Planar laser induced fluorescence mapping of a carbon laser produced plasma.

We present measurements of ion velocity distribution profiles obtained by laser induced fluorescence (LIF) on an explosive laser produced plasma. The spatiotemporal evolution of the resulting carbon ion velocity distribution was mapped by scanning through the Doppler-shifted absorption wavelengths using a tunable, diode-pumped laser. The acquisition of these data was facilitated by the high repetition rate capability of the ablation laser (1 Hz), which allowed for the accumulation of thousands of laser shots in short experimental times. By varying the intensity of the LIF beam, we were able to explore the effects of fluorescence power against the laser irradiance in the context of evaluating the saturation vs the non-saturation regime. The small size of the LIF beam led to high spatial resolution of the measurement compared to other ion velocity distribution measurement techniques, while the fast-gate operation mode of the camera detector enabled the measurement of the relevant electron transitions.

Thomson scattering on the large plasma device.

We have developed a non-collective Thomson scattering diagnostic for measurements of electron density and temperature on the Large Plasma Device. A triple grating spectrometer with a tunable notch filter is used to discriminate the faint scattering signal from the stray light. In this paper, we describe the diagnostic and its calibration via Raman scattering and present the first measurements performed with the fully commissioned system. Depending on the discharge conditions, the measured densities and temperatures range from 4.0 × 1012 to 2.8 × 1013 cm-3 and from 1.2 to 6.8 eV, respectively. The variation of the measurement error with plasma parameters and discharges averaged is also discussed.

Raster Thomson scattering in large-scale laser plasmas produced at high repetition rate.

We present optical Thomson scattering measurements of electron density and temperature in a large-scale (∼2 cm) exploding laser plasma produced by irradiating a solid target with a high-energy (5-10 J) laser pulse at a high repetition rate (1 Hz). The Thomson scattering diagnostic matches this high repetition rate. Unlike previous work performed in single shots at much higher energies, the instrument allows for point measurements anywhere inside the plasma by automatically translating the scattering volume using motorized stages as the experiment is repeated at 1 Hz. Measured densities around 4 × 1016 cm-3 and temperatures around 7 eV result in a scattering parameter near unity, depending on the distance from the target. The measured spectra show the transition from collective scattering close to the target to non-collective scattering at larger distances. Densities obtained by fitting the weakly collective spectra agree to within 10% with an irradiance calibration performed via Raman scattering in nitrogen.

Durable benefit of rituximab maintenance post-autograft in patients with relapsed follicular lymphoma: 12-year follow-up of the EBMT lymphoma working party Lym1 trial.

We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10-13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40-54) with only 4 patients relapsing after 7.5 years. RM continues to significantly improve 10-year PFS after ASCT in comparison with NM [P = 0.002; HR 0.548 (95% CI 0.38-0.80)]. Ten-year non-relapse mortality (NRM) was not significantly different between treatment groups (7% overall). 10-year overall survival (OS) after ASCT was 75% (69-81) for the whole series, with no significant differences according to treatment sub-groups. 10-year OS for patients who progressed within 24 months (POD24T) was 60%, in comparison with 85% for patients without progression. Thus the benefit of rituximab maintenance after ASCT on relapse prevention is sustained at 12 years, suggesting that RM adds to ASCT-mediated disease eradication and may enhance the curative potential of ASCT.

Measurements of ion velocity distributions in a large scale laser-produced plasma.

Laser-produced plasma velocity distributions are an important, but difficult quantity to measure. We present a non-invasive technique for measuring individual charge state velocity distributions of laser-produced plasmas using a high temporal and spectral resolution monochromator. The novel application of this technique is its ability to detect particles up to 7 m from their inception (significantly larger than most laboratory plasma astrophysics experiments, which take place at or below the millimeter scale). The design and assembly of this diagnostic is discussed in terms of maximizing the signal to noise ratio, maximizing the spatial and temporal resolution, and other potential use cases. The analysis and results of this diagnostic are demonstrated by directly measuring the time-of-flight velocity of all ion charge states in a laser produced carbon plasma.

