Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative.

OBJECTIVE: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). DESIGN: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if ≥80% of participants rated it ≥9 and as "optional" if ≥80% rated it ≥7. RESULTS: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. CONCLUSION: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context.

Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial.

BACKGROUND: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting. PATIENTS AND METHODS: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1 : 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response ≥50%, radiographic response, or stable disease ≥12 weeks). RESULTS: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001). CONCLUSIONS: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.

Usefulness of Dried Blood Spots (DBS) to perform hepatitis C virus genotyping in drug users in Senegal.

The aim of this pilot study was to analyze the Hepatitis C Virus (HCV) genotypes circulating in Senegal among Drug User (DUs), using Dried Blood Spots (DBS) as RNA source for molecular assays. Heroin and/or cocaine users (n = 506) were recruited in Dakar from April to July 2011, using a Respondent Driven Sampling (RDS) method. DBS preparation consisted of five drops of whole blood from finger applied to a Whatman paper card. HCV infection was screened by the detection of anti-HCV antibodies, using a rapid immune-chromatographic test. HCV RNA was quantified on anti-HCV positive DBS, using the Abbott RealTime HCV® Genotyping was performed on DBS with detectable viral load with Versant® HCV Genotype 2.0 Assay (LiPA) and Abbott RealTime HCV Genotype II assay®. Among the 506 participants, 120 were tested as positive for anti-HCV antibodies and their samples were analyzed for HCV RNA viral load and genotype. Out of the 120 DBS tested, HCV RNA was detected on 25 (20.8%). The median viral load was 15,058 IU/ml (ranging from 710 to 766,740 IU/ml). All positive DBS were suitable for the genotyping assay, that showed a predominance of genotype 1 (21/25) including 16 genotypes 1a and 5 genotypes 1b. HCV genotype 1 prevails in a DU population in Dakar. DBS could be useful for HCV RNA genotyping, but optimal storage conditions should required avoiding RNA impairment. Acknowledging this limitation, DBS could be a great interest for detecting and genotyping HCV viremic patients. J. Med. Virol. 89:484-488, 2017. © 2015 Wiley Periodicals, Inc.

The relationship between meniscal pathology and osteoarthritis depends on the type of meniscal damage visible on magnetic resonance images: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the association of different types of meniscal pathology with knee pain, bone marrow lesion (BML) volume, and end-stage knee osteoarthritis (esKOA). DESIGN: Participants were selected from an ancillary project to the Osteoarthritis Initiative (OAI) who had at least one knee with symptomatic osteoarthritis. Baseline magnetic resonance images (MRI) were evaluated for meniscal pathology using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) classification system. We collapsed 10 types of meniscal pathology into five categories: normal, intrameniscal signal, morphological deformity/extrusion (altered meniscal shape and/or extrusion but no apparent substance loss), tear, and maceration. Outcomes included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) knee pain and BML volume at baseline and after 2 years. We defined the prevalence of esKOA based on a validated algorithm. We performed logistic regression and adjusted for age, sex, and body mass index (BMI). RESULTS: The 463 participants (53% male) included in the analysis had mean age 63 (9.2) years, BMI 29.6 (4.6) kg/m2, and 71% had Kellgren-Lawrence grade ≥2. Morphological deformity/extrusion and maceration, but no other types of meniscal pathology, were associated with BML volume (morphological deformity/extrusion odds ratio [OR] = 2.47, 95% CI: 1.49, 4.09, maceration OR = 5.85, 95% CI: 3.40, 10.06) and change in BML volume (morphological deformity/extrusion OR = 2.17, 95% CI: 1.37, 3.45, maceration OR = 3.12, 95% CI: 1.87, 5.19). Only maceration was associated with baseline WOMAC knee pain (OR = 2.82, 95% CI: 1.79, 4.43) and prevalence of esKOA (OR = 7.53, 95% CI: 4.25, 13.31). CONCLUSIONS: Based on MRI, morphologic deformity/extrusion and maceration rather than intrameniscal signal or tear were associated with osteoarthritis severity and progression, which highlights the importance of differentiating distinct types of meniscal pathology.

