Gravity gradient boom stabilization system for the Applications Technology Satellite /ATS-E/, volume 1 Final report

Gravity gradient boom stabilization system for ATS

Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study

Objectives. To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in patients with active PsA. Methods. Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP, presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures. Results. A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the secukinumab 300, 150 and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical improvements were observed through week 104 with secukinumab across other clinically important domains of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-a use. Over the entire treatment period the incidence, type and severity of adverse events were consistent with those reported previously. Conclusion. Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously. Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT0175263

Secukinumab versus adalimumab for psoriatic arthritis: comparative effectiveness up to 48 weeks using a matching-adjusted indirect comparison

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations. Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted). After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032). In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16-48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings. Novartis Pharma AG

Nanosecond laser texturing for high friction applications

AbstractA nanosecond pulsed Nd:YAG fibre laser with wavelength of 1064nm was used to texture several different steels, including grade 304 stainless steel, grade 316 stainless steel, Cr–Mo–Al ‘nitriding’ steel and low alloy carbon steel, in order to generate surfaces with a high static friction coefficient. Such surfaces have applications, for example, in large engines to reduce the tightening forces required for a joint or to secure precision fittings easily. For the generation of high friction textures, a hexagonal arrangement of laser pulses was used with various pulse overlaps and pulse energies. Friction testing of the samples suggests that the pulse energy should be high (around 0.8mJ) and the laser pulse overlap should be higher than 50% in order to achieve a static friction coefficient of more than 0.5. It was also noted that laser processing increases the surface hardness of samples which appears to correlate with the increase in friction. Energy-Dispersive X-ray spectroscopy (EDX) measurements indicate that this hardness is caused by the formation of hard metal-oxides at the material surface

Clinicopathological evidence that neovascularisation is a cause of recurrent varicose veins

Objectives:Recurrent varicose veins may result from poor initial surgical technique or progression of varicosities in collateral veins. In some cases new veins may develop at the saphenofemoral junction (neovascularisation) and cause recurrent saphenofemoral incompetence. This was a histological study of recurrent varicose veins.Design:This clinicopathological study included 20 patients (median age 55 years) who had surgery for recurrent saphenofemoral incompetence.Materials and methods:A total of 28 legs had groin re-exploration with repeat flush saphenofemoral ligation. The venous tissue block from the saphenofemoral region (including the proximal thigh varicosity) was excised and orientated for histological analysis. Evidence of neovascularisation was sought using routine histological sections and S100 immunohistochemistry.Results:At operation, thin-walled, serpentine neovascular veins were detected clinically as the principal cause of recurrence in 19 groins. In five groins recurrence was due to a residual missed vein at the saphenofemoral junction, and in four recurrence was caused by cross groin collaterals. On histological sections, evidence of neovascularisation was present in 27 of 28 groins. In eight it co-existed with the veins missed at the original operation but it was the sole identified cause of recurrent saphenofemoral incompetence in 19 (68%) groins.Conclusions:Neovascularisation was the principal cause of recurrent saphenofemoral incompetence in this series

The Fundamental Behavior of Timber-Concrete Composite Floors in Fire

Timber-concrete composite (TCC) floors have improved strength and stiffness when compared to timber-only floors, allowing for longer spans in buildings and improved life safety. However, North America does not have codes and standards that recognize TCC floors, particularly the improved life safety performance of these floors in fire. Therefore, alternate means and methods, structural fire engineering, or extensive structural testing is required for structural engineers to design the fire protection for TCC floors. This becomes a large burden on the building owner, as these calculation and testing methods are costly and add time to the project. The objective of this research is to fundamentally understand the behavior of TCC floors during a fire and benchmark existing analytical models for predicting the flexural capacity and deflection of TCC floors in fire against the experimentally collected data. This thesis presents an experimental investigation consisting of two experimental studies conducted to examine (1) properties of shear connectors used in TCC floors through ambient temperature direct shear tests and (2) the behavior of TCC floors through large-scale fire tests performed at the National Research Council (NRC) in Canada. An analytical investigation is performed consisting of benchmarking and improving existing analytical models for the prediction of flexural capacity and deflection of TCC floors during a standard fire. These models are benchmarked against experimental data from the experimental investigation and from previously published large-scale fire tests of TCC floors. The results indicate that TCC floors have improved fire performance when compared to mass timber floors. The calculated experimental char rates are comparable to prescribed char rates for timber-only, indicating existing char rates can be used for TCC floors. The presence of shear connectors and a concrete topping was found to have a negligible impact on the char rate of timber. Existing analytical models can reasonably predict the temperature-dependent flexural capacity and deflection of TCC floors in fires. This research quantifies the force-slip behavior of the shear connectors used as well as calculating the slip modulus of TCC floor shear connectors using the simplified design method (CEN 2004a). The use of both shear connector slip moduli demonstrated comparable results when calculating deflection using existing analytical models. The work presented in this thesis is intended to aid practicing engineers in the design of TCC floors for fire

Carbon bridged biphenolate ligands in rare earth chemistry

Rare earth biphenolate species have become an increasingly studied series of complexes, owing to the diversity they offer over mononuclear aryloxide complexes, as well as their efficacy as catalysts and initiators in a range of organic transformations and polymerisation reactions. Compared to monodentate aryloxide ligands, biphenolate ligand systems are still in their infancy in rare earth coordination chemistry. In their limited use, the ligand 2,2 '-methylenebis(6-tert-butyl-4-methylphenol) (mbmpH(2)) has been a popular candidate. This review aims to highlight the chemistry that has been explored thus far with these carbon bridged lanthanoid biphenolate systems

Effect of ammonium fluoride doping on the ice III to ice IX phase transition

Ice III is a hydrogen-disordered phase of ice that is stable between about 0.2 and 0.35 GPa. Upon cooling, it transforms to its hydrogen-ordered counterpart ice IX within the stability region of ice II. Here, the effect of ammonium fluoride doping on this phase transition is investigated, which is followed for the first time with in situ neutron diffraction. The a and c lattice constants are found to expand and contract, respectively, upon hydrogen ordering, yielding an overall negative volume change. Interestingly, the anisotropy in the lattice constants persists when ice IX is fully formed, and negative thermal expansion is observed. Analogous to the isostructural keatite and β-spodumenes, the negative thermal expansion can be explained through the buildup of torsional strain within the a–b plane as the helical “springs” within the structure expand upon heating. The reversibility of the phase transition was demonstrated upon heating. As seen in diffraction and Raman spectroscopy, the ammonium fluoride doping induces additional residual hydrogen disorder in ice IX and is suggested to be a chemical way for the “excitation” of the configurational ice-rules manifold. Compared to ice VIII, the dopant-induced hydrogen disorder in ice IX is smaller, which suggests a higher density of accessible configurational states close to the ground state in ice IX. This study highlights the importance of dopants for exploring the water’s phase diagram and underpins the highly complex solid-state chemistry of ice

Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis. Methods: In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01752634. Findings: Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6·81, 95% CI 3·42–13·56; p<0·0001), 150 mg (51 [51%] patients; 6·52, 3·25–13·08; p<0·0001), and 75 mg (29 [29%] patients; 2·32, 1·14–4·73; p=0·0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported. Interpretation: Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder