bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravesical Electro-Osmotic Administration of Mitomycin C
Authors: Di Stasi Savino M. , Verri Cristian , Celestino Francesco , De Carlo Francesco , Pagliarulo Vincenzo
Published: October 2016

Bladder cancer is very common and most cases are diagnosed as nonmuscle invasive disease, which is characterized by its propensity to recur and progress. Intravesical therapy is used to delay recurrence and progression, while cystectomy is reserved for patients who are refractory to transurethral resection and intravesical therapy. There is an increasing interest in methods to enhance the delivery of intravesical chemotherapeutic agents to improve efficacy. In vitro and in vivo studies demonstrated that electro-osmosis of mitomycin C (MMC) is more effective in delivering this drug into the urothelium, lamina propria, and superficial muscle layers of the bladder wall than is passive transport. Higher MMC tissue concentrations might have a clinical impact in the treatment of nonmuscle invasive bladder cancer (NMIBC). In randomized trials, intravesical electro-osmotic MMC was associated with superior response rate in high-risk NMIBC cancer, compared with passive diffusion MMC transport. New strategies such as intravesical Bacillus Calmette-Guerin (BCG) combined with electro-osmotic MMC as well as intravesical pre-operative electro-osmotic MMC provided promising results in terms of higher remission rates and longer remission times.

Device-assisted intravesical chemotherapy may be a useful ancillary procedure in the treatment of NMIBC. Its evaluation must be planned with respect to the technical functioning of equipment and their use for a clear purpose to avoid the financial and human costs associated with incorrect therapies.
Lipoma de cono medular
Authors: Guardado Ortiz Pablo Cesar , Urcuyo Napoleón
Published: October 2016

Acta Pediátrica Hondureña, Vol. 6, No. 1 Abril 2015 a Septiembre 2015: 422
Analysis of the light-extraction efficiency of SiC substrate-based flip-chip vertical light-emitting diodes with embedded photonic crystals
Authors: Liu Meng , Li Kang , Kong Fan-min , Zhao Jia , Zhao Shu-long , Meng Hao-tian
Published: October 2016

To improve the light-extraction efficiency (LEE) of flip-chip vertical light-emitting diodes (LEDs) grown on silicon carbide (SiC) substrate, embedded photonic crystals (PhCs) were alternatively introduced into the n-GaN layer of LEDs, since etching of the SiC substrate was very difficult. The finite-difference time-domain (FDTD) method was employed to investigate the combination effects of the micro-cavity and the embedded PhCs. The influences of the PhCs configurations on the LEE of LEDs were also examined to get an optimal structure. With the optimized parameters, about 20% enhancement of LEE was achieved comparing to planar SiC substrate-based flip-chip vertical LEDs. The LEE of conventional surface PhCs LEDs and double layer PhCs LEDs were also investigated for comparison. The results indicated that LEDs with carefully designed embedded PhCs could provide more LEE than surface PhCs LEDs. The structures proposed here offered scopes for the design of high-efficiency, high-power LEDs.
Basal conditions at the grounding zone of Whillans Ice Stream, West Antarctica, from ice‐penetrating radar
Authors: Christianson Knut , Jacobel Robert W. , Horgan Huw J. , Alley Richard B. , Anandakrishnan Sridhar , Holland David M. , DallaSanta Kevin J.
Published: October 2016

We present a comprehensive ice‐penetrating radar survey of a subglacial embayment and adjacent peninsula along the grounding zone of Whillans Ice Stream, West Antarctica. Through basal waveform and reflectivity analysis, we identify four distinct basal interfaces: (1) an ice‐water‐saturated till interface inland of grounding; (2) a complex interface in the grounding zone with variations in reflectivity and waveforms caused by reflections from fluting, sediment deposits, and crevasses; (3) an interface of anomalously low‐reflectivity downstream of grounding in unambiguously floating areas of the embayment due to basal roughness and entrained debris; and (4) a high‐reflectivity ice‐seawater interface that occurs immediately seaward of grounding at the subglacial peninsula and several kilometers seaward of grounding in the embayment, occurring after basal debris and grounding zone flutes have melted off the ice bottom. Sediment deposition via basal debris melt‐out occurs in both locations. The higher basal melt rate at the peninsula contributes to greater grounding line stability by enabling faster construction of a stabilizing sediment wedge. In the embayment, the low slopes of the ice bottom and bed prevent development of a strong thermohaline circulation leading to a lower basal melt rate and less rapid sediment deposition. Thus, grounding lines in subglacial embayments are more likely to lack stabilizing sediment deposits and are more prone to external forcing, whether from the ocean, the subglacial water system, or large‐scale ice dynamics. Our conclusions indicate that subglacial peninsulas and embayments should be treated differently in ice sheet‐ocean models if these models are to accurately simulate grounding line response to external forcing.
Impacts of second‐generation biofuel feedstock production in the central U.S. on the hydrologic cycle and global warming mitigation potential
Authors: Harding K. J. , Twine T. E. , VanLoocke A. , Bagley J. E. , Hill J.
Published: October 2016

