery. METHODS: We measured hs-cTnI and hs-cTnT preoperatively in a blinded fashion in 1022 patients undergoing non-cardiac surgery. The primary endpoint was a composite of major cardiac complications including cardiac death, cardiac arrest, myocardial infarction, clinically relevant arrhythmias, and acute heart failure within 30 days. We hypothesized that the type of surgery may impact on the predictive accuracy of hs-cTnI/T and stratified all analyses according to the type of surgery. RESULTS: Major cardiac complications occurred in 108 (11%) patients, 58/243 (24%) patients undergoing vascular surgery and 50/779 (6%, P < .001) patients undergoing non-vascular surgery. Using regulatory-approved 99th percentile cut-off concentrations, preoperative hs-cTnI elevations were less than one-fifth as common as preoperative hs-cTnT elevations (P < .001). Among patients undergoing vascular surgery, preoperative hs-cTnI concentrations, but not hs-cTnT, was an independent predictor of cardiac complications (adjusted odds ratio (aOR) 1.5, 95% confidence interval (95% CI) 1.0-2.1). The area under the receiver-operating characteristics curve (AUC) was 0.67 (95% CI, 0.59-0.75) for hs-cTnI versus 0.59 (95% CI 0.51-0.67, P = .012) for hs-cTnT. In contrast, among patients undergoing non-vascular surgery both preoperative hs-cTnI and hs-cTnT were independent predictors of the primary endpoint (aOR 1.6, 95% CI 1.3-2.0, and aOR 3.0, 95% CI 2.0-4.6, respectively) and showed higher predictive accuracy (AUC 0.77, 95% CI, 0.71-0.83, and 0.79, 95% CI 0.73-0.85, P = ns). CONCLUSIONS: Preoperative hs-cTnI and hs-cTnT concentrations predict major cardiac complications after non-vascular surgery, while, in patients undergoing vascular surgery, hs-cTnI may have better accuracy.

Prediction of major cardiac events after vascular surgery.

OBJECTIVE: Predicting cardiac events is essential to provide patients with the best medical care and to assess the risk-benefit ratio of surgical procedures. The aim of our study was to evaluate the performance of the Revised Cardiac Risk Index (Lee) and the Vascular Study Group of New England Cardiac Risk Index (VSG) scores for the prediction of major cardiac events in unselected patients undergoing arterial surgery and to determine whether the inclusion of additional risk factors improved their accuracy. METHODS: The study prospectively enrolled 954 consecutive patients undergoing arterial vascular surgery, and the Lee and VSG scores were calculated. Receiver operating characteristic curves for each cardiac risk score were constructed and the areas under the curve (AUCs) compared. Two logistic regression models were done to determine new variables related to the occurrence of major cardiac events (myocardial infarction, heart failure, arrhythmias, and cardiac arrest). RESULTS: Cardiac events occurred in 120 (12.6%) patients. Both scores underestimated the rate of cardiac events across all risk strata. The VSG score had AUC of 0.63 (95% confidence interval [CI], 0.58-0.68), which was higher than the AUC of the Lee score (0.58; 95% CI, 0.52-0.63; P = .03). Addition of preoperative anemia significantly improved the accuracy of the Lee score to an AUC of 0.61 (95% CI, 0.58-0.67; P = .002) but not that of the VSG score. CONCLUSIONS: The Lee and VSG scores have low accuracy and underestimate the risk of major perioperative cardiac events in unselected patients undergoing vascular surgery. The Lee score's accuracy can be increased by adding preoperative anemia. Underestimation of major cardiac complications may lead to incorrect risk-benefit assessments regarding the planned operation.

Femtosecond Probing of Plasma Wakefields and Observation of the Plasma Wake Reversal Using a Relativistic Electron Bunch.

We show that a high-energy electron bunch can be used to capture the instantaneous longitudinal and transverse field structures of the highly transient, microscopic, laser-excited relativistic wake with femtosecond resolution. The spatiotemporal evolution of wakefields in a plasma density up ramp is measured and the reversal of the plasma wake, where the wake wavelength at a particular point in space increases until the wake disappears completely only to reappear at a later time but propagating in the opposite direction, is observed for the first time by using this new technique.

Cost of Illness in Inflammatory Bowel Disease.