Measurement of temperature and density using non-collective X-ray Thomson scattering in pulsed power produced warm dense plasmas.

We present the first experimental measurement of temperature and density of a warm dense plasma produced by a pulsed power driver at the Nevada Terawatt Facility (NTF). In the early phases of discharge, most of the mass remains in the core, and it has been challenging to diagnose with traditional methods, e.g. optical probing, because of the high density and low temperature. Accurate knowledge of the transport coefficients as well as the thermodynamic state of the plasma is important to precisely test or develop theoretical models. Here, we have used spectrally resolved non-collective X-ray Thomson scattering to characterize the dense core region. We used a graphite load driven by the Zebra current generator (0.6 MA in 200 ns rise time) and the Ti He-α line produced by irradiating a Ti target with the Leopard laser (30 J, 0.8 ns) as an X-ray probing source. Using this configuration, we obtained a signal-to-noise ratio ~2.5 for the scattered signal. By fitting the experimental data with predicted spectra, we measured T = 2±1.9 eV, ρ = 0.6±0.5 gr/cc, 70 ns into the current pulse. The complexity of the dense core is revealed by the electrons in the dense core that are found to be degenerate and weakly coupled, while the ions remain highly coupled.

ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia-update on methodological approaches and results interpretation.

In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i.e., inhibitors of B-cell receptor (BcR) signaling and anti-apoptotic BCL2 family members, owing to their efficacy in patients with TP53 defects. In this report, the TP53 Network of the European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) presents updated recommendations on the methodological approaches for TP53 mutation analysis. Moreover, it provides guidance to ensure that the analysis is performed in a timely manner for all patients requiring treatment and that the data is interpreted and reported in a consistent, standardized, and accurate way. Since next-generation sequencing technologies are gaining prominence within diagnostic laboratories, this report also offers advice and recommendations for the interpretation of TP53 mutation data generated by this methodology.

Spatially resolved Thomson scattering measurements of the transition from the collective to the non-collective regime in a laser-produced plasma.

We present optical Thomson scattering results that image for the first time in a single measurement the spatial transition from collective to non-collective scattering. Data were taken in the Phoenix laser laboratory at the University of California, Los Angeles. The Raptor laser was used to ablate a carbon plasma, which was diagnosed with the frequency-doubled Phoenix laser serving as a Thomson scattering probe. Scattered light was collected from the laser plasma up to 10 cm from the target surface and up to 10 us after ablation, and imaged with high spatial and spectral resolutions. The results show a strong Thomson collective feature close to the target surface that smoothly transitions to a non-collective feature over several mm.

Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy: a Danish population-based study of 10455 patients.

The treatment of chronic lymphocytic leukemia (CLL) is in rapid transition, and during recent decades both combination chemotherapy and immunotherapy have been introduced. To evaluate the effects of this development, we identified all CLL patients registered in the nation-wide Danish Cancer Register between 1978 and 2013. We identified 10 455 CLL patients and 508 995 CLL-free control persons from the general population. Compared with the latter, the relative mortality rate between CLL patients and their controls decreased from 3.4 (95% CI 3.2-3.6) to 1.9 (95% CI 1.7-2.1) for patients diagnosed in 1978-1984 and 2006-2013, respectively. The improved survival corresponded to a decreasing risk of death from malignant hematological diseases, whereas the risk of death from infections was stable during the study period. These population-based data substantiate the improved survival for patients treated with chemo-immunotherapy demonstrated in clinical studies.

Protecting the Kidney in Liver Transplant Recipients: Practice-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice.