Biofuel feedstocks provide a renewable energy source that can reduce fossil fuel emissions; however, if produced on a large scale they can also impact local to regional water and carbon budgets. Simulation results for 2005–2014 from a regional weather model adapted to simulate the growth of two perennial grass biofuel feedstocks suggest that replacing at least half the current annual cropland with these grasses would increase water use efficiency and drive greater rainfall downwind of perturbed grid cells, but increased evapotranspiration (ET) might switch the Mississippi River basin from having a net warm‐season surplus of water (precipitation minus ET) to a net deficit. While this scenario reduces land required for biofuel feedstock production relative to current use for maize grain ethanol production, it only offsets approximately one decade of projected anthropogenic warming and increased water vapor results in greater atmospheric heat content.
A theoretical model for fluvial channel response time during time‐dependent climatic and tectonic forcing and its inverse applications
Authors: Goren Liran
Published: October 2016

The fluvial response time dictates the duration of fluvial channel adjustment in response to changing climatic and tectonic conditions. However, when these conditions vary continuously, the channel cannot equilibrate and the response time is not well defined. Here I develop an analytical solution to the linear stream power model of fluvial incision that predicts the channel topography as a function of time‐dependent climatic and tectonic conditions. From this solution, a general definition of the fluvial response time emerges: the duration over which the tectonic history needs to be known to evaluate channel topography. This new definition is used in linear inversion schemes for inferring climatic or tectonic histories from river long profiles. The analytic solution further reveals that high‐frequency climatic oscillations, such as Milankovitch cycles, are not expected to leave significant fingerprints on the long profiles of fluvially incised detachment‐limited rivers.
ENSO controls interannual fire activity in southeast Australia
Authors: Mariani M. , Fletcher M.‐S. , Holz A. , Nyman P.
Published: October 2016

El Niño–Southern Oscillation (ENSO) is the main mode controlling the variability in the ocean‐atmosphere system in the South Pacific. While the ENSO influence on rainfall regimes in the South Pacific is well documented, its role in driving spatiotemporal trends in fire activity in this region has not been rigorously investigated. This is particularly the case for the highly flammable and densely populated southeast Australian sector, where ENSO is a major control over climatic variability. Here we conduct the first region‐wide analysis of how ENSO controls fire activity in southeast Australia. We identify a significant relationship between ENSO and both fire frequency and area burnt. Critically, wavelet analyses reveal that despite substantial temporal variability in the ENSO system, ENSO exerts a persistent and significant influence on southeast Australian fire activity. Our analysis has direct application for developing robust predictive capacity for the increasingly important efforts at fire management.
Magnitude‐based discrimination of man‐made seismic events from naturally occurring earthquakes in Utah, USA
Authors: Koper Keith D. , Pechmann James C. , Burlacu Relu , Pankow Kristine L. , Stein Jared , Hale J. Mark , Roberson Paul , McCarter Michael K.
Published: October 2016

We investigate using the difference between local (ML) and coda/duration (MC) magnitude to discriminate man‐made seismic events from naturally occurring tectonic earthquakes in and around Utah. For 6846 well‐located earthquakes in the Utah region, we find that ML‐MC is on average 0.44 magnitude units smaller for mining‐induced seismicity (MIS) than for tectonic seismicity (TS). Our interpretation of this observation is that MIS occurs within near‐surface low‐velocity layers that act as a waveguide and preferentially increase coda duration relative to peak amplitude, while the vast majority of TS occurs beneath the near‐surface waveguide. A second data set of 3723 confirmed or probable explosions in the Utah region also has significantly lower ML‐MC values than TS, likely for the same reason as the MIS. These observations suggest that ML‐MC is useful as a depth indicator and could discriminate small explosions and mining‐induced earthquakes from deeper, naturally occurring earthquakes at local‐to‐regional distances.
Olivine settling in cosmic spherules during atmospheric deceleration: An indicator of the orbital eccentricity of interplanetary dust
Authors: Genge Matthew J. , Suttle Martin , Van Ginneken Matthias
Published: October 2016

A new type of cosmic spherule is reported with textures suggesting settling of olivine during atmospheric deceleration. Numerical simulations of entry heating reveal that relict forsterite, which survives melting, can settle over the 1–2 s of flight at high entry angles and entry velocities up to 16 km s−1. Enhanced crystallization of phenocrysts by heterogeneous nucleation on accumulated relict forsterites is the most likely origin of the observed cumulate textures in cosmic spherules. Such textures in cosmic spherules reveal interplanetary dust with higher encounter velocity with the Earth that correspond to orbital eccentricities >0.3. The relative abundance of cumulate spherules suggests that 14% of ordinary chondrite‐related, S(IV)‐type asteroid dust over the last 800 kyr had relatively high orbital eccentricity owing to secular and planetary perturbations. The textures of cosmic spherules collected from sediments can therefore be used to trace dust orbital variations with time, which may influence terrestrial climate.
Aerosol optical depth distribution in extratropical cyclones over the Northern Hemisphere oceans
Authors: Naud Catherine M. , Posselt Derek J. , van den Heever Susan C.
Published: October 2016