BACKGROUND: Frequent relapses sometimes necessitating hospitalization and the absence of pharmacological cure contribute to substantial healthcare costs in inflammatory bowel diseases (IBDs). The costs of health care in Indian patients with IBD are unknown. AIM: To evaluate the annual costs for treating Crohn's disease and ulcerative colitis. METHODS: A prevalence-based, micro-costing method was used to assess the components of annual costs in a prospective, observational study conducted in a tertiary healthcare center enrolled over a 24-month period beginning of July 2014. RESULTS: At enrollment, 43/59 (72.88%) patients with UC and 18/25 (72%) with CD were in remission. The annual median (IQR) cost per UC and CD patient in remission was INR 43,140 (34,357-51,031) [USD $707 (563-836)] and INR 43,763.5 (32,202-57,372) [USD $717 (527-940)], respectively, and in active disease was INR 52,436.5 (49,229-67,567.75) [$859 (807-1107)] and INR 72,145 (49,447-92,212) [USD $1182 (811-1512)], respectively. Compared with remission, active disease had a 1.4-fold higher cost for CD as compared to UC. In both groups, the greatest component of direct costs was drugs. Thirteen (22%) and 7 (28%) patients with UC and CD needed hospitalization accounting for 23.1 and 20.4% of the total costs, respectively. At one year, direct costs surmounted indirect costs in UC and CD (p < 0.001). Productivity losses contributed to 18.5 and 16% of the overall costs for UC and CD, respectively. CONCLUSION: This first, panoptic, health economic study for IBD from India shows that the costs are driven by medication, productivity losses, and not merely hospitalization alone.

Physical Mechanism of the Transverse Instability in Radiation Pressure Ion Acceleration.

The transverse stability of the target is crucial for obtaining high quality ion beams using the laser radiation pressure acceleration (RPA) mechanism. In this Letter, a theoretical model and supporting two-dimensional (2D) particle-in-cell (PIC) simulations are presented to clarify the physical mechanism of the transverse instability observed in the RPA process. It is shown that the density ripples of the target foil are mainly induced by the coupling between the transverse oscillating electrons and the quasistatic ions, a mechanism similar to the oscillating two stream instability in the inertial confinement fusion research. The predictions of the mode structure and the growth rates from the theory agree well with the results obtained from the PIC simulations in various regimes, indicating the model contains the essence of the underlying physics of the transverse breakup of the target.

Nanoscale Electron Bunching in Laser-Triggered Ionization Injection in Plasma Accelerators.

Ionization injection is attractive as a controllable injection scheme for generating high quality electron beams using plasma-based wakefield acceleration. Because of the phase-dependent tunneling ionization rate and the trapping dynamics within a nonlinear wake, the discrete injection of electrons within the wake is nonlinearly mapped to a discrete final phase space structure of the beam at the location where the electrons are trapped. This phenomenon is theoretically analyzed and examined by three-dimensional particle-in-cell simulations which show that three-dimensional effects limit the wave number of the modulation to between >2k_{0} and about 5k_{0}, where k_{0} is the wave number of the injection laser. Such a nanoscale bunched beam can be diagnosed by and used to generate coherent transition radiation and may find use in generating high-power ultraviolet radiation upon passage through a resonant undulator.

Physics of Phase Space Matching for Staging Plasma and Traditional Accelerator Components Using Longitudinally Tailored Plasma Profiles.

Phase space matching between two plasma-based accelerator (PBA) stages and between a PBA and a traditional accelerator component is a critical issue for emittance preservation. The drastic differences of the transverse focusing strengths as the beam propagates between stages and components may lead to a catastrophic emittance growth even when there is a small energy spread. We propose using the linear focusing forces from nonlinear wakes in longitudinally tailored plasma density profiles to control phase space matching between sections with negligible emittance growth. Several profiles are considered and theoretical analysis and particle-in-cell simulations show how these structures may work in four different scenarios. Good agreement between theory and simulation is obtained, and it is found that the adiabatic approximation misses important physics even for long profiles.

Comparative analysis of copy number variations in ulcerative colitis associated and sporadic colorectal neoplasia.

