Time-Resolved Hard X-Ray Spectrometer

Wired array studies are being conducted at the SNL Z accelerator to maximize the x-ray generation for inertial confinement fusion targets and high energy density physics experiments. An integral component of these studies is the characterization of the time-resolved spectral content of the x-rays. Due to potential spatial anisotropy in the emitted radiation, it is also critical to diagnose the time-evolved spectral content in a space-resolved manner. To accomplish these two measurement goals, we developed an x-ray spectrometer using a set of high-speed detectors (silicon PIN diodes) with a collimated field-of-view that converged on a 1-cm-diameter spot at the pinch axis. Spectral discrimination is achieved by placing high Z absorbers in front of these detectors. We built two spectrometers to permit simultaneous different angular views of the emitted radiation. Spectral data have been acquired from recent Z shots for the radial and polar views. UNSPEC1 has been adapted to analyze and unfold the measured data to reconstruct the x-ray spectrum. The unfold operator code, UFO2, is being adapted for a more comprehensive spectral unfolding treatment

Signal Transmission in the Auditory System

Contains table of contents for Section 3, an introduction and reports on nine research projects.National Institutes of Health Grant 5 T32 NS07047National Institutes of Health Grant 5 P01 NS13126National Institutes of Health Grant 8 R01 DC00194National Institutes of Health Grant 5 R01 NS25995National Institutes of Health Grant 8 R01 DC00238National Institutes of Health Grant 5 R01 NS20322National Institutes of Health Grant 5 R01 DC00235National Institutes of Health Grant 5 R01 NS20269National Institutes of Health Grant 1 P01 NS23734Johnson and Johnson FoundationUnisys Corporation Doctoral Fellowshi

Planar wire array performance scaling at multi-MA levels on the Saturn generator.

A series of twelve shots were performed on the Saturn generator in order to conduct an initial evaluation of the planar wire array z-pinch concept at multi-MA current levels. Planar wire arrays, in which all wires lie in a single plane, could offer advantages over standard cylindrical wire arrays for driving hohlraums for inertial confinement fusion studies as the surface area of the electrodes in the load region (which serve as hohlraum walls) may be substantially reduced. In these experiments, mass and array width scans were performed using tungsten wires. A maximum total radiated x-ray power of 10 {+-} 2 TW was observed with 20 mm wide arrays imploding in {approx}100 ns at a load current of {approx}3 MA, limited by the high inductance. Decreased power in the 4-6 TW range was observed at the smallest width studied (8 mm). 10 kJ of Al K-shell x-rays were obtained in one Al planar array fielded. This report will discuss the zero-dimensional calculations used to design the loads, the results of the experiments, and potential future research to determine if planar wire arrays will continue to scale favorably at current levels typical of the Z machine. Implosion dynamics will be discussed, including x-ray self-emission imaging used to infer the velocity of the implosion front and the potential role of trailing mass. Resistive heating has been previously cited as the cause for enhanced yields observed in excess of jxB-coupled energy. The analysis presented in this report suggests that jxB-coupled energy may explain as much as the energy in the first x-ray pulse but not the total yield, which is similar to our present understanding of cylindrical wire array behavior

Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations and clinical impact

Recent evidence suggests that complex karyotype (CK) defined by the presence of 653 chromosomal aberrations (structural and/or numerical) identified by chromosome banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges towards routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with 655 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcome, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and or TP53 mutations, TP53abs) and the expression of somatically hypermutated (M-CLL) or unmutated (U-CLL) immunoglobulin heavy variable genes (IGHV). Thus, they contrasted CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs and IGHV gene somatic hypermutation status, we propose a novel hierarchical model where patients with high-CK exhibit the worst prognosis, while M-CLL lacking CK or TP53abs as well as CK with +12,+19 show the longest overall survival. In conclusion, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with 655 chromosomal aberrations emerges as prognostically adverse, independently of other biomarkers. Prospective clinical validation is warranted before finally incorporating high-CK in risk stratification of CLL

Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry

AIMS: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. METHODS AND RESULTS: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. CONCLUSION: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator

Barriers and enablers in the management of tuberculosis treatment in Addis Ababa, Ethiopia: a qualitative study

