Reducing control noise in gravitational wave detectors with interferometric local damping of suspended optics.

Control noise is a limiting factor in the low-frequency performance of the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO). In this paper, we model the effects of using new sensors called Homodyne Quadrature Interferometers (HoQIs) to control the suspension resonances. We show that if we were to use HoQIs, instead of the standard shadow sensors, we could suppress resonance peaks up to tenfold more while simultaneously reducing the noise injected by the damping system. Through a cascade of effects, this will reduce the resonant cross-coupling of the suspensions, allow for improved stability for feed-forward control, and result in improved sensitivity of the detectors in the 10-20 Hz band. This analysis shows that improved local sensors, such as HoQIs, should be used in current and future detectors to improve low-frequency performance.

Sensors and actuators for the advanced LIGO A+ upgrade.

Advanced Laser Interferometer Gravitational-wave Observatory (LIGO A+) is a major upgrade to LIGO-the Laser Interferometer Gravitational-wave Observatory. For the A+ project, we have developed, produced, and characterized sensors and electronics to interrogate new optical suspensions designed to isolate optics from vibrations. The central element is a displacement sensor with an integrated electromagnetic actuator known as a BOSEM (Birmingham Optical Sensor and ElectroMagnetic actuator) and its readout and drive electronics required to integrate them into LIGO's control and data system. In this paper, we report on the improvements to the sensors and the testing procedures undertaken to meet the enhanced performance requirements set out by the A+ upgrade to the detectors. The best devices reach a noise level of 4.5 ×10-11m/Hz at a measurement frequency of 1 Hz, an improvement of 6.7 times over standard devices.

Widespread metastasis of a spermatocytic seminoma with concomitant hepatic peliosis in a Southern African hedgehog (Atelerix frontalis).

ABSTRACT: A six-year-old intact male Southern African hedgehog (Atelerix frontalis) presented with a history of chronic mild to moderate weight loss, and sub-acute hind limb ataxia that progressed to complete paralysis, at which point the hedgehog was euthanised. At autopsy, a large multinodular pale mass had completely replaced the left testicle and transcoelomically metastasised to the diaphragm and the peri-renal area, from where it then invaded the vertebral column and spinal cord. Multifocal, irregular to round, well-demarcated, blood-filled, proliferative lesions were also present in the hepatic parenchyma. Histological analysis of both the testis and metastatic lesions revealed diffuse sheets of neoplastic cells with moderate pale cytoplasm, large irregular to round nuclei and mostly one prominent magenta nucleolus, consistent with metastatic seminoma. The neoplastic cells were negative for periodic acid-Schiff (PAS) stain and positive for CD117 by immunohistochemistry (IHC). Taken together with the morphology of the neoplastic cells and the advanced age of the animal, this is suggestive of a spermatocytic seminoma. Histological analysis of the liver revealed multifocal lesions consisting of large anastomosing blood-filled spaces bordered by compressed hepatocytes, consistent with hepatic peliosis. This is the first report of a neoplasm in the Southern African hedgehog (Atelerix frontalis), the first report of a metastatic seminoma in a hedgehog, together with diagnosis of spermatocytic subtype, and the first report of a hedgehog with concomitant hepatic peliosis.

Prospective randomized trial of standard versus highly crosslinked tibial polyethylene in primary posterior-stabilized total knee arthroplasty: clinical and radiological follow-up at 2 to 11 years.