Both acute and chronic kidney disease are common after liver transplantation and result in significant morbidity and mortality. The introduction of the Model for End-stage Liver Disease score has directly correlated with an increased prevalence of perioperative renal dysfunction and the number of simultaneous liver-kidney transplantations performed. Kidney dysfunction in this population is typically multifactorial and related to preexisting conditions, pretransplantation renal injury, perioperative events, and posttransplantation nephrotoxic immunosuppressive therapies. The management of kidney disease after liver transplantation is challenging, as by the time the serum creatinine level is significantly elevated, few interventions affect the course of progression. Also, immunological factors such as antibody-mediated kidney rejection have become of greater interest given the rising liver-kidney transplant population. Therefore, this review, assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestine Community of Practice, provides a critical assessment of measures of renal function and interventions aimed at preserving renal function early and late after liver and simultaneous liver-kidney transplantation. Key points and practice-based recommendations for the prevention and management of kidney injury in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

Performance of five different bleeding-prediction scores in patients with acute pulmonary embolism.

Bleeding-prediction scores may help guiding management of patients with pulmonary embolism (PE), although no such score has been validated. We aimed to externally validate and compare two bleeding-prediction scores for venous thromboembolism to three scores developed for patients with atrial fibrillation in a real-world cohort of PE patients. We performed a prospective observational cohort study in 448 consecutive PE patients who were treated with heparins followed by vitamin-K-antagonists. The Kuijer, RIETE, HEMORR2HAGES, HAS-BLED and ATRIA scores were assessed at baseline. All patients were followed for the occurrence of major bleeding over a 30-day period. The accuracies of both the overall, original 3-level and newly defined optimal 2-level outcome of the scores were evaluated and compared, both for the 30-day period as well as for bleeding occurring in versus after the first week of treatment. 20 of 448 patients suffered major bleeding resulting in a cumulative incidence of 4.5 % (95 % CI 2.5-6.5). The predictive power of all five scores for bleeding was poor (c-statistics 0.57-0.64), both for the 3-level and 2-level score outcomes. No individual score was found to be superior. The HAS-BLED score had a good c-statistic for bleedings occurring after the first week of treatment (0.75, 95 % CI 0.47-1.0). Current available scoring systems have insufficient accuracy to predict overall anticoagulation-associated bleeding in patients treated for acute PE. To optimally target bleeding-prevention strategies, the development of a high quality PE-specific risk score is urgently needed.

The Impact of Hydroxyethyl Starch Use in Deceased Organ Donors on the Development of Delayed Graft Function in Kidney Transplant Recipients: A Propensity-Adjusted Analysis.

Our objective was to evaluate the impact of hydroxyethyl starch (HES) use in organ donors after neurologic determination of death (DNDD) on recipient renal graft outcomes. The following data elements were prospectively collected for every DNDD managed by a single organ procurement organization from June 2011 to July 2013: demographics; critical care endpoints; treatments, including the use of HES; graft cold ischemia time (CIT); and the occurrence of recipient delayed graft function (DGF, dialysis in the first week after transplantation). Logistic regression was performed to identify independent predictors of DGF with a p-value <0.05. The results were then adjusted for each donor's calculated propensity to receive HES. Nine hundred eighty-six kidneys were transplanted from 529 donors. Forty-two percent received HES (1217 ± 528 mL) and 35% developed DGF. Kidneys from DNDDs who received HES had a higher crude rate of DGF (41% vs. 31%, p < 0.001). After accounting for the propensity to receive HES, independent predictors of DGF were age (OR 1.02 [1.01-1.04] per year), CIT (OR 1.04[1.02-1.06] per hour), creatinine (OR 1.5 [1.32-1.72] per mg/dL) and HES use (OR 1.41 [1.02-1.95]). HES use during donor management was independently associated with a 41% increase in the risk of DGF in kidney transplant recipients.

A role for Rac1 activity in malignant progression of sebaceous skin tumors.

