Saturated output of a Ge XXIII x-ray laser at 19.6 nm

We report on measurements of the saturated single frequency output of a Ge XXIII x-ray laser on the J=0-->1 transition at 19.6 nm from a refraction compensating double target driven by 150 J of energy from 75-ps Nd-glass laser pulses. The 19.6-nm line completely dominated the laser output. The output energy was measured to be 0.9 mJ in a beam of 6.6x30 mrad(2) divergence, corresponding to a conversion efficiency of 6 x 10(-6).

Using low and high prepulses to enhance the J=0-1 transition at 19.6 nm in the Ne-like germanium XUV laser

We report a study of the effect of prepulses on XUV lasing of Ne-like germanium for an irradiation geometry where approximate to 20 mm long germanium slab targets were irradiated at approximate to 1.6 x 10(13) W cm(-2) using approximate to 0.7 ns (1.06 mu m) pulses from the VULCAN glass laser. Prepulses were generated at fractional power levels of approximate to 2 x 10(-4) (low) and approximate to 2 x 10(-2) (high) and arrived on target 5 and 3.2 ns respectively in advance of the main heating pulse, For both the low and high prepulses the output of the 3p-3s, J = 0-1, line at 19.6 nm was enhanced such that the peak radiant density (J/st) for this line became greater than that for the normally stronger J = 2-1 lines at 23.2 and 23.6 nm. The J = 0-1 line, whose FWHM duration was reduced from approximate to 450 ps to approximate to 100 ps, delivered approximate to 6 x more power (W) than the average for the combined J = 2-1 lines, whose FWHM duration was approximate to 500 ps for both levels of prepulse, The higher prepulse was more effective, yielding approximate to 2 x more radiant density and approximate to 7 x more power on both the J = 0-1 and J = 2-1 transitions compared to the low prepulse case, The most dramatic observation overall was the approximate to 40 x increase of power in the J = 0-1 line for the high prepulse (approximate to 2%) case compared with the zero prepulse case. These observations, coupled with measurements of beam divergence and beam deviation through refractive bending, as well as general agreement with modelling, lead us to conclude that, for germanium, the main influence of the prepulse is (a) to increase the energy absorbed from the main pulse, (b) to increase the volume of the gain zone and (c) to relax the plasma density gradients, particularly in the J = 0-1 gain zone.

High contrast plasma mirror: spatial filtering and second harmonic generation at 10(19)Wcm(-2)

Recently, the use of plasma optics to improve temporal pulse contrast has had a remarkable impact on the field of high- power laser-solid density interaction physics. Opening an avenue to previously unachievable plasma density gradients in the high intensity focus, this advance has enabled researchers to investigate new regimes of harmonic generation and ion acceleration. Until now, however, plasma optics for fundamental laser reflection have been used in the sub-relativistic intensity regime (10(15) - 10(16)Wcm(-2)) showing high reflectivity (similar to 70%) and good focusability. Therefore, the question remains as to whether plasma optics can be used for such applications in the relativistic intensity regime (> 10(18)Wcm(-2)). Previous studies of plasma mirrors (PMs) indicate that, for 40 fs laser pulses, the reflectivity fluctuates by an order of magnitude and that focusability of the beam is lost as the intensity is increased above 5 x 10(16)Wcm(-2). However, these experiments were performed using laser pulses with a contrast ratio of similar to 10(7) to generate the reflecting surface. Here, we present results for PM operation using high contrast laser pulses resulting in a new regime of operation - the high contrast plasma mirror (HCPM). In this regime, pulses with contrast ratio > 10(10) are used to form the PM surface at > 10(19)Wcm(-2), displaying excellent spatial filtering, reflected near- field beam profile of the fundamental beam and reflectivities of 60 +/- 5%. Efficient second harmonic generation is also observed with exceptional beam quality suggesting that this may be a route to achieving the highest focusable harmonic intensities. Plasma optics therefore offer the opportunity to manipulate ultra-intense laser beams both spatially and temporally. They also allow for ultrafast frequency up-shifting without detrimental effects due to group velocity dispersion (GVD) or reduced focusability which frequently occur when nonlinear crystals are used for frequency conversion.

The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome

Most patients with acute myeloid leukaemia (AML) are older, with many unsuitable for conventional chemotherapy. Low-dose Ara-C (LDAC) is superior to best supportive care but is still inadequate. The combination of arsenic trioxide (ATO) and LDAC showed promise in an unrandomised study. We report a randomised trial of LDAC versus LDAC + ATO. Patients with AML according to WHO criteria or myelodysplastic syndrome with > 10% blasts, considered as unfit for conventional chemotherapy, were randomised between subcutaneous Ara-C (20mg b.d. for 10 days) and the same LDAC schedule with ATO (0.25 mg/kg) on days 1-5, 9 and 11, for at least four courses every 4 to 6 weeks. Overall 166 patients were entered; the trial was terminated on the advice of the DMC, as the projected benefit was not observed. Overall 14% of patients achieved complete remission (CR) and 7% CRi. Median survival was 5.5 months and 19 months for responders (CR: not reached; CRi: 14 months; non-responders: 4 months). There were no differences in response or survival between the arms. Grade 3/4 cardiac and liver toxicity, and supportive care requirements were greater in the ATO arm. This randomised comparison demonstrates that adding ATO to LDAC provides no benefit for older patients with AML. Leukemia (2011) 25, 1122-1127; doi:10.1038/leu.2011.59; published online 8 April 2011