AIMS: There is insufficient evidence to recommend the use of alternative polyethylene bearings in modular, fixed-bearing total knee arthroplasty (TKA). The purpose of this study was to compare standard polyethylene (SP) and highly crosslinked polyethylene (XLP) tibial liners in posterior-stabilized TKA, with osteolysis as the primary outcome and clinical results and the rate of re-operation as the secondary outcomes. PATIENTS AND METHODS: This is a single-surgeon, prospective randomized study involving one design of modular posterior-stabilized TKA. An analysis of 122 TKAs with an SP compression moulded liner and 123 with an XLP liner was performed, with a mean follow-up of six years (2 to 11). Patients were evaluated clinically using the Knee Society score, Lower Extremity Activity Score (LEAS), and the presence of an effusion, and standard radiographs were assessed for radiolucent lines and osteolytic lesions. RESULTS: Osteolysis was present in four TKAs (3.3%) in the SP group, and no knees in the XLP group (p = 0.06). There were no significant differences between the Knee Society total score, change in total score, knee function score, change in function score, LEAS, and change in LEAS in the two groups. There was a significant difference in the presence of an effusion (10/122 with SP liners, 1/123 with XLP liners; p = 0.02). There was no significant difference in the rate of re-operation between the two groups (p = 0.36). There were no complications related to the XLP liner. CONCLUSION: At this length of follow-up, there were no advantages and no complications related to the use of this XLP tibial liner. The presence of effusion and small osteolytic lesions was more frequent with SP than XLP liners, but of unknown clinical significance. Cite this article: Bone Joint J 2019;101-B(7 Supple C):33-39.

Trunnion corrosion in metal-on-polyethylene hip arthroplasty: a simple diagnosis and treatment?

Aims: To report our experience with trunnion corrosion following metal-on-polyethylene total hip arthroplasty, in particular to report the spectrum of presentation and determine the mean time to presentation. Patients and Methods: We report the presenting symptoms and signs, intraoperative findings, and early results and complications of operative treatment in nine patients with a mean age of 74 years (60 to 86). The onset of symptoms was at a mean of seven years (3 to 18) after index surgery. Results: Patients presented with a variety of symptoms including pain, limp and rash. The preoperative mean serum cobalt level was 7.1 ppb (2.2 to 12.8) and mean serum chromium level was 2.2 ppb (0.5 to 5.2). Metal artifact reduction sequence (MARS) MRI showed fluid collection and possible pseudotumour formation in five hips, fluid collection in two hips, and synovitis/debris in one hip, with no MRI in one patient. Acetabular revision was performed in three patients, six patients underwent liner and head exchange only. The postoperative metal levels decreased in all patients: mean cobalt 0.5 ppb (0 to 1.8) and mean chromium 0.9 ppb (0 to 2.6) at a mean of five months (3 to 8) postoperatively. Seven patients had good pain relief and no complications at one year. There were two major complications requiring reoperation: acute infection at six weeks, for which the patient required two-stage reimplantation; and recurrent dislocation, for which the patient was revised to a dual mobility component. Conclusion: Trunnion corrosion in metal-on-polyethylene THA has a range of presenting symptoms, and may present later than previously described. A high index of suspicion is warranted, and serum cobalt and chromium levels are recommended for diagnosis. Patients should be counselled about possible postoperative complications. Cite this article: Bone Joint J 2018;100-B:898-902.

Design and Rationale for the Veterans Affairs "Cooperative Study Program 594 Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat" Trial.

BACKGROUND: Gout patients do not routinely achieve optimal outcomes related in part to suboptimal administration of urate lowering therapy (ULT) including first-line xanthine oxidase inhibitors allopurinol or febuxostat. Studies leading to the approval of febuxostat compared this agent to allopurinol in inappropriately low, fixed doses. We will compare allopurinol with febuxostat in gout using appropriately titrated doses of both agents and a "treat-to-target" strategy congruent with specialty guidelines. METHODS: We have planned and initiated the Veterans Affairs (VA) Cooperative Study Program (CSP) 594, Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study. This large double-blind, non-inferiority trial will enroll 950 gout patients randomized to receive allopurinol or febuxostat. Patients will be followed for a total of 72 weeks encompassing 3 distinct 24-week study phases. During Phase I (0-24 weeks), participants will undergo gradual dose titration of ULT until achievement of serum uric acid (sUA) <6.0 mg/dL or <5.0 mg/dL if tophi are present. Dose escalation will not be allowed during final three study visits of Phase 2 (24-48 weeks) and during Phase 3 (48-72 weeks). The primary study outcome is the proportion of participants experiencing at least one gout flare during Phase 3. Subsequent to the 72-week study, participants will be followed passively for up to 10 years after the study to assess long-term health outcomes. CONCLUSION: With its completion, the VA Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study will demonstrate the central role of gradual ULT dose escalation and a treat-to-target strategy in gout management.

