Measurement of Electron Trapping in the CESR Storage Ring

The buildup of low-energy electrons has been shown to affect the performance of a wide variety of particle accelerators. Of particular concern is the persistence of the cloud between beam bunch passages, which can impose limitations on the stability of operation at high beam current. We have obtained measurements of long-lived electron clouds trapped in the field of a quadrupole magnet in a positron storage ring, with lifetimes much longer than the revolution period. Based on modeling, we estimate that about 7% of the electrons in the cloud generated by a 20-bunch train of 5.3 GeV positrons with 16-ns spacing and $1.3x10^{11}$ population survive longer than 2.3 $\mu$s in a quadrupole field of gradient 7.4 T/m. We have observed a non-monotonic dependence of the trapping effect on the bunch spacing. The effect of a witness bunch on the measured signal provides direct evidence for the existence of trapped electrons. The witness bunch is also observed to clear the cloud, demonstrating its effectiveness as a mitigation technique.Comment: 6 pages, 9 figures, 28 citation

Neighbourhood, Route and Workplace-Related Environmental Characteristics Predict Adults' Mode of Travel to Work

Commuting provides opportunities for regular physical activity which can reduce the risk of chronic disease. Commuters' mode of travel may be shaped by their environment, but understanding of which specific environmental characteristics are most important and might form targets for intervention is limited. This study investigated associations between mode choice and a range of objectively assessed environmental characteristics.Participants in the Commuting and Health in Cambridge study reported where they lived and worked, their usual mode of travel to work and a variety of socio-demographic characteristics. Using geographic information system (GIS) software, 30 exposure variables were produced capturing characteristics of areas around participants' homes and workplaces and their shortest modelled routes to work. Associations between usual mode of travel to work and personal and environmental characteristics were investigated using multinomial logistic regression.Of the 1124 respondents, 50% reported cycling or walking as their usual mode of travel to work. In adjusted analyses, home-work distance was strongly associated with mode choice, particularly for walking. Lower odds of walking or cycling rather than driving were associated with a less frequent bus service (highest versus lowest tertile: walking OR 0.61 [95% CI 0.20–1.85]; cycling OR 0.43 [95% CI 0.23–0.83]), low street connectivity (OR 0.22, [0.07–0.67]; OR 0.48 [0.26–0.90]) and free car parking at work (OR 0.24 [0.10–0.59]; OR 0.55 [0.32–0.95]). Participants were less likely to cycle if they had access to fewer destinations (leisure facilities, shops and schools) close to work (OR 0.36 [0.21–0.62]) and a railway station further from home (OR 0.53 [0.30–0.93]). Covariates strongly predicted travel mode (pseudo r-squared 0.74).Potentially modifiable environmental characteristics, including workplace car parking, street connectivity and access to public transport, are associated with travel mode choice, and could be addressed as part of transport policy and infrastructural interventions to promote active commuting

Glycemia and the Quality of Well-Being in Patients with Diabetes

Objectives : To investigate the cross-sectional relationships among self-reported frequencies of symptomatic hyperglycemia and hypoglycemia, HbA1c, and symptoms in the Quality of Well-Being Self-Administered (QWB-SA), and to examine the associations among these measures of glycemia and health utility scores. Research design and methods : The study group included 1522 patients with diabetes who attended University of Michigan Health System clinics. Published studies were reviewed to identify symptoms in the QWB-SA that might be associated with measures of glycemia. Linear regression analyses were performed to evaluate the strength of the associations among the frequency of self-reported measures of glycemia, QWB-SA symptoms, and QWB-SA-derived health utility scores. Results : Frequency of hyperglycemic symptoms was associated with 3% of the variance in the QWB-SA-derived health utility score in type 1 diabetes and with 5% of the variance in type 2 diabetes. Frequency of hypoglycemic symptoms was not associated with the QWB-SA-derived health utility score in type 1 diabetes but was associated with 1% of the variance in type 2 diabetes. HbA1c levels were not significantly associated with QWB-SA-derived health utility scores. After controlling for age, gender, and complications, frequency of hyperglycemic symptoms was significantly associated with QWB-SA-derived health utility scores in type 1 and type 2 diabetes. Conclusions : Reported frequency of hyperglycemic symptoms is associated with symptoms included in the QWB-SA and with QWB-SA-derived health utility scores. The QWB-SA may be an appropriate measure to assess the health burden of hyperglycemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43567/1/11136_2004_Article_5147235.pd

The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study

<p>Abstract</p> <p>Background</p> <p>We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (<it>LRRK2</it>)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen <it>LRRK2 </it>mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of <it>LRRK2 </it>mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD.</p> <p>Methods</p> <p>A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different <it>LRRK2 </it>mutations. Penetrance was estimated in families of <it>LRRK2 </it>carriers with consideration of the inherent bias towards increased penetrance in a familial sample.</p> <p>Results</p> <p>Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 <it>LRRK2 </it>mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the <it>LRRK2 </it>mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-<it>LRRK2</it>-related PD families.</p> <p>Conclusion</p> <p>Lifetime penetrance of <it>LRRK2 </it>estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained <it>LRRK2 </it>cases, suggesting that inherited susceptibility factors may modify the penetrance of <it>LRRK2 </it>mutations. In addition, the presence of nine PD phenocopies in the <it>LRRK2 </it>families suggests that these susceptibility factors may also increase the risk of non-<it>LRRK2</it>-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for <it>LRRK2 </it>carriers are independent of the factors which increase PD prevalence in men.</p