Progress, challenges and perspectives in positron physics:Report on the XIIth international positron workshop

A report is presented of the XIIth International Workshop on Positron and Positronium Physics (Sandbjerg, Denmark, 19-21 July 2003). This workshop covered positron and positronium interactions with atoms, molecules and condensed matter systems. One key development reported was the first creation in the laboratory of low-energy antihydrogen atoms. Facets of positron-electron many-body systems were also considered, including the positronium molecule and BEC gases of positronium atoms. Aspects of the future of the field were discussed, including the development of new theoretical and experimental capabilities.

Automatic FPGA Synthesis of Memory Intensive C-based Kernels

Realising high performance image and signal processing
applications on modern FPGA presents a challenging implementation problem due to the large data frames streaming through these systems. Specifically, to meet the high bandwidth and data storage demands of these applications, complex hierarchical memory architectures must be manually specified
at the Register Transfer Level (RTL). Automated approaches which convert high-level operation descriptions, for instance in the form of C programs, to an FPGA architecture, are unable to automatically realise such architectures. This paper
presents a solution to this problem. It presents a compiler to automatically derive such memory architectures from a C program. By transforming the input C program to a unique dataflow modelling dialect, known as Valved Dataflow (VDF), a mapping and synthesis approach developed for this dialect can
be exploited to automatically create high performance image and video processing architectures. Memory intensive C kernels for Motion Estimation (CIF Frames at 30 fps), Matrix Multiplication (128x128 @ 500 iter/sec) and Sobel Edge Detection (720p @ 30 fps), which are unrealisable by current state-of-the-art C-based synthesis tools, are automatically derived from a C description of the algorithm.

All-cause mortality and periodontitis in 60-70-year-old men: A prospective cohort study

Objective To investigate the association between periodontitis and mortality from all causes in a prospective study in a homogenous group of 60- to 70-year-old West European men. Methodology A representative sample of 1400 dentate men, (mean age 63.8, SD 3.0 years), drawn from the population of Northern Ireland, had a comprehensive periodontal examination between 2001 and 2003. Men were divided into thirds on the basis of their mean periodontal attachment loss (PAL). The primary endpoint, death from any cause, was analysed using Kaplan-Meier survival plots and Cox's proportional hazards model. Results In total, 152 (10.9%) of the men died during a mean follow-up of 8.9 (SD 0.7) years; 37 (7.9%) men in the third with the lowest PAL (<1.8 mm) died compared with 73 (15.7%) in the third with the highest PAL (>2.6 mm). The unadjusted hazard ratio (HR) for death in the men with the highest level of PAL compared with those with the lowest PAL was 2.11 (95% CI 1.42-3.14), p < 0.0001. After adjustment for confounding variables (age, smoking, hypertension, BMI, diabetes, cholesterol, education, marital status and previous history of a cardiovascular event) the HR was 1.57 (1.04-2.36), p = 0.03. Conclusion The European men in this prospective cohort study with the most severe loss of periodontal attachment were at an increased risk of death compared with those with the lowest loss of periodontal attachment.

Lewis phenotype, secretor status, and coeliac disease

Patients who cannot secrete ABO and Lewis blood group antigens into body fluids, an ability controlled by a single gene on chromosome 19, are known to be at increased risk of certain autoimmune diseases associated with human leucocyte antigen (HLA) markers. This study investigated the possibility of an association with coeliac disease using red cell Lewis (Le) blood group phenotype to infer secretor status. Among 73 patients with coeliac disease who had Le a or b antigen, 48% were non-secretors (Le a + b-) compared with 27% of 137 blood donors (p = 0.004: odds ratio 2.49, 95% confidence intervals 1.37 to 4.51) and 26% of 62 medical and nursing staff controls (p = 0.014: odds ratio 2.65, 95% confidence intervals 1.27 to 5.50). Clinical characteristics did not differ between secretors and non-secretors with coeliac disease. Thus, the non-secretor state is significantly associated with coeliac disease, suggesting that genes on chromosome 19 may directly or indirectly participate in conferring susceptibility.

