Kernel Density Estimators for Axisymmetric Particle Beams

Bright beams are commonly represented by sampled data in the numerical algorithms used to simulate their properties. However, in these calculations and the analyses of their outputs, the beam’s density is sometimes required and must be calculated from the samples. Axisymmetric beams, which possess a rotational symmetry and are naturally expressed in polar coordinates, pose a particular challenge to density estimators. The area element in polar coordinates shrinks as the radius becomes small, and weighting the samples to account for their reduced frequency may cause unwelcome artifacts. In this work, we derive analytical expressions for two kernel density estimators, which solve these problems in the spatial coordinates and in the transverse phase space. We show how the kernels can be found by averaging the Gaussian kernel in Cartesian coordinates over the polar angle and demonstrate their use on test problems. These results show that particle beam symmetries can be taken advantage of in density estimation while avoiding artifacts

Early B Cell Factor Promotes B Lymphopoiesis with Reduced Interleukin 7 Responsiveness in the Absence of E2A

The basic helix-loop-helix transcription factors encoded by the E2A gene function at the apex of a transcriptional hierarchy involving E2A, early B cell factor (EBF), and Pax5, which is essential for B lymphopoiesis. In committed B lineage progenitors, E2A proteins have also been shown to regulate many lineage-associated genes. Herein, we demonstrate that the block in B lymphopoiesis imposed by the absence of E2A can be overcome by expression of EBF, but not Pax5, indicating that EBF is the essential target of E2A required for development of B lineage progenitors. Our data demonstrate that EBF, in synergy with low levels of alternative E2A-related proteins (E proteins), is sufficient to promote expression of most B lineage genes. Remarkably, however, we find that E2A proteins are required for interleukin 7–dependent proliferation due, in part, to a role for E2A in optimal expression of N-myc. Therefore, high levels of E protein activity are essential for the activation of EBF and N-myc, whereas lower levels of E protein activity, in synergy with other B lineage transcription factors, are sufficient for expression of most B lineage genes

A Primer on the Current State-of-the-Science Neoadjuvant and Adjuvant Therapy for Patients with Locally Advanced Rectal Adenocarcinomas

Patients with rectal cancers, due to the unique location of the tumor, have a recurrence pattern distinct from colon cancers. Advances in adjuvant therapy over the last three decades have played an important role in improving patient outcomes. This article serves to review the clinical studies that lay the basis for our current standard-of-care treatment of patients with locally advanced rectal cancer, as well as touch upon future ongoing experimental clinical trials of adjuvant chemoradiation therapy

Secondary prevention lifestyle interventions initiated within 90 days after TIA or 'minor' stroke: a systematic review and meta-analysis of rehabilitation programmes

Background Strokes are often preceded by a transient ischaemic attack (TIA) or ‘minor’ stroke. The immediate period after a TIA/minor stroke is a crucial time to initiate secondary prevention. However, the optimal approach to prevention, including non-pharmacological measures, after TIA is not clear. Aim To systematically review evidence about the effectiveness of delivering secondary prevention, with lifestyle interventions, in comprehensive rehabilitation programmes, initiated within 90 days of a TIA/minor stroke. Also, to categorise the specific behaviour change techniques used. Design and setting The review identified randomised controlled trials by searching the Cochrane Library, Ovid MEDLINE, Ovid EMBASE, Web of Science, EBSCO CINAHL and Ovid PsycINFO. Method Two review authors independently screened titles and abstracts for eligibility (programmes initiated within 90 days of event; outcomes reported for TIA/minor stroke) and extracted relevant data from appraised studies; a meta-analysis was used to synthesise the results. Results A total of 31 potentially eligible papers were identified and four studies, comprising 774 patients post-TIA or minor stroke, met the inclusion criteria; two had poor methodological quality. Individual studies reported increased aerobic capacity but meta-analysis found no significant change in resting and peak systolic blood pressure, resting heart rate, aerobic capacity, falls, or mortality. The main behaviour change techniques were goal setting and instructions about how to perform given behaviours. Conclusion There is limited evidence of the effectiveness of early post-TIA rehabilitation programmes with preventive lifestyle interventions. Further robust randomised controlled trials of comprehensive rehabilitation programmes that promote secondary prevention and lifestyle modification immediately after a TIA are needed

Coil-Assisted Retrograde Transvenous Obliteration (CARTO) for the Treatment of Portal Hypertensive Variceal Bleeding: Preliminary Results.