Using Moderate Resolution Imaging Spectroradiometer and an extratropical cyclone database, the climatological distribution of aerosol optical depth (AOD) in extratropical cyclones is explored based solely on observations. Cyclone‐centered composites of aerosol optical depth are constructed for the Northern Hemisphere midlatitude ocean regions, and their seasonal variations are examined. These composites are found to be qualitatively stable when the impact of clouds and surface insolation or brightness is tested. The larger AODs occur in spring and summer and are preferentially found in the warm frontal and in the postcold frontal regions in all seasons. The fine mode aerosols dominate the cold sector AODs, but the coarse mode aerosols display large AODs in the warm sector. These differences between the aerosol modes are related to the varying source regions of the aerosols and could potentially have different impacts on cloud and precipitation within the cyclones.
Surface creep on the North Anatolian Fault at Ismetpasa, Turkey, 1944–2016
Authors: Bilham Roger , Ozener H. , Mencin D. , Dogru A. , Ergintav S. , Cakir Z. , Aytun A. , Aktug B. , Yilmaz O. , Johnson W. , Mattioli G.
Published: October 2016

We reevaluate the 72 year history of surface slip on the North Anatolian Fault at Ismetpasa since the Mw = 7.4 1944 Bolu/Gerede earthquake. A revised analysis of published observations suggests that days after the earthquake the fault had been offset by 3.7 m and 6 years later by an additional 0.74 m. Creep was first recognized on the fault in 1969 as a 0.13 m offset of a wall constructed in 1957 that now (2016) has been offset by 0.52 m. A carbon rod creep meter operated across the fault in the past 2 years confirms results from an invar wire creep meter operated 1982–1991 that surface slip is episodic. Months of fault inactivity are interrupted by slow slip (≤10 µm/d) or multiple creep events with cumulative amplitudes of 2–10 mm, durations of several weeks, and with slip rates briefly exceeding >2.5 mm/h. Creep events accommodate 80% of the surface slip and individually release ≈ 10−6 shear strain on the flanks of the uppermost 3–7 km of the fault. GPS and interferometric synthetic aperture radar methods yield a current fault slip rate of 7.6 ± 1 mm/yr suggesting that creep meters incompletely sample the full width of the surface shear zone. The slip rate has slowed from >10 mm/yr in 1969 to 6.1 mm/yr at present, 4.65 mm/yr of which appears to be due to steady interseismic creep driven by plate boundary stressing rates. We calculate that a further 1 m of aseismic surface slip will precede the next major earthquake on the fault assuming an ≈ 260 year main shock recurrence interval on this segment.
Properties of hail storms over China and the United States from the Tropical Rainfall Measuring Mission
Authors: Ni Xiang , Liu Chuntao , Zhang Qinghong , Cecil Daniel J.
Published: October 2016

A 16 year record of hail reports over the south U.S. and from weather stations in China are collocated with precipitation features (PFs) derived from the Tropical Rainfall Measuring Mission (TRMM) radar and passive microwave observations. Differences in the way hail is reported in the two nations make it difficult to draw meaningful conclusions about storm frequency. But taking the two together yields a wide spectrum of hail sizes, suitable for comparing with remote sensing measurements. While U.S. hail reports are dominated by cases with hail size greater than 19 mm, hail reports in China mostly include diameters of 1–10 mm and mostly occur over the Tibetan Plateau. The fraction of PFs collocated with hail reports (hail PFs) reaches 3% in the plains of the U.S. In China, the fraction is higher in high elevation regions than low elevation regions. Hail PFs (as reported in the U.S.) show lower brightness temperatures, higher lightning flash rates, stronger maximum reflectivity, and higher echo tops than those with smaller hail, as reported in China. The average near surface maximum reflectivity of hail PFs at high elevations (≥2000 m) in China is about 5 dB smaller than those at low elevations. Larger hail is reported with PFs having stronger maximum reflectivity above 6 km, though the median of maximum reflectivity values at levels below 5 km is similar among the storms with large and small hail sizes.
Chondrules: The canonical and noncanonical views
Authors: Connolly Harold C. , Jones Rhian H.
Published: October 2016