Silicon photonic integrated circuits with electrically programmable non-volatile memory functions.

Conventional silicon photonic integrated circuits do not normally possess memory functions, which require on-chip power in order to maintain circuit states in tuned or field-configured switching routes. In this context, we present an electrically programmable add/drop microring resonator with a wavelength shift of 426 pm between the ON/OFF states. Electrical pulses are used to control the choice of the state. Our experimental results show a wavelength shift of 2.8 pm/ms and a light intensity variation of ~0.12 dB/ms for a fixed wavelength in the OFF state. Theoretically, our device can accommodate up to 65 states of multi-level memory functions. Such memory functions can be integrated into wavelength division mutiplexing (WDM) filters and applied to optical routers and computing architectures fulfilling large data downloading demands.

Is pain from mammography reduced by the use of a radiolucent MammoPad? Local experience in Hong Kong.

INTRODUCTION: Screening mammogram can decrease the mortality of breast cancer. Studies show that women avoid mammogram because of fear of pain, diagnosis, and radiation. This study aimed to evaluate the effectiveness of a radiolucent pad (MammoPad; Hologic Inc, Bedford [MA], US) during screening mammogram to reduce pain in Chinese patients and the possibility of glandular dose reduction. METHODS: This case series was conducted in a private hospital in Hong Kong. Between November 2011 and January 2012, a total of 100 Chinese patients were recruited to our study. Left mammogram was performed without MammoPad and served as a control. Right mammogram was performed with the radiolucent MammoPad. All patients were then requested to complete a simple questionnaire. The degree of pain and discomfort was rated on a 0-10 numeric analogue scale. Significant reduction in discomfort was defined as a decrease of 10% or more. RESULTS: Of the 100 patients enrolled in this study, 66.3% of women reported at least a 10% reduction in the level of discomfort with the use of MammoPad. No statistical differences between age, breast size, and the level of discomfort were found. CONCLUSION: The use of MammoPad significantly reduced the level of discomfort experienced during mammography. Radiation dose was also reduced.

Highly spectrum-selective ultraviolet photodetector based on p-NiO/n-IGZO thin film heterojunction structure.

Ultraviolet photodetector with p-n heterojunction is fabricated by magnetron sputtering deposition of n-type indium gallium zinc oxide (n-IGZO) and p-type nickel oxide (p-NiO) thin films on ITO glass. The performance of the photodetector is largely affected by the conductivity of the p-NiO thin film, which can be controlled by varying the oxygen partial pressure during the deposition of the p-NiO thin film. A highly spectrum-selective ultraviolet photodetector has been achieved with the p-NiO layer with a high conductivity. The results can be explained in terms of the "optically-filtering" function of the NiO layer.

Slot waveguide ring resonators coated by an atomic layer deposited organic/inorganic nanolaminate.

In this study, slot waveguide ring resonators patterned on a silicon-on-insulator (SOI) wafer and coated with an atomic layer deposited nanolaminate consisting of alternating layers of tantalum pentoxide and polyimide were fabricated and characterized. To the best of our knowledge, this is the first demonstration of atomic layer deposition (ALD) of organic materials in waveguiding applications. In our nanolaminate ring resonators, the optical power is not only confined in the narrow central air slot but also in several parallel sub-10 nm wide vertical polyimide slots. This indicates that the mode profiles in the silicon slot waveguide can be accurately tuned by the ALD method. Our results show that ALD of organic and inorganic materials can be combined with conventional silicon waveguide fabrication techniques to create slot waveguide ring resonators with varying mode profiles. This can potentially open new possibilities for various photonic applications, such as optical sensing and all-optical signal processing.

[Evaluation of microalbuminuria and lipid profile among type 2 diabetics]. / Evaluation de la microalbuminurie et du profil lipidique chez les diabétiques de type 2.