Belimumab for the treatment of recalcitrant cutaneous lupus.

Background Belimumab is a monoclonal antibody that reduces B lymphocyte survival by blocking the binding of soluble human B lymphocyte stimulator (BLyS) to its B cell receptors. The utility of belimumab for management of resistant systemic lupus erythematosus (SLE) skin manifestations has not been reported. We present our experience of using this novel molecule for the successful management of cutaneous lupus at our center. Methods We studied five patients with significant SLE skin manifestations. All patients met 1997 American College of Rheumatology (ACR) SLE criteria and had failed multiple medications to control their skin disease. SLE disease activity indexes (SLEDAI), Cutaneous LE disease Area and Severity Index (CLASI) and patient's global assessment (PGA) were recorded before and 16 weeks after belimumab treatment. Belimumab was added to concomitant standard therapy. Results All five patients demonstrated marked clinical improvement subsequent to belimumab treatment. The average time to clinical improvement after treatment initiation was 8-12 weeks. SLEDAI scores (median, range) improved in all the patients ((2, 2-6) to (0, 0-4); p = 0.025). PGA scores (median, range) were better in all patients ((3, 2-3) to (1, 0-1); p = 0.039). CLASI activity scores (median, range) improved dramatically in all patients ((17, 9-31) to (3, 2-14); p = 0.043). There was no worsening of the CLASI damage scores. The mean daily prednisone dose decreased significantly from 31 mg (±18.8) at baseline to 3 mg (± 2.7) ( p = 0.042). Conclusion In this case series, the addition of belimumab to standard therapy improved the signs and symptoms of refractory cutaneous lupus. This is one of the first reports highlighting the potential utility of this medication for the treatment of severe skin involvement in SLE refractory to conventional therapies. Additional studies need to be performed to assess the use of belimumab in the treatment of cutaneous lupus.

Celastrol inhibits inflammatory stimuli-induced neutrophil extracellular trap formation.

Neutrophil extracellular traps (NETs) are web-like structures released by activated neutrophils. Recent studies suggest that NETs play an active role in driving autoimmunity and tissue injury in diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The purpose of this study was to investigate if celastrol, a triterpenoid compound, can inhibit NET formation induced by inflammatory stimuli associated with RA and SLE. We found that celastrol can completely inhibit neutrophil oxidative burst and NET formation induced by tumor necrosis factor alpha (TNFα) with an IC50 of 0.34 µM and by ovalbumin:anti-ovalbumin immune complexes (Ova IC) with an IC50 of 1.53 µM. Celastrol also completely inhibited neutrophil oxidative burst and NET formation induced by immunoglobulin G (IgG) purified from RA and SLE patient sera. Further investigating into the mechanisms, we found that celastrol treatment downregulated the activation of spleen tyrosine kinase (SYK) and the concomitant phosphorylation of mitogen-activated protein kinase kinase (MAPKK/MEK), extracellular-signal-regulated kinase (ERK), and NFκB inhibitor alpha (IκBα), as well as citrullination of histones. Our data reveals that celastrol potently inhibits neutrophil oxidative burst and NET formation induced by different inflammatory stimuli, possibly through downregulating the SYK-MEK-ERK-NFκB signaling cascade. These results suggest that celastrol may have therapeutic potentials for the treatment of inflammatory and autoimmune diseases involving neutrophils and NETs.

Left hemisphere diffusivity of the arcuate fasciculus: influences of autism spectrum disorder and language impairment.

BACKGROUND AND PURPOSE: There has been much discussion whether brain abnormalities associated with specific language impairment and autism with language impairment are shared or are disorder specific. Although white matter tract abnormalities are observed in both specific language impairment and autism spectrum disorders, the similarities and differences in the white matter abnormalities in these 2 disorders have not been fully determined. MATERIALS AND METHODS: Diffusion tensor imaging diffusion parameters of the arcuate fasciculus were measured in 14 children with specific language impairment as well as in 16 children with autism spectrum disorder with language impairment, 18 with autism spectrum disorder without language impairment, and 25 age-matched typically developing control participants. RESULTS: Language impairment and autism spectrum disorder both had (elevating) main effects on mean diffusivity of the left arcuate fasciculus, initially suggesting a shared white matter substrate abnormality. Analysis of axial and radial diffusivity components, however, indicated that autism spectrum disorder and language impairment differentially affect white matter microstructural properties, with a main effect of autism spectrum disorder on axial diffusivity and a main effect of language impairment on radial diffusivity. CONCLUSIONS: Although white matter abnormalities appear similar in language impairment and autism spectrum disorder when examining broad white matter measures, a more detailed analysis indicates different mechanisms for the white matter microstructural anomalies associated with language impairment and autism spectrum disorder.

Genetic variants associated with methotrexate efficacy and toxicity in early rheumatoid arthritis: results from the treatment of early aggressive rheumatoid arthritis trial.

Methotrexate (MTX) has emerged as first-line therapy for early moderate-to-severe rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. We tested the associations between 863 known pharmacogenetic variants and MTX response in 471 Treatment of Early Aggressive Rheumatoid Arthritis Trial participants with early RA. Efficacy and toxicity were modeled using multiple regression, adjusted for demographic and clinical covariates. Penalized regression models were used to test joint associations of markers and/or covariates with the outcomes. The strongest genetic associations with efficacy were in CHST11 (five markers with P<0.003), encoding carbohydrate (chondroitin 4) sulfotransferase 11. Top markers associated with MTX toxicity were in the cytochrome p450 genes CYP20A1 and CYP39A1, solute carrier genes SLC22A2 and SLC7A7, and the mitochondrial aldehyde dehydrogenase gene ALDH2. The selected markers explained a consistently higher proportion of variation in toxicity than efficacy. These findings could inform future development of personalized therapeutic approaches.

Elevated mean diffusivity in the left hemisphere superior longitudinal fasciculus in autism spectrum disorders increases with more profound language impairment.

BACKGROUND AND PURPOSE: Language impairments are observed in a subset of individuals with ASD. To examine microstructural brain white matter features associated with language ability in ASD, we measured the DTI parameters of language-related white matter tracts (SLF) as well as non-language-related white matter tracts (CST) in children with ASD/+LI and ASD/-LI) and in TD. MATERIALS AND METHODS: Eighteen children with ASD/-LI (age range, 6.7-17.5 years), 17 with ASD/+LI (age range, 6.8-14.8 years), and 25 TD (age range, 6.5-18 years) were evaluated with DTI and tractography. Primary DTI parameters considered for analysis were MD and FA. RESULTS: There was a main effect of diagnostic group on age-corrected MD (P < .05) with ASD/+LI significantly elevated compared with TD. This was most pronounced for left hemisphere SLF fiber tracts and for the temporal portion of the SLF. There was significant negative correlation between left hemisphere SLF MD values and the clinical assessment of language ability. There was no main effect of diagnostic group or diagnostic group X hemisphere interaction for FA. Although there was a main effect of diagnostic group on values of MD in the CST, this did not survive hemispheric subanalysis. CONCLUSIONS: Abnormal DTI parameters (specifically significantly elevated MD values in ASD) of the SLF appear to be associated with language impairment in ASD. These elevations are particularly pronounced in the left cerebral hemisphere, in the temporal portion of the SLF, and in children with clinical language impairment.

Nanostructural characteristics and mechanical properties of low temperature plasma enhanced chemical vapor deposited silicon nitride thin films.