Millimeter‐scale rock particles called chondrules are the principal components of the most common meteorites, chondrites. Hence, chondrules were arguably the most abundant components of the early solar system at the time of planetesimal accretion. Despite their fundamental importance, the existence of chondrules would not be predicted from current observations and models of young planetary systems. There are many different models for chondrule formation, but no single model satisfies the many constraints determined from their mineralogical and chemical properties and from chondrule analog experiments. Significant recent progress has shown that several models can satisfy first‐order constraints and successfully reproduce chondrule thermal histories. However, second‐ and third‐order constraints such as chondrule size ranges, open system behavior, oxidation states, reheating, and chemical diversity have not generally been addressed. Chondrule formation models include those based on processes that are known to occur in protoplanetary disk environments, including interactions with the early active Sun, impacts and collisions between planetary bodies, and radiative heating. Other models for chondrule heating mechanisms are based on hypothetical processes that are possible but have not been observed, like shock waves, planetesimal bow shocks, and lightning. We examine the evidence for the canonical view of chondrule formation, in which chondrules were free‐floating particles in the protoplanetary disk, and the noncanonical view, in which chondrules were the by‐products of planetesimal formation. The fundamental difference between these approaches has a bearing on the importance of chondrules during planet formation and the relevance of chondrules to interpreting the evolution of protoplanetary disks and planetary systems.
Impact of biomass burning on soil microorganisms and plant metabolites: A view from molecular distributions of atmospheric hydroxy fatty acids over Mount Tai
Authors: Tyagi Poonam , Kawamura Kimitaka , Fu Pingqing , Bikkina Srinivas , Kanaya Yugo , Wang Zifa
Published: October 2016

Biomass burning events (BBEs) in the North China Plain is one of the principal sources of airborne pollutants in China and also for the neighboring countries. To examine the impact of BBEs on soil bacteria and other higher plant metabolites, their tracer compounds, hydroxy fatty acids (FAs), were measured in the bulk particulate matter (total suspended particles (TSP)) over Mount Tai during the period of wheat residue burning in June 2006. Higher inputs of epicuticular waxes and soil microorganisms during high BBEs (H; 6–14 and 27 June) relative to low BBEs (L; 15–26 and 28 June) were characterized by increased concentrations of homologous series of α‐(C9–C32), β‐(C9–C32), and ω‐(C12–C28) hydroxy FAs in TSP samples. However, their relative abundances were not significantly different between H‐BBEs and L‐BBEs, suggesting their common source/transport pathways. We also found higher concentrations of trehalose and mannitol (tracers of soil microbes), and levoglucosan (tracer of biomass combustion) during H‐BBEs than L‐BBEs. These results are consistent with hydroxy FAs, suggesting that they are associated with biomass combustion processes of agricultural wastes as well as re‐suspension of mineral dust and plant pathogens. In addition, enhanced concentrations of endotoxin and mass loading of Gram‐negative bacteria during H‐BBEs (117 endotoxin units (EU) m−3 and 390 ng m−3, respectively) were noteworthy as compared to those in L‐BBEs (22.5 EU m−3 and 75 ng m−3, respectively). Back trajectory analysis and fire spots together with temporal variations of hydroxy FAs revealed an impact of biomass burning on emissions and atmospheric transport of bacteria and plant metabolites.
Microbial lipid signatures and substrate potential of organic matter in permafrost deposits: Implications for future greenhouse gas production
Authors: Stapel J. G. , Schirrmeister L. , Overduin P. P. , Wetterich S. , Strauss J. , Horsfield B. , Mangelsdorf K.
Published: October 2016

A terrestrial permafrost core from Buor Khaya in northern Siberia comprising deposits of Late Pleistocene to Early Holocene age has been investigated to characterize living and past microbial communities with respect to modern and paleoclimate environmental conditions and to evaluate the potential of the organic matter (OM) for greenhouse gas generation. Microbial life markers—intact phospholipids and phospholipid fatty acids—are found throughout the entire core and indicate the presence of living microorganisms also in older permafrost deposits. Biomarkers for past microbial communities (branched and isoprenoid glycerol dialkyl glycerol tetraether as well as archaeol) reveal links between increased past microbial activity and intervals of high OM accumulation accompanied by increased OM quality presumably caused by local periods of moister and warmer environmental conditions. Concentrations of acetate as an excellent substrate for methanogenesis are used to assess the OM quality with respect to microbial degradability for greenhouse gas production. For this purpose two acetate pools are determined: the pore water acetate and OM bound acetate. Both depth profiles reveal similarities to the OM content and quality indicating a link between the amount of the stored OM and the potential to provide substrates for microbial greenhouse gas production. The data suggest that OM stored in the permafrost deposits is not much different in terms of OM quality than the fresh surface organic material. Considering the expected increase of permafrost thaw due to climate warming, this implies a potentially strong impact on greenhouse gas generation from permafrost areas in future with positive feedback on climate variation.
Human promyelocytic leukemia protein is targeted to distinct subnuclear domains in plant nuclei and colocalizes with nucleolar constituents in a SUMO‐dependent manner
Authors: Lamm Christian E. , Scherer Myriam , Reuter Nina , Amin Bushra , Stamminger Thomas , Sonnewald Uwe
Published: October 2016