BACKGROUND: The incidence of and mortality from colorectal cancers (CRC) can be reduced by early detection. Currently there is a lack of established markers to detect early neoplastic changes. We aimed to identify the copy number variations (CNVs) and the associated genes which could be potential markers for the detection of neoplasia in both ulcerative colitis-associated neoplasia (UC-CRN) and sporadic colorectal neoplasia (S-CRN). METHODS: We employed array comparative genome hybridization (aCGH) to identify CNVs in tissue samples of UC nonprogressor, progressor and sporadic CRC. Select genes within these CNV regions as a panel of markers were validated using quantitative real time PCR (qRT-PCR) method along with the microsatellite instability (MSI) in an independent cohort of samples. Immunohistochemistry (IHC) analysis was also performed. RESULTS: Integrated analysis showed 10 overlapping CNV regions between UC-Progressor and S-CRN, with the 8q and 12p regions showing greater overlap. The qRT-PCR based panel of MYC, MYCN, CCND1, CCND2, EGFR and FNDC3A was successful in detecting neoplasia with an overall accuracy of 54% in S-CRN compared to that of 29% in UC neoplastic samples. IHC study showed that p53 and CCND1 were significantly overexpressed with an increasing frequency from pre-neoplastic to neoplastic stages. EGFR and AMACR were expressed only in the neoplastic conditions. CONCLUSION: CNVs that are common and unique to both UC-associated and sporadic colorectal neoplasm could be the key players driving carcinogenesis. Comparative analysis of CNVs provides testable driver aberrations but needs further evaluation in larger cohorts of samples. These markers may help in developing more effective neoplasia-detection strategies during screening and surveillance programs.

Initial clinical experience with ArcCHECK for IMRT/VMAT QA.

Many devices designed for the purpose of performing patient-specific IMRT/VMAT QA are commercially available. In this work we report our experience and initial clinical results with the ArcCHECK. The ArcCHECK consists of a cylindrical array of diode detectors measuring entry and exit doses. The measured result is a cumulative dose displayed as a 2D matrix. The detector array requires both an absolute dose calibration, and a calibration of the detector response, relative to each other. In addition to the calibrations suggested by the manufacturer, various tests were performed in order to assess its stability and performance prior to clinical introduction. Tests of uniformity, linearity, and repetition rate dependence of the detector response were conducted and described in this work. Following initial test-ing, the ArcCHECK device was introduced in the clinic for routine patient-specific IMRT QA. The clinical results from one year of use were collected and analyzed. The gamma pass rates at the 3%/3 mm criterion were reported for 3,116 cases that included both IMRT and VMAT treatment plans delivered on 18 linear accelera-tors. The gamma pass rates were categorized based on the treatment site, treatment technique, type of MLCs, operator, ArcCHECK device, and LINAC model. We recorded the percent of failures at the clinically acceptable threshold of 90%. In addition, we calculated the threshold that encompasses two standard deviations (2 SD) (95%) of QAs (T95) for each category investigated. The commissioning measurements demonstrated that the device performed as expected. The uniformity of the detector response to a constant field arc delivery showed a 1% standard deviation from the mean. The variation in dose with changing repetition rate was within 1 cGy of the mean, while the measured dose showed a linear relation with delivered MUs. Our initial patient QA results showed that, at the clinically selected passing criterion, 4.5% of cases failed. On average T95 was 91%, rang-ing from 73% for gynecological sites to 96.5% for central nervous system sites. There are statistically significant differences in passing rates between IMRT and VMAT, high-definition (HD) and non-HD MLCs, and different LINAC models (p-values << 0.001). An additional investigation into the failing QAs and a com-parison with ion-chamber measurements reveals that the differences observed in the passing rates between the different studied factors can be largely explained by the field size dependence of the device. Based on our initial experience with the ArcCHECK, our passing rates are, on average, consistent with values reported in the AAPM TG-119. However, the significant variations between QAs that were observed based on the size of the treatment fields may need to be corrected to improve the specificity and sensitivity of the device.

Monocyte chemoattractant protein-1, transforming growth factor-beta1, nerve growth factor, resistin and hyaluronic acid as serum markers: comparison between recurrent acute and chronic pancreatitis.

BACKGROUND: Diagnostic parameters that can predict the presence of chronic pancreatitis (CP) in patients with recurrent pain due to pancreatitis would help to direct appropriate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta1 (TGF-beta1), nerve growth factor (NGF), resistin and hyaluronic acid (HA) in patients with recurrent acute pancreatitis (RAP) and CP to assess their ability to differentiate the two conditions. METHODS: Levels of serum markers assessed by enzyme-linked immunosorbent assay (ELISA) were prospectively compared in consecutive patients with RAP, CP and in controls, and stepwise discriminant analysis was performed to identify the markers differentiating RAP from CP. RESULTS: One hundred and thirteen consecutive patients (RAP=32, CP=81) and 78 healthy controls were prospectively enrolled. The mean (SD) age of the patients was 32.0 (14.0) years; 89 (78.8%) were male. All markers were significantly higher in CP patients than in the controls (P<0.001); MCP-1, NGF and HA were significantly higher in RAP patients than in the controls (P<0.001). Stepwise discriminant analysis showed significant difference (P=0.002) between RAP and CP for resistin with an accuracy of 61.9%, discriminant scores of ≤-0.479 and ≥0.189 indicating RAP and CP, respectively. The other markers had no differential value between RAP and CP. CONCLUSION: Serum resistin is a promising marker to differentiate between RAP and CP and needs validation in future studies, especially in those with early CP.