Lesion of the Cerebellar Noradrenergic Innervation Enhances the Harmaline-Induced Tremor in Rats

Abnormal synchronous activation of the glutamatergic olivo-cerebellar pathway has been suggested to be crucial for the harmaline-induced tremor. The cerebellum receives two catecholaminergic pathways: the dopaminergic pathway arising from the ventral tegmental area/substantia nigra pars compacta, and the noradrenergic one from the locus coeruleus. The aim of the present study was to examine a contribution of the cerebellar catecholaminergic innervations to the harmaline-induced tremor in rats. Rats were injected bilaterally into the cerebellar vermis with 6-hydroxydopamine (6-OHDA; 8 μg/0.5 μl) either alone or this treatment was preceded (30 min earlier) by desipramine (15 mg/kg ip). Harmaline was administered to animals in doses of 7.5 or 15 mg/kg ip. Tremor of forelimbs was measured as a number of episodes during a 90-min observation. Rats were killed by decapitation 30 or 120 min after harmaline treatment. The levels of dopamine, noradrenaline, serotonin, and their metabolites were measured by HPLC in the cerebellum, substantia nigra, caudate–putamen, and frontal cortex. 6-OHDA injected alone enhanced the harmaline-induced tremor. Furthermore, it decreased the noradrenaline level by ca. 40–80% in the cerebellum and increased the levels of serotonin and 5-HIAA in the caudate–putamen and frontal cortex in untreated and/or harmaline-treated animals. When 6-OHDA treatment was preceded by desipramine, it decreased dopaminergic transmission in some regions of the cerebellum while inducing its compensatory activation in others. The latter lesion did not markedly influence the tremor induced by harmaline. The present study indicates that noradrenergic innervation of the cerebellum interacts with cerebral serotonergic systems and plays an inhibitory role in the harmaline-induced tremor

Cognitive Behavioral Therapy versus Short Psychodynamic Supportive Psychotherapy in the outpatient treatment of depression: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Previous research has shown that Short Psychodynamic Supportive Psychotherapy (SPSP) is an effective alternative to pharmacotherapy and combined treatment (SPSP and pharmacotherapy) in the treatment of depressed outpatients. The question remains, however, how Short Psychodynamic Supportive Psychotherapy compares with other established psychotherapy methods. The present study compares Short Psychodynamic Supportive Psychotherapy to the evidence-based Cognitive Behavioral Therapy in terms of acceptability, feasibility, and efficacy in the outpatient treatment of depression. Moreover, this study aims to identify clinical predictors that can distinguish patients who may benefit from either of these treatments in particular. This article outlines the study protocol. The results of the study, which is being currently carried out, will be presented as soon as they are available.</p> <p>Methods/Design</p> <p>Adult outpatients with a main diagnosis of major depressive disorder or depressive disorder not otherwise specified according to DSM-IV criteria and mild to severe depressive symptoms (<it>Hamilton Depression Rating Scale </it>score ≥ 14) are randomly allocated to Short Psychodynamic Supportive Psychotherapy or Cognitive Behavioral Therapy. Both treatments are individual psychotherapies consisting of 16 sessions within 22 weeks. Assessments take place at baseline (week 0), during the treatment period (week 5 and 10) and at treatment termination (week 22). In addition, a follow-up assessment takes place one year after treatment start (week 52). Primary outcome measures are the number of patients refusing treatment (acceptability); the number of patients terminating treatment prematurely (feasibility); and the severity of depressive symptoms (efficacy) according to an independent rater, the clinician and the patient. Secondary outcome measures include general psychopathology, general psychotherapy outcome, pain, health-related quality of life, and cost-effectiveness. Clinical predictors of treatment outcome include demographic variables, psychiatric symptoms, cognitive and psychological patient characteristics and the quality of the therapeutic relationship.</p> <p>Discussion</p> <p>This study evaluates Short Psychodynamic Supportive Psychotherapy as a treatment for depressed outpatients by comparing it to the established evidence-based treatment Cognitive Behavioral Therapy. Specific strengths of this study include its strong external validity and the clinical relevance of its research aims. Limitations of the study are discussed.</p> <p>Trial registration</p> <p>Current Controlled Trails ISRCTN31263312</p

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Recent trends in the use of electrical neuromodulation in Parkinson's disease

Purpose of Review: This review aims to survey recent trends in electrical forms of neuromodulation, with a specific application to Parkinson’s disease (PD). Emerging trends are identified, highlighting synergies in state-of-the-art neuromodulation strategies, with directions for future improvements in stimulation efficacy suggested. Recent Findings: Deep brain stimulation remains the most common and effective form of electrical stimulation for the treatment of PD. Evidence suggests that transcranial direct current stimulation (tDCS) most likely impacts the motor symptoms of the disease, with the most prominent results relating to rehabilitation. However, utility is limited due to its weak effects and high variability, with medication state a key confound for efficacy level. Recent innovations in transcranial alternating current stimulation (tACS) offer new areas for investigation. Summary: Our understanding of the mechanistic foundations of electrical current stimulation is advancing and as it does so, trends emerge which steer future clinical trials towards greater efficacy