Eukaryotic nuclei are subdivided into subnuclear structures. Among the most prominent of these structures are the nucleolus and the PML nuclear bodies (PML‐NBs). PML‐NBs are spherical multiprotein aggregates of varying size localized in the interchromosomal area. PML‐NB formation is dependent on the presence of the promyelocytic leukemia protein (PML) as well as on post‐translational modification of core components by covalent attachment of the small ubiquitin‐like modifier (SUMO). So far, PML‐NBs as well as PML have been described in mammalian cells only, whereas no orthologs are known in the plant kingdom. In order to investigate conserved mechanisms in PML targeting, we expressed human PML (hPML) fused to the GFP in Nicotiana benthamiana. Using confocal laser scanning microscopy and coimmunoprecipitation followed by mass spectrometric analysis, we found the fusion protein in association with nucleolar constituents. Importantly, mutants of hPML, which are no longer SUMOylated, showed altered localizations, implying SUMO‐dependent targeting of hPML in plants as has previously been shown for mammalian cells. Interestingly, in the presence of proteasome inhibitors, hPML could also be found in the nucleolus of mammalian cells suggesting conserved targeting mechanisms of PML across kingdoms. Finally, Solanum tuberosum COP1, a proposed PML‐like protein from plants, was fused to the red fluorescent protein (RFP) and coexpressed with hPML::eGFP. Microscopic analysis confirmed the localization of COP1::RFP in nuclear speckles. However, hPML::eGFP did not colocalize with COP1::RFP. Hence, we conclude that plants do not possess specialized PML‐NBs, but that their functions may be covered by other subnuclear structures like the nucleolus.

Database Proteomics data have been deposited to the ProteomeXchange Consortium with the identifier PXD004254.
Association of Beta‐Blocker Use With Less Prevalent Joint Pain and Lower Opioid Requirement in People With Osteoarthritis
Authors: Valdes Ana M. , Abhishek Abhishek , Muir Kenneth , Zhang Weiya , Maciewicz Rose A. , Doherty Michael
Published: October 2016

Objective

Recent findings suggest that β‐adrenergic blockers have antinociceptive properties. The aim of this study was to compare levels of large‐joint pain between those taking adrenergic blockers and those taking other antihypertensive medications.

Methods

Data from the Genetics of Osteoarthritis and Lifestyle (GOAL) study, a secondary‐care cohort of osteoarthritis (OA) patients, were used. Joint pain was assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores in 873 individuals with symptomatic hip and/or knee OA and hypertension, who were taking ≥1 prescription antihypertensive medications. The association between adrenergic blocker prescription and at least moderate joint pain (WOMAC score <75) and use of prescription analgesics was examined using binary logistic regression. Analyses were adjusted for age, sex, body mass index, knee or hip OA, history of joint replacement (at other joints), anxiety, and depression.

Results

The use of β‐adrenergic blockers was associated with lower WOMAC pain scores and with a lower prevalence of joint pain after adjustment for demographic variables and comorbidity (adjusted odds ratio [ORadj] for pain 0.68 [95% confidence interval (95% CI) 0.51, 0.92]; P < 0.011). No associations with pain were observed with use of alpha‐blockers (ORadj for pain 0.94 [95% CI 0.55, 1.58]) or with any other class of antihypertensive medications. Prescription of beta‐blockers was also associated negatively with opioid use (ORadj for opioids 0.73 [95% CI 0.54, 0.98]; P < 0.037) and with the use of prescription analgesics in general (ORadj for analgesics 0.74 [95% CI 0.56, 0.94]; P < 0.032).

Conclusion

The use of beta‐blockers is associated with less joint pain and a lower use of opioids and other analgesics in individuals with symptomatic large‐joint OA. This observation needs to be confirmed by other studies.
Incidence and Management of Cardiovascular Risk Factors in Psoriatic Arthritis and Rheumatoid Arthritis: A Population‐Based Study
Authors: Jafri Kashif , Bartels Christie M. , Shin Daniel , Gelfand Joel M. , Ogdie Alexis
Published: October 2016

Objective

To examine the prevalence and incidence of cardiovascular (CV) risk factors, including hypertension, hyperlipidemia, diabetes mellitus (DM), and obesity among patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) compared to the general population, and to examine the treatment of incident CV risk factors in PsA and RA compared to controls.

Methods

A cohort study was conducted within The Health Improvement Network, a medical record database in the UK, using data from 1994 to 2014. Patients ages 18–89 years with PsA or RA were matched to controls on practice and start date. The prevalence and incidence of CV risk factors identified by diagnostic codes were calculated. Cox proportional hazards models were used to examine the relative incidence of these CV risk factors. Finally, pharmacologic therapies for incident CV risk factors were examined.