Pancreatic Calculus Causing Biliary Obstruction: Endoscopic Therapy for a Rare Initial Presentation of Chronic Pancreatitis.

INTRODUCTION: Biliary obstruction in chronic calcific pancreatitis (CCP) is often caused by inflammatory or fibrotic strictures of the bile duct, carcinoma of head of pancreas or less commonly by compression from pseudocysts. Pancreatic calculi causing ampullary obstruction and leading to obstructive jaundice is extremely rare. METHODS: The medical records of all patients with CCP or biliary obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP) over 4 years between 2010-2014 at Kasturba Medical College, Manipal were analyzed. RESULTS: Five patients of CCP with impacted pancreatic calculi at the ampulla demonstrated during ERCP were identified. All 5 presented with biliary obstruction and were incidentally detected to have CCP when evaluated for the same; 3 patients had features of cholangitis. All the patients were managed successfully by endoscopic papillotomy and extraction of pancreatic calculi from the ampulla with resolution of biliary obstruction. CONCLUSION: Pancreatic calculus causing ampullary obstruction, though very rare, should be considered as a possibility in patients with CCP complicated by biliary obstruction. Endoscopic therapy is affective in the resolution of biliary obstruction in such patients.

Determination of influence of food intake after a single oral dose of mosapride in beagle dogs using nonlinear mixed effect modeling.

The objective of this study was to describe the population pharmacokinetics (PK) of mosapride under fasting and fed conditions. A single 5-mg oral dose of mosapride was administered to fasted (n = 15) and fed (n = 12) beagle dogs. Plasma concentrations of mosapride were subsequently measured by liquid chromatography-tandem mass spectrometry. Data were analyzed using modeling approaches with the NONMEM 7.2 software. A one-compartment open PK model utilizing model event time (MTIME) with first-order absorption and first-order elimination was found to be more appropriate than all other PK models tested. The absorption rate constants of mosapride were significantly decreased under fed conditions, compared to fasting conditions. The observed bootstrap medians of PK parameters were generally consistent with the corresponding population mean estimates. Furthermore, with the exception of some mosapride concentrations, most of observed data fell into the range of the 5th and 95th percentiles of the simulated values. Overall, the final model was able to describe the observed mosapride concentrations reasonably well. These findings suggest that food intake affects both the rate and extent of absorption of mosapride and that the pharmacological effect of mosapride can differ significantly depending on food intake.

Diagnosis of acute severe colitis.

It is important to assess the severity of ulcerative colitis (UC) in order to decide the intensity of treatment and predict outcome. The criteria instituted by Truelove and Witts almost 60 years back are still being used. However, they lack a scoring system and offer no clear definition for the moderate group. The criteria with scoring system and endoscopic criteria (Mayo Score) seems to be more useful clinically. Endoscopic assessment is very important and a cautious attempt should always be made even if it enables a limited colonoscopic examination. Proctosigmoidoscopy is advocated at initial stages and after 5 to 7 days. The criteria for severity in general are same for pan-colitis and limited disease.

Colorectal neoplasia in long-standing ulcerative colitis - a prospective study from a low-prevalence area.

AIM: Despite increasing recognition of ulcerative colitis (UC) in Asia in recent decades, reports on the occurrence of colorectal neoplasia (CRN) in UC are scarce and surveillance for this complication is not routinely practised in this region. We aimed to assess the outcome of a newly initiated pilot screening programme for screening CRN among UC patients in India. METHOD: In this prospective study from an academic hospital setting, patients with UC at high risk of CRN were offered screening by magnifying chromocolonoscopy and the frequency of neoplastic lesions was assessed. RESULTS: Twenty-nine (70.7%) of 41 eligible patients [a median age of 46 (interquartile range 36-54.5) years; 17 (58.6%) men] enrolled for surveillance; 41 colonoscopies were undertaken over 42 months. The median disease duration was 10 (interquartile range 7.5-14.5) years. Sixteen (55.1%) had extensive colitis. On initial screening, low-grade dysplasia (LGD) was seen in five (17.2%) and high-grade dysplasia (HGD) in three (10.3%). Of these three, one accepted proctocolectomy immediately, one underwent surgery for adenocarcinoma and one refused surgery. Twelve follow-up colonoscopies in nine patients revealed three new LGD. CONCLUSIONS: High-grade dysplasia and subsequent adenocarcinoma can be detected with careful follow-up in Indian patients with long-standing UC but acceptance of surveillance and subsequent therapy are suboptimal. We found evidence that screening and surveillance programmes are useful for detecting neoplasias in UC, and need to be customized for this region.

