An Optical Readout TPC (O-TPC) for Studies in Nuclear Astrophysics With Gamma-Ray Beams at HIgS

We report on the construction, tests, calibrations and commissioning of an Optical Readout Time Projection Chamber (O-TPC) detector operating with a CO2(80%) + N2(20%) gas mixture at 100 and 150 Torr. It was designed to measure the cross sections of several key nuclear reactions involved in stellar evolution. In particular, a study of the rate of formation of oxygen and carbon during the process of helium burning will be performed by exposing the chamber gas to intense nearly mono-energetic gamma-ray beams at the High Intensity Gamma Source (HIgS) facility. The O-TPC has a sensitive target-drift volume of 30x30x21 cm^3. Ionization electrons drift towards a double parallel grid avalanche multiplier, yielding charge multiplication and light emission. Avalanche induced photons from N2 emission are collected, intensified and recorded with a Charge Coupled Device (CCD) camera, providing two-dimensional track images. The event's time projection (third coordinate) and the deposited energy are recorded by photomultipliers and by the TPC charge-signal, respectively. A dedicated VME-based data acquisition system and associated data analysis tools were developed to record and analyze these data. The O-TPC has been tested and calibrated with 3.183 MeV alpha-particles emitted by a 148Gd source placed within its volume with a measured energy resolution of 3.0%. Tracks of alpha and 12C particles from the dissociation of 16O and of three alpha-particles from the dissociation of 12C have been measured during initial in-beam test experiments performed at the HIgS facility at Duke University. The full detection system and its performance are described and the results of the preliminary in-beam test experiments are reported.Comment: Supported by the Richard F. Goodman Yale-Weizmann Exchange Program, ACWIS, NY, and USDOE grant Numbers: DE-FG02-94ER40870 and DE-FG02-97ER4103

Semiclassical coherent state propagator for systems with spin

We derive the semiclassical limit of the coherent state propagator for systems with two degrees of freedom of which one degree of freedom is canonical and the other a spin. Systems in this category include those involving spin-orbit interactions and the Jaynes-Cummings model in which a single electromagnetic mode interacts with many independent two-level atoms. We construct a path integral representation for the propagator of such systems and derive its semiclassical limit. As special cases we consider separable systems, the limit of very large spins and the case of spin 1/2.Comment: 19 pages, no figure

Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4

The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer

Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.

The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage

The effects of beta-blockers on dobutamine-atropine stress echocardiography: early protocol versus standard protocol

BACKGROUND: To study the effects of Beta-blockers during Dobutamine Stress Echocardiography (DSE) comparing the hemodynamic benefits of an early administration of atropine in patients taking or not Beta-blockers. METHODS: One hundred and twenty-one patients were submitted to dobutamine stress echocardiography for the investigation of myocardial ischemia. The administration of atropine was randomized into two groups: A or B (early protocol when atropine was administered at 10 and 20 mcg/kg/min of dobutamine, respectively) and C (standard protocol with atropine at 40 mcg/kg/min of dobutamine). Analysis of the effects of Beta-blockers was done regarding the behavior pattern of heart rate and blood pressure, test time, number of conclusive and inconclusive (negative sub-maximum test) results, total doses of atropine and dobutamine, and general complications. RESULTS: Beta-blocked patients who received early atropine (Group A&B) had a significantly lower double product (p = 0.008), a higher mean test time (p = 0.010) and required a higher dose of atropine (p = 0.0005) when compared to the patients in this group who were not Beta-blocked. The same findings occurred in the standard protocol (Group C), however the early administration of atropine reduced test time both in the presence and absence of this therapy (p = 0.0001). The patients with Beta-blockers in Group A&B had a lower rate of inconclusive tests (26%) compared to those in Group C (40%). Complications were similar in both groups. CONCLUSION: The chronotropic response during dobutamine stress echocardiography was significantly reduced with the use of Beta-blockers. The early administration of atropine optimized the hemodynamic response, reduced test time in patients with or without Beta-blockers and reduced the number of inconclusive tests in the early protocol

Reliability and cultural applicability of the Greek version of the International Personality Disorders Examination.