Results

Study subjects included patients with PsA (n = 12,548), RA (n = 53,215), and controls (n = 389,269). The prevalence of all CV risk factors was significantly elevated in PsA. Only the prevalence of DM and obesity was increased in RA. Incidence of hypertension, hyperlipidemia, and DM was elevated in PsA and RA. Receipt of therapy within 1 year following incident diagnosis of CV risk factors was not substantially different between the groups; approximately 85%, 65%, and 45% of patients received prescriptions for hypertension, hyperlipidemia, and DM, respectively.

Conclusion

Patients with PsA have an increased prevalence of CV risk factors, and both patients with PsA and patients with RA have increased incidence of a new diagnosis of CV risk factors. Pharmacologic treatment of CV risk factors in patients with PsA and RA was similar to controls in the UK.
Personalized Physical Therapy Versus Usual Care for Patients With Systemic Sclerosis: A Randomized Controlled Trial
Authors: Rannou François , Boutron Isabelle , Mouthon Luc , Sanchez Katherine , Tiffreau Vincent , Hachulla Eric , Thoumie Philipe , Cabane Jean , Chatelus Emmanuel , Sibilia Jean , Roren Alexandra , Berezne Alice , Baron Gabriel , Porcher Raphael , Guillevin Loic , Ravaud Philippe , Poiraudeau Serge
Published: October 2016

Objective

To compare a physical therapy program to usual care of systemic sclerosis (SSc) patients on disability.

Methods

A 12‐month followup, parallel‐group randomized controlled trial involving a modified Zelen design was conducted in 4 tertiary‐care hospitals. Patients were enrolled if they had a disability rating ≥0.5 on the Health Assessment Questionnaire disability index (HAQ DI) or symptoms of decreased mouth opening or limited range of motion of at least 1 joint. The experimental intervention (n = 112, of which 110 were analyzed) was a 1‐month personalized supervised physical therapy program provided by trained care providers followed by home sessions. The comparator (n = 108, and all 108 were analyzed) was usual care that could include ambulatory physical therapy. The primary outcome was the HAQ DI score.

Results

There was no statistically significant difference in disability at 12 months (HAQ DI score between‐group difference −0.01 [95% confidence interval (95% CI) −0.15, 0.13]; P = 0.86). Disability was reduced at 1 month for patients in the physical therapy group (HAQ DI between‐group difference −0.14 [95% CI −0.24, −0.03]; P = 0.01); at 6 months the HAQ DI score between‐group difference was −0.12 (95% CI −0.23, 0.01); P = 0.054. There was a statistically significant difference for hand mobility and function, and for pain, at 1 month. Microstomia was lower in the physical therapy group at 1, 6, and 12 months (between‐group difference at 12 months 1.62 [95% CI 0.32, 2.93]; P = 0.01). No differences in adverse effects were observed.

Conclusion

A personalized physical therapy program did not reduce disability at 12 months but had short‐term benefits for patients with SSc.
Standards of Comparison and Discordance in Rheumatoid Arthritis Global Assessments Between Patients and Clinicians
Authors: Ward Michael M. , Guthrie Lori C. , Alba Maria I.
Published: October 2016

Objective

Patient‐physician discordance in health status ratings may arise because patients use temporal comparisons (comparing their current status with their previous status), while clinicians use social comparisons (comparing this patient's status to that of other patients, or to the full range of disease severity possible) to guide their assessments. We compared discordance between patients with rheumatoid arthritis (RA) and clinicians, using either the conventional patient global assessment (PGA) or a rating scale with 5 anchors describing different health states. We hypothesized that discordance would be smaller with the rating scale because clinicians likely used similar social comparisons when making global assessments.

Methods

We prospectively studied 206 patients with active RA and assessed the PGA (range 0–100), rating scale (range 0–100), and evaluator global assessment (EGA; range 0–100) on each of 2 visits (total visits = 401). We compared the PGA/EGA discordance and the rating scale/EGA discordance at each visit.

Results

The mean ± SD PGA/EGA discordance was 8.5 ± 22.4, and the mean ± SD rating scale/EGA discordance was 2.3 ± 24.0. The intraclass correlation, measuring agreement, was higher between the rating scale and EGA than between the PGA and EGA (0.39 versus 0.31). Agreement was larger at low levels of RA activity on both pairs of measures.

Conclusion

Discordance between patients’ global assessments and evaluators’ global assessments was smaller when patients used a social standard of comparison than when they marked the PGA, suggesting that differences in standards of comparison contribute to patient‐clinician discordance when the PGA is used.
Relationship Between Attitudes and Beliefs and Physical Activity in Older Adults With Knee Pain: Secondary Analysis of a Randomized Controlled Trial
Authors: Quicke Jonathan G. , Foster Nadine E. , Ogollah Reuben O. , Croft Peter R. , Holden Melanie A.
Published: October 2016

Objective

To investigate how attitudes and beliefs about exercise relate to physical activity behavior in older adults with knee pain attributable to osteoarthritis (OA).