The small GTPase Rac1 is crucial for maintaining stem cells (SCs) in mammalian epidermis, and Rac1 activation leads to SC expansion. Loss or inhibition of Rac1 correlates with decreased frequency of skin cancer formation in a chemical carcinogenesis model. Here, we have addressed whether Rac1 activation would enhance carcinogenesis and result in tumor progression. We used K14ΔNLef1 mice, a model for differentiated sebaceous adenomas (SAs), and activated Rac1 in an epidermis-specific manner (K14L61Rac1). Surprisingly, Rac1 activation did not change the incidence and frequency of sebaceous tumors. However, tumors, which occurred exclusively in K14ΔNLef1/K14L61Rac1 double-transgenic mice, were poorly differentiated resembling malignant sebaceous tumors and were termed sebaceous carcinoma-like tumors (SCLTs). Compared with SAs, SCLTs showed an aberrant pattern of cell proliferation, invasive growth and less abundant expression of sebocyte differentiation markers, including stearoyl-CoA desaturase-1 and adipophilin. Interestingly, the adnexal SC marker Lrig1 was upregulated in SCLTs, showing that active Rac1 leads to the accumulation of sebocyte precursors in the context of K14ΔNLef1-induced skin tumors. In a search for targets of Rac1, we found cancer progression-related proteins, Dhcr24/Seladin1 and Nuclear protein 1/P8, to be strongly regulated in SCLTs. At last, Rac1 and Dhcr24/Seladin1 were detected in human sebaceous tumors demonstrating a potential high impact of our findings for human skin disease. This is the first study showing that Rac1 activity can lead to malignant progression of skin tumors.

Enhanced collisionless shock formation in a magnetized plasma containing a density gradient.

Two-dimensional hybrid simulations of super-Alfvénic expanding debris plasma interacting with an inhomogeneous ambient plasma are presented. The simulations demonstrate improved collisionless coupling of energy to the ambient ions when encountering a density gradient. Simulations of an expanding cylinder running into a step function gradient are performed and compared to a simple analytical theory. Magnetic flux probe data from a laboratory shock experiment are compared to a simulation with a more realistic debris expansion and ambient ion density. The simulation confirms that a shock is formed and propagates within the high density region of ambient plasma.

Exercise-induced changes in basal ganglia volume and cognition in older adults.

Physical activity has been demonstrated to diminish age-related brain volume shrinkage in several brain regions accompanied by a reduction of age-related decline in cognitive functions. Most studies investigated the impact of cardiovascular fitness or training. Other types of fitness or training are less well investigated. In addition, little is known about exercise effects on volume of the basal ganglia, which, however, are involved in motor activities and cognitive functioning. In the current study (1) we examined the relationships of individual cardiovascular and motor fitness levels with the volume of the basal ganglia (namely caudate, putamen, and globus pallidus) and selected cognitive functions (executive control, perceptual speed). (2) We investigated the effect of 12-month training interventions (cardiovascular and coordination training, control group stretching and relaxation) on the volume of the respective basal ganglia nuclei. Results revealed that motor fitness but not cardiovascular fitness was positively related with the volume of the putamen and the globus pallidus. Additionally, a moderating effect of the volume of the basal ganglia (as a whole, but also separately for putamen and globus pallidus) on the relationship between motor fitness and executive function was revealed. Coordination training increased caudate and globus pallidus volume. We provide evidence that coordinative exercise seems to be a favorable leisure activity for older adults that has the potential to improve volume of the basal ganglia.

Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study.

Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further investigation. Here we report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes (LNs), spleen and bone marrow, assessed phenotypic changes of circulating cells and measured whole-blood viscosity. With just one dose of ibrutinib, the average increase in ALC was 66%, and in>40% of patients the ALC peaked within 24 h of initiating treatment. Circulating CLL cells on day 2 showed increased Ki67 and CD38 expression, indicating an efflux of tumor cells from the tissue compartments into the blood. The kinetics and degree of the treatment-induced lymphocytosis was highly variable; interestingly, in patients with a high baseline ALC the relative increase was mild and resolution rapid. After two cycles of treatment the disease burden in the LN, bone marrow and spleen decreased irrespective of the relative change in ALC. Whole-blood viscosity was dependent on both ALC and hemoglobin. No adverse events were attributed to the lymphocytosis.