Tuberculosis (TB) is an infectious disease which causes about two million deaths each year. In 1993, the World Health Organization (WHO) declared TB to be a “Global Emergency” due to an increasing number of TB cases and a rise in multidrug resistant cases in the developed world. Treatment interruption was considered one of the major challenges. WHO introduced the current TB control program DOTS (directly observed treatment, short course) as the tool to control the disease. To prevent further development of resistance against anti-TB drugs it was decided to observe each patient taking their daily dose of medication. The overall aim of this thesis is to explore how patients and health workers perceive and manage TB symptoms and treatment in a high-endemic and a low-endemic setting in the era of DOT(S). The data is based on fieldwork, including in-depth interviews and focus groups with TB patients and health workers, in Addis Ababa, Ethiopia (2001-2002) and in Oslo/Akershus, Norway (2007-2008). We found that people’s interpretation and management of TB symptoms is influenced by cultural, social and economic factors. TB was, in both contexts, associated with poverty, and subsequently with a disease that affects certain countries or certain segments of a population. TB was viewed as a severe disease in both contexts, but there was variation between individuals to what extent one considered oneself as a likely victim. In the absence of circumstantial causes, such as poverty, patients in a lowendemic setting like Norway, found it difficult to understand why they had developed the disease. There was scarce knowledge about the fact that the disease could be latent. Awareness of early symptoms, such as persistent cough, was low in both contexts. Perceptions of vulnerability, together with the presence or absence of socio-economic barriers or enablers influenced at what time patients would seek help. The study suggests that health personnel lacked awareness or misinterpreted early symptoms of TB. In Ethiopia, lay categorizations of early TB symptoms converged with diagnostic practices in parts of the professional health sector. The diagnostic process could endure for many months after patients’ first contact with the health services. Similarly, in Norway, we found that patients’ interpretations of early symptoms often were confirmed in the meeting with health personnel. The consequences were prolonged diagnostic processes. The study shows that patients’ ability to manage TB treatment is a product of dynamic processes, in which social and economic costs and other burdens interplay over time. A decision to interrupt treatment can be shaped by past struggles and accrued costs; in which seems financially, socially or emotionally unbearable at the moment of treatment interruption. The burdens related to DOT could also be significant, in patients who did not interrupt treatment. Patients in both Ethiopia and Norway experienced an authoritarian and rigid practice of DOT, which made it difficult to simultaneously attend to demands related to treatment and demands related to other areas of life. The most vulnerable patients, such as those without permanent jobs, suffered from high economic, social and emotional costs. In conclusion, health personal need more knowledge about typical and atypical symptoms of TB. In low-endemic settings doctors need to be trained to adjust their level of suspicion to the migration history of the patient. In high-endemic settings one should be aware that health personnel may understand and manage TB within a traditional perspective. Patients in both high- and low-endemic contexts need concrete information about the cause of TB, how it is transmitted, how symptoms can be manifested, how the disease can progress and how it can be cured. The study indicates that inequalities that predispose for TB may be reinforced in the patient’s interaction with the health services due to a rigid, disempowering practice of DOT. Subsequently, DOT per se may add to the chain of structural barriers that patients have to overcome to access and complete treatment. To ensure that TB patients complete treatment one must address the coexisting and interacting crises that follow a TB diagnosis. This could require TB programs to adopt a more holistic approach. Measures that secure early diagnosis may reduce some of the physical, psycho-social and economic costs patients face while undergoing treatment. Measures that empower patients to participate in their own health care may avoid disempowering and humiliating practices

Compact Wire Array Sources: Power Scaling and Implosion Physics.

A series of ten shots were performed on the Saturn generator in short pulse mode in order to study planar and small-diameter cylindrical tungsten wire arrays at {approx}5 MA current levels and 50-60 ns implosion times as candidates for compact z-pinch radiation sources. A new vacuum hohlraum configuration has been proposed in which multiple z pinches are driven in parallel by a pulsed power generator. Each pinch resides in a separate return current cage, serving also as a primary hohlraum. A collection of such radiation sources surround a compact secondary hohlraum, which may potentially provide an attractive Planckian radiation source or house an inertial confinement fusion fuel capsule. Prior to studying this concept experimentally or numerically, advanced compact wire array loads must be developed and their scaling behavior understood. The 2008 Saturn planar array experiments extend the data set presented in Ref. [1], which studied planar arrays at {approx}3 MA, 100 ns in Saturn long pulse mode. Planar wire array power and yield scaling studies now include current levels directly applicable to multi-pinch experiments that could be performed on the 25 MA Z machine. A maximum total x-ray power of 15 TW (250 kJ in the main pulse, 330 kJ total yield) was observed with a 12-mm-wide planar array at 5.3 MA, 52 ns. The full data set indicates power scaling that is sub-quadratic with load current, while total and main pulse yields are closer to quadratic; these trends are similar to observations of compact cylindrical tungsten arrays on Z. We continue the investigation of energy coupling in these short pulse Saturn experiments using zero-dimensional-type implosion modeling and pinhole imaging, indicating 16 cm/?s implosion velocity in a 12-mm-wide array. The same phenomena of significant trailing mass and evidence for resistive heating are observed at 5 MA as at 3 MA. 17 kJ of Al K-shell radiation was obtained in one Al planar array fielded at 5.5 MA, 57 ns and we compare this to cylindrical array results in the context of a K-shell yield scaling model. We have also performed an initial study of compact 3 mm diameter cylindrical wire arrays, which are alternate candidates for a multi-pinch vacuum hohlraum concept. These massive 3.4 and 6 mg/cm loads may have been impacted by opacity, producing a maximum x-ray power of 7 TW at 4.5 MA, 45 ns. Future research directions in compact x-ray sources are discussed