OBJECTIVE: To establish the respective prevalence of microalbuminuria and dyslipidemia and to evaluate their association with diabetes type 2. ANALYZE DATA: Prospective study of 195 type 2 diabetic subjects (125 women and 70 men) from a hospital in the city of Dakar (Senegal) for a check-up of diabetes. Age and sex were determined ; fasting blood glucose, glycated hemoglobin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and micro- albuminuria were measured. RESULTS: In this study, the mean age of patients was 57.9 ± 11.1 years. Age, glycated hemoglobin and microalbuminuria were significantly higher in women than in men (P < 0.01 ; P < 0.03 ; P < 0.01 respectively). The prevalence of microalbuminuria is 48.7% and that of dyslipidemia is 41.1%. Glycated hemoglobin is higher in subjects with microalbuminuria than in patients with normal microalbuminuria with a statistically significant difference (P < 0.001). There is a strong correlation (R = 0.82) between glycated hemoglobin and microalbuminuria, 1% increase in HbA1c corresponding approximately to an increase of 39.7 mg/I of microalbuminuria. CONCLUSION: Microalbuminuria and dyslipidemia are frequently found in type 2 diabetes, but the pathophysiological mechanisms of the association are not well known.

Design of an ultra-compact electro-absorption modulator comprised of a deposited TiN/HfO2/ITO/Cu stack for CMOS backend integration.

An ultra-compact electro-absorption (EA) modulator operating around 1.55-µm telecom wavelengths is proposed and theoretically investigated. The modulator is comprised of a stack of TiN/HfO2

Silicon photonics packaging with lateral fiber coupling to apodized grating coupler embedded circuit.

We report a novel lateral packaging approach using laser welding technique with angle polished fiber coupling to grating coupler embedded silicon photonic circuit. Measurements show the relax alignment tolerance for fiber packaging process. The packaging excess loss of 1.2 dB is achieved. The use of angle polished fiber for lateral fiber coupling enables an alternative way for cost-effective deployment of silicon photonics packaging in telecommunication systems.

Efficient silicon nitride grating coupler with distributed Bragg reflectors.

In this paper we have designed, fabricated and characterized a high efficiency Silicon nitride grating coupler at 1490 nm. Distributed Bragg reflectors as bottom mirrors are employed to improve the coupling efficiency by reflecting the downward traveling light. The peak coupling efficiency obtained is about -2.5 dB and the 1-dB bandwidth is 53 nm. The fabrication process is CMOS-compatible and is ready to be integrated with photonic circuits.

CMOS-compatible high efficiency double-etched apodized waveguide grating coupler.

We present a high efficiency double-etched apodized fiber-to-waveguide grating coupler on a silicon-on-insulator substrate, which can be fabricated using deep UV photolithography. The fabricated grating coupler yields a coupling loss of -1.5 dB with 3-dB bandwidth of 54 nm at a wavelength of 1560 nm. Measurements and simulations show that the double-etched apodized grating coupler design is robust and tolerant to fabrication process variations.

Phase modulation in horizontal metal-insulator-silicon-insulator-metal plasmonic waveguides.

An extremely compact Si phase modulator is proposed and validated, which relies on effective modulation of the real part of modal index of horizontal metal-insulator-Si-insulator-metal plasmonic waveguides by a voltage applied between the metal cover and the Si core. Proof-of-concept devices are fabricated on silicon-on-insulator substrates using standard complementary metal-oxide-semiconductor technology using copper as the metal and thermal silicon dioxide as the insulator. A modulator with a 1-µm-long phase shifter inserted in an asymmetric Si Mach-Zehnder interferometer exhibits 9-dB extinction ratio under a 6-V/10-kHz voltage swing. Numerical simulations suggest that high speed and low driving voltage could be achieved by shortening the distance between the Si core and the n(+)-contact and by using a high-κ dielectric as the insulator, respectively.

Silicon nitride based plasmonic components for CMOS back-end-of-line integration.