Pain characteristics and management of inpatients admitted to a comprehensive cancer centre: a cross-sectional study.

AIMS: This prospective, cross-sectional study aimed to assess cancer pain and its management in an inpatient setting at a comprehensive cancer centre in Denmark. METHODS: One hundred and eighty-eight inpatients with cancer were invited to participate (May/June 2011). Demographics, diagnoses, World Health Organization performance status, health-related quality of life, pain and data regarding analgesic treatment were registered. RESULTS: One hundred and thirty-four (71.3%) patients agreed to participate in the study. Most frequent diagnoses were leukaemia (27.6%) and lung cancer (14.2%). A high prevalence of pain was observed, 65.7%. Thirty-two per cent reported moderate to severe pain when it was at its worst, 96% reported no or mild pain when it was at its least. Nearly 22% reported moderate to severe pain when the pain was categorised as average. Breakthrough pain episodes were reported by 30.5%. Adjuvant medication was sparsely used and not always correctly indicated. Out of 88 patients with pain, 62.5% were left untreated according to the Electronic Medication System. Higher health-related quality of life was associated with lower pain intensity. The use of opioids with or without adjuvants was associated with higher pain intensity and higher number of breakthrough pain episodes. CONCLUSIONS: Approximately two thirds of inpatients reported pain and one third had breakthrough pain. A substantial number of patients with pain were left untreated. Opioid-treated patients reported highest pain intensity and number of breakthrough episodes; however, analgesic medication seemed to be underused. Measures to improve pain assessment and management are highly required.

Liver transplantation outcome in patients with angiographically proven coronary artery disease: a multi-institutional study.

Over the last decade the age of liver transplant (LT) recipients and the likelihood of coronary artery disease (CAD) in this population have increased. There are no multicenter studies that have examined the impact of CAD on LT outcomes. In this historical cohort study, we identified adult LT recipients who underwent angiography prior to transplantation at seven institutions over a 12-year period. For each patient we recorded demographic data, recipient and donor risk factors, duration of follow-up, the presence of angiographically proven obstructive CAD (≥50% stenosis) and post-LT survival. Obstructive CAD was present in 151 of 630 patients, the CAD(+) group. Nonobstructive CAD was found in 479 patients, the CAD(-) group. Patient survival was similar for the CAD(+) group (adjusted HR 1.13, CI = [0.79, 1.62], p = 0.493) compared to the CAD(-) group. The CAD(+) patients were further stratified into severe (CADsev, >70% stenosis, n = 96), and moderate CAD (CADmod, 50-70% stenosis, n = 55) groups. Survival for the CADsev (adjusted HR = 1.26, CI = [0.83, 1.91], p = 0.277) and CADmod (adjusted HR = 0.93, CI = [0.52, 1.66], p = 0.797) groups were similar to the CAD(-) group. We conclude that when current CAD treatment strategies are employed prior to transplant, post-LT survival is not significantly different between patients with and without obstructive CAD.

Magnetic field measurements in low density plasmas using paramagnetic Faraday rotator glass.

Paramagnetic Faraday rotator glass (rare-earth doped borosilicate) with a high Verdet constant will be used to measure the magnetic field inside of low density Helium plasmas (T(e) ~ 5 eV, T(i) ~ 1 eV) with a density of n ~ 10(12) cm(-3). Linearly polarized light is sent through the glass such that the plane of polarization is rotated by an angle that depends on the strength of the magnetic field in the direction of propagation and the length of the crystal (6 mm). The light is then passed into an analyzer and photo-detector setup to determine the change in polarization angle. This setup can detect magnetic fields up to 5 kG with a resolution of <5 G and a temporal resolution on the order of a nanosecond. The diagnostic will be used to characterize the structure and evolution of laser-driven collisionless shocks in large magnetized plasmas.