Phase modulation failsafe system for multi-kJ lasers based on optical heterodyne detection.

Amplification of the transverse scattered component of stimulated Brillouin scattering (SBS) can contribute to optical damage in the large aperture optics of multi-kJ lasers. Because increased laser bandwidth from optical phase modulation (PM) can suppress SBS, high energy laser amplifiers are injected with PM light. Phase modulation distributes the single-frequency spectrum of a master oscillator laser among individual PM sidebands, so a sufficiently high modulation index ß can maintain the fluence for all spectral components below the SBS threshold. To avoid injection of single frequency light in the event of a PM failure, a high-speed PM failsafe system (PMFS) must be employed. Because PM is easily converted to AM, essentially all PM failsafes detect AM, with the one described here employing a novel configuration where optical heterodyne detection converts PM to AM, followed by passive AM power detection. Although the PMFS is currently configured for continuous monitoring, it can also detect PM for pulse durations ≥2 ns and could be modified to accommodate shorter pulses. This PMFS was deployed on the Z-Beamlet Laser (ZBL) at Sandia National Laboratories, as required by an energy upgrade to support programs at Sandia's Z Facility such as magnetized liner inertial fusion. Depending on the origin of a PM failure, the PMFS responds in as little as 7 ns. In the event of an instantaneous failure during initiation of a laser shot, this response time translates to a 30-50 ns margin of safety by blocking a pulse from leaving ZBL's regenerative amplifier, which prevents injection of single frequency light into the main amplification chain. The performance of the PMFS, without the need for operator interaction, conforms to the principles of engineered safety.

The use of the mini C-arm in the outpatient setting: evolving practice.

The mini C-arm image intensifier (mini C-arm) has now become an established diagnostic tool in the hand surgery outpatient department. This study reviews the use of the mini C-arm and formal radiographs (X-rays) in the outpatient hand surgery setting. X-rays provide a standard image whereas the mini C-arm can obtain non-standard images to aid diagnosis and treatment. The mini C-arm enables the clinician to obtain dynamic images and perform interventions such as manipulations or injections. The mini C-arm results in a significantly lower radiation exposure for the patients than a formal X-ray. Use of the mini C-arm may be cheaper, and can lead to a shorter outpatient visit with less travel between hospital departments.

Rheumatoid arthritis patients with active disease and no history of cardiac pathology have higher brain natriuretic peptide (BNP) levels than patients with inactive disease or healthy control subjects.

BACKGROUND: Rheumatoid arthritis (RA) is associated with increased incidence cardiac failure. It is yet unclear how much the increased incidence is secondary to ischaemic damage, or whether inflammatory cytokines might have a direct effect on the myocardium. OBJECTIVES: To establish if patients with active rheumatoid arthritis but no history of cardiac disease have higher serum levels of brain natriuretic peptide (BNP), than patients with less active RA, or disease-free controls. METHODS: 90 patients with RA and 31 healthy control subjects were recruited. Each was screened to exclude previous history of cardiac disease. RA disease activity was measured using the DAS28 assessment, and other demographic, physical and laboratory tests performed. Serum BNP levels were measured in all subjects. RESULTS: There was no difference in the age, percentage females or BMI between the RA and control subjects. Median BNP in the RA patients was 80.0 pg/ml (IQR 38.0-132.0) compared with 48.5 (26.0-86.0) in the control subjects (p=0.017). There was a significant correlation between DAS28 and serum BNP in the RA group, r=0.37, p<0.01. RA patients were divided into three groups according to DAS28 scores. Patients with very active disease (DAS28>5.1) had significantly higher BNP levels than patients with moderately active disease (3.2

The benefit of radiologically-guided steroid injections for trapeziometacarpal osteoarthritis.

INTRODUCTION: Osteoarthritis of the trapeziometacarpal joint (TMJ) is a common condition causing significant disability. Conservative treatments include intra-articular steroid injections. PATIENTS AND METHODS: This clinical, observational study prospectively reviewed the longevity of benefit of steroid injections into the TMJ. Eighty-three patients were recruited with a median age of 62 years and injected with steroid and local anaesthetic under radioscopic guidance. They were followed up until the analgesic effects ceased with a questionnaire including visual analogue scores. RESULTS: Two-thirds of patients were improved at 2 months, with nearly half having a 3-month improvement. One in six patients had a 6-month benefit, with some patients still improved 2 years after injection. Previously injected patients had a reduced duration of benefit compared to their previous injection. Severity of osteoarthritis did not affect the injection efficacy. CONCLUSIONS: Based on this study, we recommend steroid injections in all degrees of TMJ osteoarthritis.

More than skin deep: atherosclerosis as a systemic manifestation of psoriasis.

There is now growing evidence that psoriasis, like other inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus, is a systemic disorder that is associated with enhanced atherosclerosis and risk of coronary artery disease. Here we summarize the available epidemiological evidence for this association and analyse pathogenic features that are common to psoriasis and atherosclerosis. Further prospective studies are urgently needed to extend knowledge of the risk of cardiovascular morbidity and mortality in patients with psoriasis and to confirm the degree to which treatment of psoriasis reduces this risk. Nevertheless, existing data are sufficient to indicate that severe psoriasis should be more widely recognized as a potential risk factor for cardiovascular disease and should be considered with the established factors when formulating strategies for the management of cardiovascular risk.

Polymorphisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX.

OBJECTIVE: To examine the role of adenosine receptor 2a gene (ADORA2a) polymorphisms on outcome of MTX treatment in RA. METHODS: Subjects included 309 RA patients with a defined response to MTX. Patients were included if they were (i) good responders (n = 147) (ESR <20 for >6/12 on stable dose of MTX) (ii) inefficacy failures (n = 101) (physician statement and failure to reduce ESR/CRP by 20%) or (iii) adverse event (AE) failures (n = 61) (verified by medical record review). AEs were sub-divided into gastrointestinal (GI) (n = 24), abnormal LFTs (n = 20) or other (n = 17). 8 single nucleotide polymorphisms (SNPs) within ADORA2a were genotyped using the Sequenom MALDI-TOF platform. RESULTS: Five SNPs within ADORA2a were associated with stopping MTX for AEs (OR 2.1-3.07, P < 0.05 for all). Analysis by AE type showed that the association was specific for GI toxicity. No association was observed between ADORA2a and inefficacy outcomes. CONCLUSION: Genetic variation within ADORA2a is significantly associated with AEs on MTX, specifically GI AEs. Knowledge of the ADORA2a genotype may help to improve identification of patients at high risk of GI toxicity with MTX.

Vitamin D deficiency is associated with anxiety and depression in fibromyalgia.

Fibromyalgia is a complex problem in which symptoms of anxiety and depression feature prominently. Low levels of vitamin D have been frequently reported in fibromyalgia, but no relationship was demonstrated with anxiety and depression. Seventy-five Caucasian patients who fulfilled the ACR criteria for fibromyalgia had serum vitamin D levels measured and completed the Fibromyalgia Impact Questionnaire (FIQ) and Hospital Anxiety and Depression Score (HADS). Deficient levels of vitamin D was found in 13.3% of the patients, while 56.0% had insufficient levels and 30.7% had normal levels. Patients with vitamin D deficiency (<25 nmol/l) had higher HADS [median, IQR, 31.0 (23.8-36.8] than patients with insufficient levels [25-50 nmol/l; HADS 22.5 (17.0-26.0)] or than patients with normal levels [50 nmol/l or greater; HADS 23.5 (19.0-27.5); Kruskal-Wallis ANOVA on ranks p<0.05]. There was no relationship with global measures of disease impact or musculoskeletal symptoms. Vitamin D deficiency is common in fibromyalgia and occurs more frequently in patients with anxiety and depression. The nature and direction of the causal relationship remains unclear, but there are definite implications for long-term bone health.

90% pump depletion and good beam quality in a pulse-injection-seeded nanosecond optical parametric oscillator.

We measured 90% pump depletion in a singly resonant image-rotating nanosecond optical parametric oscillator that was pulse-injection seeded by a self-generated signal pulse. The oscillator was pumped by an 8 ns duration single-frequency 532 nm pulse from an injection-seeded Q-switched Nd:YAG laser and resonated an 803 nm signal. The pump and pulsed-seed beams had flat-topped spatial fluence profiles with diameters of approximately 6 mm, giving a cavity Fresnel number at 803 nm approaching 400. The beam cleanup effects of the image-rotating cavity produce a far-field signal spatial fluence profile with approximately 60% of its energy falling within the diffraction-limited spot size.

Distinctive effects of G-CSF, GM-CSF and TNFalpha on neutrophil apoptosis in systemic lupus erythematosus.

OBJECTIVE: To investigate the influence of culture with G-CSF GM-CSF and TNFalpha on neutrophil apoptosis, comparing neutrophils from SLE patients with rheumatoid arthritis (RA) patients and healthy control subjects. METHODS: Neutrophils were isolated from SLE (n= 10), RA (n= 10) and healthy control subjects (n= 10), and cultured with two different concentrations of G-CSF, GM-CSF and TNFalpha. Proportion of apoptotic neutrophils at T=0, T=2hrs and T=24hrs was measured using FITC-labelled annexinV and flow cytometry. RESULTS: Significantly more neutrophils were apoptotic at T=0 in the SLE subjects than in the other groups (median, range--Control 3.5% (0.3-7.9) SLE 9.5% (2.9-29.1) RA 3.0% (0.4-23.0) p<0.05). Following culture for 24 hours with 1ng/ml G-CSF the proportion of apoptotic neutrophils from SLE subjects was significantly increased (median, range = 51.6% (27.0-84.0) without G-CSF v 66.8% (31.8-89.2) with G-CSF p<0.05). This was not observed with RA or control subjects, in whom the trend was towards inhibition of apoptosis. Similar trends were seen with GM-CSF There was significant induction of apoptosis in SLE neutrophils after 2 hr culture with 1ng/ml TNFalpha (median, range = 2.3% (0.1-8.0) without TNFalpha v 5.2% (1.0-22.4) with TNFalpha). No significant change was seen in the other groups. There was an inverse correlation between total neutrophil count and the degree of induction of apoptosis by G-CSF and GM-CSF, determined at a range of time-points and cytokine concentrations CONCLUSIONS: Neutrophils from SLE patients display resistance to the apoptosis-inhibiting effects of G-CSF and possibly GM-CSF, and appear more susceptible to the apoptosis-inducing action of TNFalpha, the greatest resistance being observed in the more neutropenic patients.