This paper reports nanostructural characteristics and mechanical properties of the PECVD silicon nitride thin films deposited at relatively low temperatures. Nanostructures of the films were examined using high resolution transmission electron microscopy. Chemical bonding structures of the films were studied using Fourier Infrared Transmission Spectrum (FTIR) analysis. Mechanical properties of the films, such as creep behavior and frictional resistance, were investigated using nanoindentation and nanoscratch. The results showed that the variation in deposition temperature significantly affected the mechanical properties of the films, though all the films exhibited to have similar homogenous amorphous structures with no physical defect observed even at atomic scale. There existed strong correlations between the mechanical properties and the hydrogen concentration in the thin films.

Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations.

OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. CONCLUSION: These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations.

OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. CONCLUSIONS: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Magnetoencephalography for pediatric epilepsy: how we do it.

Magnetoencephalography (MEG) is increasingly being used in the preoperative evaluation of pediatric patients with epilepsy. The ability to noninvasively localize ictal onset zones (IOZ) and their relationships to eloquent functional cortex allows the pediatric epilepsy team to more accurately assess the likelihood of postoperative seizure freedom, while more precisely prognosticating the potential functional deficits that may be expected from resective surgery. Confirmation of clinically suggested multifocality may result in a recommendation against resective surgery because the probability of seizure freedom will be low. Current paradigms for motor and somatosensory testing are robust. Paradigms allowing localization of those regions necessary for competent language function, though promising, are under continuous optimization. MR imaging white matter trajectory data, created from diffusion tensor imaging obtained in the same setting as the localization brain MR imaging, provide ancillary information regarding connectivity of the IOZ to sites of rapid secondary spread and the spatial relationship of the IOZ to functionally important white matter bundles, such as the corticospinal tracts. A collaborative effort between neuroradiology, neurology, neurosurgery, neuropsychology, technology, and physics ensures successful implementation of MEG within a pediatric epilepsy program.

Comparison of two exercise protocols on fitness score improvement in poorly conditioned Air Force personnel.

A 12-wk. study was conducted to contrast the effects of a longer and more frequent aerobic exercise protocol with a shorter and less frequent circuit strength-training protocol for improving U.S. Air Force physical fitness test scores of subjects who previously failed to achieve a passing point total. 83 men and women of the U.S. Air Force (M age = 32.7 yr.) participated in either the unsupervised standard conditioning program, which recommended approximately 60 min. of aerobic activity 4 to 5 days per week (n=26), or the supervised circuit strength-training program, which required approximately 25 min. of alternating strength and endurance exercises 3 days per week (n=57). Subjects were assessed on a 2400-m (1.5-mile) run, abdominal circumference, push-ups completed in 1 min., and abdominal crunches completed in 1 min. Dependent t tests with Bonferroni adjustment indicated that significant improvements were attained by the circuit strength-training group only on each of the aforementioned measures. Significantly more participants in the circuit strength-training group (26%) achieved a passing point total than in the standard conditioning group (19%) at Wk. 12 (chi1(2) =3.96, p = .05). Implications for enhancing physical fitness in poorly conditioned adults were discussed.

Short-wavelength infrared tuneable filters on HgCdTe photoconductors.

The design, micro-fabrication, and electronic and optical performance of a tuneable short-wavelength infrared Fabry-Pérot microresonator on a mercury cadmium telluride photoconductor is presented. The maximum processing temperature of 125 degrees C has negligible effect on the electronic and optical performance of photoconductor test structures. Maximum responsivity, effective carrier lifetime and detectivity are 60x103 VW-1, 2x10-5 s and 8x1010 cmHz1/2W-1, respectively. The maximum effective carrier lifetime and specific detectivity are in good agreement with the theoretical maxima. Uncooled device operation is possible since responsivity is observed not to improve with thermo-electric cooling. Spectral tuning of the micro-filters is demonstrated over the wavelength range 1.7 to 2.2 mum using drive voltages up to 8 V, with the full-width-half-maximum of the resonance approximately 100 nm. Membrane deflection can be up to 40% of the cavity width.