Methods

We conducted secondary data analyses of a randomized controlled trial of exercise interventions (ISRCTN: 93634563). Participants were adults ≥45 years old with knee pain attributable to OA (n = 514). Crude and adjusted cross‐sectional and longitudinal associations between baseline Self‐Efficacy for Exercise (SEE), Positive Outcome Expectations for Exercise (POEE), Negative Outcome Expectations for Exercise scores, and physical activity level, at baseline, 3 months, and 6 months (measured by self‐report using the Physical Activity Scale for the Elderly [PASE]), and important increases in physical activity level (from baseline to 6‐month followup) were investigated using multiple linear and logistic regression.

Results

Cross‐sectional associations were found between SEE and PASE scores (β = 4.14 [95% confidence interval (95% CI) 0.26, 8.03]) and POEE and PASE scores (β = 16.71 [95% CI 1.87, 31.55]), adjusted for sociodemographic and clinical covariates. Longitudinal associations were found between baseline SEE and PASE scores at 3 months (β = 4.95 [95% CI 1.02, 8.87]) and 6 months β = 3.71 (0.26, 7.16), and baseline POEE and PASE at 3 months (β = 34.55 [95% CI 20.13, 48.97]) and 6 months (β = 25.74 [95% CI 11.99, 39.49]), adjusted for baseline PASE score and intervention arm. However, no significant associations with important increases in physical activity level were found.

Conclusion

Greater exercise self‐efficacy and more positive exercise outcome expectations were associated with higher current and future physical activity levels. These may be targets for interventions aimed at increasing physical activity.
Defining Low Disease Activity in Systemic Lupus Erythematosus
Authors: Polachek Ari , Gladman Dafna D. , Su Jiandong , Urowitz Murray B.
Published: October 2016

Objective

To define and identify a group of systemic lupus erythematosus patients with low disease activity (LDA) and to examine whether LDA is similar to patients in remission and different from a high disease activity group (HDA) in short‐term outcomes.

Methods

The LDA group was defined as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) <3, including only 1 clinical manifestation of rash, alopecia, mucosal ulcers, pleurisy, pericarditis, fever, thrombocytopenia, or leukopenia. The patients could be taking antimalarials. Remission was defined as no clinical manifestation from taking antimalarials alone, and the HDA group was defined as SLEDAI‐2K >6. The time frame for inclusion in each group was at least 1 year.

Results

Of 620 patients with active disease who were seen between 1970 and 2015, 80 patients (12.9%) fulfilled the criteria for LDA, 191 (30.8%) for remission, and 349 (56.3%) for HDA. The LDA patients with and without positive serology results were similar at baseline and with prior disease characteristics. After 2 years of followup, the LDA and remission groups were similar in their adjusted mean SLEDAI‐2K score, organ involvement, The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score, mortality, and therapies. After 2 and 4 years of followup, the HDA group had a higher adjusted mean SLEDAI‐2K score, more major organ involvement, a higher SDI score, higher mortality, and more therapy compared to the combined LDA/remission groups.

Conclusion

LDA and remission groups had similar short‐term outcomes, and both had better outcomes and prognosis than the HDA group. LDA may be used as an outcome measure in therapeutic trials or in treat‐to‐target regimens.
Do Short and Sustained Periods of American College of Rheumatology/European League Against Rheumatism Remission Predict Functional and Radiographic Outcome in Early Rheumatoid Arthritis Patients With Low Overall Damage Progression?
Authors: Konijn Nicole P. C. , van Tuyl Lilian H. D. , Boers Maarten , den Uyl Debby , ter Wee Marieke M. , Kerstens Pit , Voskuyl Alexandre E. , van Schaardenburg Dirkjan , Nurmohamed Michael T. , Lems Willem F.
Published: October 2016

Objective

To investigate whether remission at single and consecutive visits predicts good outcome in early rheumatoid arthritis (RA).

Methods

The presence of remission according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) and other criteria (Boolean clinical, Clinical Disease Activity Index, Disease Activity Score [DAS], DAS in 28 joints, and Routine Assessment of Patient Index Data 3) was assessed in early RA patients during the first year of the Combination Therapy for Rheumatoid Arthritis light trial. Likelihood ratios were used to assess whether meeting the remission criteria at single visits (13, 26, 39, or 52 weeks) and consecutive visits (13 and 26, 26 and 39, or 39 and 52 weeks) predicted good outcome in the second year (52–104 weeks). Good outcome was defined for function (Health Assessment Questionnaire score consistently ≤0.5 and no deterioration), radiographic damage progression (no deterioration in Sharp/van der Heijde scores), and both (“overall good outcome”).