ObjectivesTo describe the technical feasibility, safety, and clinical outcomes of coil-assisted retrograde transvenous obliteration (CARTO) in treating portal hypertensive non-esophageal variceal hemorrhage.MethodsFrom October 2012 to December 2013, 20 patients who received CARTO for the treatment of portal hypertensive non-esophageal variceal bleeding were retrospectively evaluated. All 20 patients had at least 6-month follow-up. All patients had detachable coils placed to occlude the efferent shunt and retrograde gelfoam embolization to achieve complete thrombosis/obliteration of varices. Technical success, clinical success, rebleeding, and complications were evaluated at follow-up.ResultsA 100% technical success rate (defined as achieving complete occlusion of efferent shunt with complete thrombosis/obliteration of bleeding varices and/or stopping variceal bleeding) was demonstrated in all 20 patients. Clinical success rate (defined as no variceal rebleeding) was 100%. Follow-up computed tomography after CARTO demonstrated decrease in size with complete thrombosis and disappearance of the varices in all 20 patients. Thirteen out of the 20 had endoscopic confirmation of resolution of varices. Minor post-CARTO complications, including worsening of esophageal varices (not bleeding) and worsening of ascites/hydrothorax, were noted in 5 patients (25%). One patient passed away at 24 days after the CARTO due to systemic and portal venous thrombosis and multi-organ failure. Otherwise, no major complication was noted. No variceal rebleeding was noted in all 20 patients during mean follow-up of 384±154 days.ConclusionsCARTO appears to be a technically feasible and safe alternative to traditional balloon-occluded retrograde transvenous obliteration or transjugular intrahepatic portosystemic shunt, with excellent clinical outcomes in treating portal hypertensive non-esophageal variceal bleeding

Selective Effects of D- and L-Govadine in Preclinical Tests of Positive, Negative, and Cognitive Symptoms of Schizophrenia

There is a critical need to develop novel pharmacotherapeutics capable of addressing the positive, negative, and cognitive symptoms of schizophrenia. Building on recent studies with a racemic mixture of the synthetic tetrahydroprotoberberine, D,L-Govadine, we isolated the D- and L-stereoisomers and employed a battery of behavioral, neurochemical, and electrophysiological procedures to assess their individual therapeutic potential. Rodent models predictive of antipsychotic efficacy and those that model positive symptoms were employed and we found that L-Govadine, but not D-Govadine, improved these measures. Pretreatment with either stereoisomer during CS pre-exposure prevented the disruption of latent inhibition by amphetamine. Moreover, pretreatment with either stereoisomer also improved deficits in social interaction in the neonatal ventral hippocampal lesioned rat. Improved cognitive performance in two different prefrontal cortex-dependent tasks was observed with D-, but not L-Govadine, which strongly suggests that the D-steroisomer may be an effective cognitive enhancer. Alterations in dopamine efflux were also assessed and L-Govadine increased dopamine efflux in both the prefrontal cortex and nucleus accumbens. However, D-Govadine only increased dopamine efflux in the prefrontal cortex and not in the nucleus accumbens. Electrophysiological studies confirmed that L-Govadine is a DA-D2 antagonist, whereas D-Govadine shows no appreciable physiological effects at this receptor. Collectively these data show that L-Govadine performs well on measures predictive of antipsychotic efficacy and rodent models of positive symptoms through antagonism of DA-D2 receptors, whereas D-Govadine improves impairments in compromised memory function in delayed response tasks possibly through selective increases in DA efflux in the frontal cortex