BACKGROUND: The International Personality Disorders Examination (IPDE) constitutes the proposal of the WHO for the reliable diagnosis of personality disorders (PD). The IPDE assesses pathological personality and is compatible both with DSM-IV and ICD-10 diagnosis. However it is important to test the reliability and cultural applicability of different IPDE translations. METHODS: Thirty-one patients (12 male and 19 female) aged 35.25 ± 11.08 years, took part in the study. Three examiners applied the interview (23 interviews of two and 8 interviews of 3 examiners, that is 47 pairs of interviews and 70 single interviews). The phi coefficient was used to test categorical diagnosis agreement and the Pearson Product Moment correlation coefficient to test agreement concerning the number of criteria met. RESULTS: Translation and back-translation did not reveal specific problems. Results suggested that reliability of the Greek translation is good. However, socio-cultural factors (family coherence, work environment etc) could affect the application of some of the IPDE items in Greece. The diagnosis of any PD was highly reliable with phi >0.92. However, diagnosis of non-specfic PD was not reliable at all (phi close to 0) suggesting that this is a true residual category. Dianosis of specific PDs were highly reliable with the exception of schizoid PD. Diagnosis of antisocial and Borderline PDs were perfectly reliable with phi equal to 1.00. CONCLUSIONS: The Greek translation of the IPDE is a reliable instrument for the assessment of personality disorder but cultural variation may limit its applicability in international comparisons

Regional differences in psychiatric disorders in Chile

BACKGROUND: Psychiatric epidemiological surveys in developing countries are rare and are frequently conducted in regions that are not necessarily representative of the entire country. In addition, in large countries with dispersed populations national rates may have low value for estimating the need for mental health services and programs. METHODS: The Chile Psychiatric Prevalence Study using the Composite International Diagnostic Interview was conducted in four distinct regions of the country on a stratified random sample of 2,978 people. Lifetime and 12-month prevalence and service utilization rates were estimated. RESULTS: Significant differences in the rates of major depressive disorder, substance abuse disorders, non-affective psychosis, and service utilization were found across the regions. The differential prevalence rates could not be accounted by socio-demographic differences between sites. CONCLUSIONS: Regional differences across countries may exist that have both implications for prevalence rates and service utilization. Planning mental health services for population centers that span wide geographical areas based on studies conducted in a single region may be misleading, and may result in areas with high need being underserved

Amygdala Atrophy and Its Functional Disconnection with the Cortico-Striatal-Pallidal-Thalamic Circuit in Major Depressive Disorder in Females

Background Major depressive disorder (MDD) is approximately twice as common in females than males. Furthermore, female patients with MDD tend to manifest comorbid anxiety. Few studies have explored the potential anatomical and functional brain changes associated with MDD in females. Therefore, the purpose of the present study was to investigate the anatomical and functional changes underlying MDD in females, especially within the context of comorbid anxiety. Methods In this study, we recruited antidepressant-free females with MDD (N = 35) and healthy female controls (HC; N = 23). The severity of depression and anxiety were evaluated by the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Structural and resting-state functional images were acquired on a Siemens 3.0 Tesla scanner. We compared the structural volumetric differences between patients and HC with voxel-based morphometry (VBM) analyses. Seed-based voxel-wise correlative analyses were used to identify abnormal functional connectivity. Regions with structural deficits showed a significant correlation between gray matter (GM) volume and clinical variables that were selected as seeds. Furthermore, voxel-wise functional connectivity analyses were applied to identify the abnormal connectivity relevant to seed in the MDD group. Results Decreased GM volume in patients was observed in the insula, putamen, amygdala, lingual gyrus, and cerebellum. The right amygdala was selected as a seed to perform connectivity analyses, since its GM volume exhibited a significant correlation with the clinical anxiety scores. We detected regions with disrupted connectivity relevant to seed primarily within the cortico-striatal-pallidal-thalamic circuit. Conclusions Amygdaloid atrophy, as well as decreased functional connectivity between the amygdala and the cortico-striatal-pallidal-thalamic circuit, appears to play a role in female MDD, especially in relation to comorbid anxiety

The Effect of Interpersonal Psychotherapy and other Psychodynamic Therapies versus ‘Treatment as Usual’ in Patients with Major Depressive Disorder

Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Interpersonal psychotherapy and other psychodynamic therapies may be effective interventions for major depressive disorder, but the effects have only had limited assessment in systematic reviews.Cochrane systematic review methodology with meta-analysis and trial sequential analysis of randomized trials comparing the effect of psychodynamic therapies versus ‘treatment as usual’ for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included six trials randomizing a total of 648 participants. Five trials assessed ‘interpersonal psychotherapy’ and only one trial assessed ‘psychodynamic psychotherapy’. All six trials had high risk of bias. Meta-analysis on all six trials showed that the psychodynamic interventions significantly reduced depressive symptoms on the 17-item Hamilton Rating Scale for Depression (mean difference −3.12 (95% confidence interval −4.39 to −1.86;P<0.00001), no heterogeneity) compared with ‘treatment as usual’. Trial sequential analysis confirmed this result.We did not find convincing evidence supporting or refuting the effect of interpersonal psychotherapy or psychodynamic therapy compared with ‘treatment as usual’ for patients with major depressive disorder. The potential beneficial effect seems small and effects on major outcomes are unknown. Randomized trials with low risk of systematic errors and low risk of random errors are needed