Silicon nitride waveguides provide low propagation loss but weak mode confinement due to the relatively small refractive index contrast between the Si3N4 core and the SiO2 cladding. On the other hand, metal-insulator-metal (MIM) plasmonic waveguides offer strong mode confinement but large propagation loss. In this work, MIM-like plasmonic waveguides and passive devices based on horizontal Cu-Si3N4-Cu or Cu-SiO2-Si3N4-SiO2-Cu structures are integrated in the conventional Si3N4 waveguide circuits using standard CMOS backend processes, and are characterized around 1550-nm telecom wavelengths using the conventional fiber-waveguide-fiber method. The Cu-Si3N4(~100 nm)-Cu devices exhibit ~0.78-dB/µm propagation loss for straight waveguides, ~38% coupling efficiency with the conventional 1-µm-wide Si3N4 waveguide through a 2-µm-long taper coupler, ~0.2-dB bending loss for sharp 90° bends, and ~0.1-dB excess loss for ultracompact 1 × 2 and 1 × 4 power splitters. Inserting a ~10-nm SiO2 layer between the Si3N4 core and the Cu cover (i.e., the Cu-SiO2(~10 nm)-Si3N4(~100 nm)-SiO2(~10 nm)-Cu devices), the propagation loss and the coupling efficiency are improved to ~0.37 dB/µm and ~52% while the bending loss and the excess loss are degraded to ~3.2 dB and ~2.1 dB, respectively. These experimental results are roughly consistent with the numerical simulation results after taking the influence of possible imperfect fabrication into account. Ultracompact plasmonic ring resonators with 1-µm radius are demonstrated with an extinction ratio of ~18 dB and a quality factor of ~84, close to the theoretical prediction.

Theoretical investigation of ultracompact and athermal Si electro-optic modulator based on Cu-TiO2-Si hybrid plasmonic donut resonator.

An ultracompact silicon electro-optic modulator operating at 1550-nm telecom wavelengths is proposed and analyzed theoretically, which consists of a Cu-TiO(2)-Si hybrid plasmonic donut resonator evanescently coupled with a conventional Si channel waveguide. Owing to a negative thermo-optic coefficient of TiO(2) (~-1.8 × 10(-4) K(-1)), the real part of effective modal index of the curved Cu-TiO(2)-Si hybrid waveguide can be temperature-independent (i.e., athermal) if the TiO(2) interlayer and the beneath Si core have a certain thickness ratio. A voltage applied between the ring-shaped Cu cap and a cylinder metal electrode positioned at the center of the donut,--which makes Ohmic contact to Si, induces a ~1-nm-thick free-electron accumulation layer at the TiO(2)/Si interface. The optical field intensity in this thin accumulation layer is significantly enhanced if the accumulation concentration is sufficiently large (i.e., > ~6 × 10(20) cm(-3)), which in turn modulates both the resonance wavelengths and the extinction ratio of the donut resonator simultaneously. For a modulator with the total footprint inclusive electrodes of ~8.6 µm(2), 50-nm-thick TiO(2), and 160-nm-thick Si core, FDTD simulation predicts that it has an insertion loss of ~2 dB, a modulation depth of ~8 dB at a voltage swing of ~6 V, a speed-of-response of ~35 GHz, and a switching energy of ~0.45 pJ/bit, and it is athermal around room temperature. The modulator's performances can be further improved by optimization of the coupling strength between the bus waveguide and the donut resonator.

Osteoarthritis year 2011 in review: clinical.

The purpose of this narrative year in review of clinical studies was to highlight a few publications related to obesity and weight loss, physical activity, and synovitis as well as disease modifying interventions that were published between September 2010 and September 2011. This year clinical research highlighted the extent to which obesity and osteoarthritis (OA) are impacting quality of life among adults in the United States and that reducing excessive body weight or becoming more physically active may be beneficial. In addition to weight loss and physical activity and synovitis, research over the past year has highlighted the diverse methods being pursued for structural modification interventions. In addition to chondroitin sulfate there were interesting preliminary findings that meniscal implants and joint distractions may modify OA progression.

Bone marrow lesions are associated with altered trabecular morphometry.