Assessing the Impact of Medication and Stenting on the Quality of Life of Patients With Chronic Pancreatitis: A Prospective Study.

This research aimed to assess the effect of pharmacotherapy alone versus the combination of pharmacotherapy and endoscopic stenting on the quality of life (QoL) outcomes of chronic pancreatitis patients. Chronic pancreatitis, an inflammatory disease, often presents with persistent pain, affecting patients' quality of life. Thirty patients treated either with pharmacotherapy alone or with the addition of endoscopic stenting were analyzed. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was used to gather data on the patients' QoL. Results showed that both treatment groups experienced improvements in global health, role functioning, fatigue, and abdominal pain scores over follow-ups. Specifically, the stenting group saw notable enhancements in global health and role functioning. The study's conclusions provide valuable insights into the potential benefits of both treatments, with stenting offering significant improvements in certain QoL parameters. However, the sample size and source limit generalizability, suggesting the need for more extensive research across diverse settings.

Uncovering sample heterogeneity in gaming and social withdrawal behaviors in adolescent and young adult gamers in Hong Kong.

OBJECTIVE: The current study aimed to examine the latent heterogeneity of gaming and social withdrawal behaviors in internet gamers and their associations with help-seeking behaviors. METHOD: The present study recruited 3430 young people (1874 adolescents and 1556 young adults) in Hong Kong in 2019. The participants completed the Internet Gaming Disorder (IGD) Scale, Hikikomori Questionnaire, and measures on gaming characteristics, depression, help-seeking, and suicidality. Factor mixture analysis was used to classify the participants into latent classes based on their latent factors of IGD and hikikomori in separate age groups. Latent class regressions examined the associations between help-seeking and suicidality. RESULTS: Both adolescents and young adults supported a 4-class, 2-factor model on gaming and social withdrawal behaviors. Over two-third of the sample were classified as healthy or low-risk gamers with low IGD factor means and low prevalence of hikikomori. Around one-fourth was moderate-risk gamers with elevated prevalence of hikikomori, higher IGD symptoms and psychological distress. A minority of the sample (3.8%-5.8%) belonged to high-risk gamers with the highest IGD symptoms and prevalence of hikikomori and heightened suicidal risks. Help-seeking in low-risk and moderate-risk gamers was positively associated with depressive symptoms and negatively associated with suicidal ideation. Perceived usefulness of help-seeking was significantly linked with lower likelihoods of suicidal ideation in the moderate-risk gamers and suicide attempt in the high-risk gamers. CONCLUSIONS: The present findings explicate the latent heterogeneity of gaming and social withdrawal behaviors and associated factors on help-seeking and suicidality among internet gamers in Hong Kong.

Effects of oxidant concentration and temperature on decolorization of azo dye: comparisons of UV/Fenton and UV/Fenton-like systems.

This study applies photo-Fenton and photo-Fenton-like systems to decolorize C.I. Reactive Red 2 (RR2). The oxidants were H(2)O(2) and Na(2)S(2)O(8); Fe(2+), Fe(3+), and Co(2+) were used to activate these two oxidants. The effects of oxidant concentration (0.3-2 mmol/L) and temperature (25-55 °C) on decolorization efficiency of the photo-Fenton and photo-Fenton-like systems were determined. The decolorization rate constants (k) of RR2 in the tested systems are consistent with pseudo-first-order kinetics. The rate constant increased as oxidant concentration and temperature increased. Activation energies of RR2 decolorization in the UV/H(2)O(2)/Fe(2+), UV/H(2)O(2)/Fe(3+), UV/Na(2)S(2)O(8)/Fe(2+) and UV/Na(2)S(2)O(8)/Fe(3+) systems were 32.20, 39.54, 35.54, and 51.75 kJ/mol, respectively.

Use of thiopurines in inflammatory bowel disease: an update.

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.