Bone-targeting radiopharmaceuticals including radium-223

ABSTRACT: Bone-seeking radionuclides including samarium-153 ethylene diamine tetramethylene phosphonate and strontium-89 have been used for decades in the palliation of pain from bone metastases especially from prostate cancer. Emerging evidence of improved survival in metastatic castration-resistant prostate cancer (CRPC) with the first-in-class a-radionuclide, radium-223 (Ra) has rekindled interest in the role of bone-seeking radionuclide therapy.We review the literature for randomized controlled trials of bone-seeking radionuclides and explore some of the issues regarding the optimal use of these agents. In particular, we discuss dose, dose rate, radiobiology, and quality of radiation and postulate on potential future directions in particular combination schedules. ß-Emitting, bone-seeking radionuclides have proven ability to control pain in prostate cancer metastatic to bone with pain response rates in the order of 60% to 70% when used as single agents. Most of the published trials were underpowered to detect differences in survival; however, there is evidence of the potential for disease modification when these agents are used in combination with chemotherapy or in multiple cycles.Data from the recent phase III ALSYMPCA trial that compared Ra to placebo in symptomatic CRPC demonstrate a significant improvement in median overall survival of 3.6 months for patients with symptomatic CRPC metastatic to bone treated with 6 cycles of the a-emitting radionuclide Ra compared with placebo. The success of Ra in improving survival in CRPC will lead this agent to become part of the treatment paradigm for this disease, and with such an excellent safety profile, Ra has huge potential in combination strategies as well as for use earlier in the natural history of metastatic prostate cancer.

Design of latch-based C-element

The C-element logic gate is a key component for constructing asynchronous control in silicon integrated circuits. The purpose of this reported work is to introduce a new speed-independent C-element design, which is synthesised by the asynchronous Petrify design tool to ensure it is composed of sequential digital latches rather than complex gates. The benefits are that it guarantees correct speed-independent operation, together with easy integration in modern design flows and processes. It is compared to an equivalent speed-independent complex gate C-element design generated by Petrify in a 130 nm semiconductor process.

The prevalence of primary angle closure glaucoma in European derived populations: a systematic review

AIM: To estimate the prevalence of primary angle closure glaucoma (PACG) in European derived populations.

METHOD: Systematic review and modelling of PACG prevalence data from population studies. PACG was defined according to the ISGEO definition requiring structural and/or functional evidence of glaucomatous optic neuropathy. Prevalence estimates were applied to the 2010 United Nations projected population figures to estimate case numbers.

RESULTS: The prevalence of PACG in those 40 years or more is 0.4% (95% CI 0.3% to 0.5%). Age-specific prevalence values are 0.02% (CI 0.00 to 0.08) for those 40-49 years, 0.60% (0.27 to 1.00) for those 50-59 years, 0.20% (0.06 to 0.42) for those 60-69 years and 0.94% (0.63 to 1.35) for those 70 years and older. Three-quarters of all cases occur in female subjects (3.25 female to 1 male; CI 1.76 to 5.94).

CONCLUSION: This analysis provides a current evidence-based estimate of PACG prevalence in European derived populations and suggests there are 130,000 people in the UK, 1.60 million people in Europe and 581,000 people in the USA with PACG today. Accounting for ageing population structures, cases are predicted to increase by 19% in the UK, 9% in Europe and 18% in the USA within the next decade. PACG is more common than previously thought, and all primary glaucoma cases should be considered to be PACG until the anterior chamber angle is shown to be open on gonioscopy.

The Novel Tubulin-Targeting Agent Pyrrolo-1,5-Benzoxazepine-15 Induces Apoptosis in Poor Prognostic Subgroups of Chronic Lymphocytic Leukemia

Pyrrolo-1,5-benzoxazepine-15 (PBOX-15) is a novel microtubule depolymerization agent that induces cell cycle arrest and subsequent apoptosis in a number of cancer cell lines. Chronic lymphocytic leukemia (CLL) is characterized by clonal expansion of predominately nonproliferating mature B cells. Here, we present data suggesting PBOX-15 is a potential therapeutic agent for CLL. We show activity of PBOX-15 in samples taken from a cohort of CLL patients (n = 55) representing both high-risk and low-risk disease. PBOX-15 exhibited cytotoxicity in CLL cells (n = 19) in a dose-dependent manner, with mean IC(50) of 0.55 mu mol/L. PBOX-15 significantly induced apoptosis in CLL cells (n = 46) including cells with poor prognostic markers: unmutated IgV(II) genes, CD38 and zeta-associated protein 70 (ZAP-70) expression, and fludarabine-resistant cells with chromosomal deletions in 17p. In addition, PBOX-15 was more potent than fludarabine in inducing apoptosis in fludarabine-sensitive cells. Pharmacologic inhibition and small interfering RNA knockdown of caspase-8 significantly inhibited PBOX-15-induced apoptosis. Pharmacologic inhibition of c-jun NH(2)-terminal kinase inhibited PBOX-15-induced apoptosis in mutated IgV(II) and ZAP-70(-) CLL cells but not in unmutated IgV(II) and ZAP-70(+) cells. PBOX-15 exhibited selective cytotoxicity in CLL cells compared with normal hematopoietic cells. Our data suggest that PBOX-15 represents a novel class of agents that are toxic toward both high-risk and low-risk CLL cells. The need for novel treatments is acute in CLL, especially for the subgroup of patients with poor clinical outcome and drug-resistant disease. This study identifies a novel agent with significant clinical potential.

Apolipoprotein C-III protein concentrations and gene polymorphisms in Type 1 diabetes:associations with microvascular disease complications in the DCCT/EDIC cohort

We investigated the associations of apolipoprotein C-III (apoCIII) protein and apoCIII gene variation with microvascular disease complications in Type 1 diabetes.