OBJECTIVE: Bone marrow lesions (BMLs) are a common magnetic resonance (MR) feature in patients with osteoarthritis, however their pathological basis remains poorly understood and has not been evaluated in vivo. Our aim was to evaluate the trabecular structure associated with the presence and size of BMLs present in the same regions of interest (ROI) using quantitative MR-based trabecular morphometry. DESIGN: 158 participants in the Osteoarthritis Initiative (OAI) were imaged with a coronal 3D fast imaging with steady state precession (FISP) sequence for trabecular morphometry in the same session as the OAI 3 T MR knee evaluation. The proximal medial tibial subchondral bone in the central weight-bearing ROI on these knee 3D FISP images were quantitatively evaluated for apparent bone volume fraction, trabecular number, spacing, and thickness. BMLs were also evaluated in the subchondral bone immediately adjacent to the articular cartilage. BML volume was also evaluated within the same trabecular morphometry ROI and semi-quantitatively classified as none, small, or large. Kruskal-Wallis test was used to determine if mean apparent bone volume fraction, trabecular number, spacing, or thickness differed by BML score. RESULTS: Compared to knees with ROIs containing no BMLs, knees with small or large BMLs had statistically higher apparent bone volume fraction (P < 0.01), trabecular number (P < 0.01), and thickness (P = 0.02), and lower trabecular spacing (P < 0.01). CONCLUSIONS: Compared to knees with ROIs containing no BMLs, knees with ROIs containing small or large BMLs had higher apparent bone volume fraction, trabecular number and thickness, but lower trabecular spacing. These findings may represent areas of locally increased bone remodeling or compression.

Cross-sectional DXA and MR measures of tibial periarticular bone associate with radiographic knee osteoarthritis severity.

OBJECTIVE: We evaluated the relationship of medial proximal tibial periarticular areal bone mineral density (paBMD) and trabecular morphometry and determined whether these bone measures differed across radiographic medial joint space narrowing (JSN) scores. METHODS: 482 participants of the Osteoarthritis Initiative (OAI) Bone Ancillary Study had knee dual X-ray absorptiometry (DXA) and trabecular bone 3T magnetic resonance imaging (MRI) exams assessed at the same visit. Medial proximal tibial paBMD was measured on DXA and apparent trabecular bone volume fraction (aBV/TV), thickness (aTb.Th), number (aTb.N), and spacing (aTb.Sp) were determined from MR images. Radiographs were assessed for medial JSN scores (0-3). We evaluated associations between medial paBMD and trabecular morphometry. Whisker plots with notches of these measures versus medial JSN scores were generated and presented. RESULTS: Mean age was 63.9 (9.2) years, BMI 29.6 (4.8) kg/m(2), and 53% were male. The Spearman correlation coefficients between DXA-measured medial paBMD and aBV/TV was 0.61 [95% confidence interval (CI) 0.55-0.66]; between paBMD and aTb.Th was 0.38 (95%CI 0.30-0.46); paBMD and aTb.N was 0.65 (95%CI 0.60-0.70); paBMD and aTb.Sp was -0.65 (95%CI -0.70 to -0.59). paBMD and the trabecular metrics were associated with medial JSN scores. CONCLUSION: The moderate associations between periarticular trabecular bone density and morphometry and their relationship with greater severity of knee OA support hypotheses of remodeling and/or microscopic compression fractures in the natural history of OA. Longitudinal studies are needed to assess whether knee DXA will be a predictor of OA progression. Further characterization of the periarticular bone in OA utilizing complementary imaging modalities will help clarify OA pathophysiology.

Components for silicon plasmonic nanocircuits based on horizontal Cu-SiO2-Si-SiO2-Cu nanoplasmonic waveguides.

We report systematic results on the development of horizontal Cu-SiO2-Si-SiO2-Cu nanoplasmonic waveguide components operating at 1550-nm telecom wavelengths, including straight waveguides, sharp 90° bends, power splitters, and Mach-Zehnder interferometers (MZIs). Owing to the relatively low loss for propagating (~0.3 dB/µm) and for 90° sharply bending (~0.73 dB/turn), various ultracompact power splitters and MZIs are experimentally realized on a silicon-on-insulator (SOI) platform using standard CMOS technology. The demonstrated splitters exhibit a relatively low excess loss and the MZIs exhibit good performance such as high extinction ratio of ~18 dB and low normalized insertion loss of ~1.7 dB. The experimental results of these devices agree well with those predicted from numerical simulations with suitable Cu permittivity data.