Results

Of the original 164 trial patients, 144 had evaluable data. In the second year, good functional outcome was observed in 35%, good radiographic outcome in 79%, and both in 28% of the patients. Almost all criteria predicted good functional and good overall outcome, at both single and consecutive visits; only single DAS remission did not significantly predict good overall outcome (P = 0.07). Sustained remission periods resulted in higher likelihood ratios than remission at single visits. None of the criteria predicted good radiographic outcome.

Conclusion

Early RA patients who reached remission according to ACR/EULAR and other criteria during short or sustained periods were likely to retain good physical function in the subsequent months. Sustained remission periods were a stronger predictor than remission at single visits. However, in the setting of low overall damage progression, (sustained) remission was not predictive of good radiographic outcome.
Partially methylated alleles, microdeletion, and tissue mosaicism in a fragile X male with tremor and ataxia at 30 years of age: A case report
Authors: Hwang Yun Tae , Aliaga Solange Mabel , Arpone Marta , Francis David , Li Xin , Chong Belinda , Slater Howard Robert , Rogers Carolyn , Bretherton Lesley , Hunter Matthew , Heard Robert , Godler David Eugeny
Published: October 2016

CGG repeat expansion >200 within FMR1, termed full mutation (FM), has been associated with promoter methylation, consequent silencing of gene expression and fragile X syndrome (FXS)—a common cause of intellectual disability and co‐morbid autism. Unmethylated premutation (55–199 repeats) and FM alleles have been associated with fragile X related tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder. Here we present a 33‐year‐old male with FXS, with white matter changes and progressive deterioration in gait with cerebellar signs consistent with probable FXTAS; there was no evidence of any other cerebellar pathology. We show that he has tissue mosaicism in blood, saliva, and buccal samples for the size and methylation of his expanded alleles and a de novo, unmethylated microdeletion. This microdeletion involves a ∼80 bp sequence in the FMR1 promoter as well as complete loss of the CGG repeat in a proportion of cells. Despite FMR1 mRNA levels in blood within the normal range, the methylation and CGG sizing results are consistent with the diagnosis of concurrent FXS and probable FXTAS. The demonstrated presence of unmethylated FM alleles would explain the manifestation of milder than expected cognitive and behavioral impairments and early onset of cerebellar ataxia. Our case suggests that individuals with FXS, who manifest symptoms of FXTAS, may benefit from more detailed laboratory testing. © 2016 Wiley Periodicals, Inc.
Incidence and impact of subclinical epileptiform activity in Alzheimer's disease
Authors: Vossel Keith A. , Ranasinghe Kamalini G. , Beagle Alexander J. , Mizuiri Danielle , Honma Susanne M. , Dowling Anne F. , Darwish Sonja M. , Van Berlo Victoria , Barnes Deborah E. , Mantle Mary , Karydas Anna M. , Coppola Giovanni , Roberson Erik D. , Miller Bruce L. , Garcia Paul A. , Kirsch Heidi E. , Mucke Lennart , Nagarajan Srikantan S.
Published: October 2016

Objective

Seizures are more frequent in patients with Alzheimer's disease (AD) and can hasten cognitive decline. However, the incidence of subclinical epileptiform activity in AD and its consequences are unknown. Motivated by results from animal studies, we hypothesized higher than expected rates of subclinical epileptiform activity in AD with deleterious effects on cognition.

Methods

We prospectively enrolled 33 patients (mean age, 62 years) who met criteria for AD, but had no history of seizures, and 19 age‐matched, cognitively normal controls. Subclinical epileptiform activity was assessed, blinded to diagnosis, by overnight long‐term video‐electroencephalography (EEG) and a 1‐hour resting magnetoencephalography exam with simultaneous EEG. Patients also had comprehensive clinical and cognitive evaluations, assessed longitudinally over an average period of 3.3 years.

Results

Subclinical epileptiform activity was detected in 42.4% of AD patients and 10.5% of controls (p = 0.02). At the time of monitoring, AD patients with epileptiform activity did not differ clinically from those without such activity. However, patients with subclinical epileptiform activity showed faster declines in global cognition, determined by the Mini–Mental State Examination (3.9 points/year in patients with epileptiform activity vs 1.6 points/year in patients without; p = 0.006), and in executive function (p = 0.01).

Interpretation

Extended monitoring detects subclinical epileptiform activity in a substantial proportion of patients with AD. Patients with this indicator of network hyperexcitability are at risk for accelerated cognitive decline and might benefit from antiepileptic therapies. These data call for more sensitive and comprehensive neurophysiological assessments in AD patient evaluations and impending clinical trials. Ann Neurol 2016;80:858–870
Cam Deformity and Acetabular Dysplasia as Risk Factors for Hip Osteoarthritis
Authors: Saberi Hosnijeh Fatemeh , Zuiderwijk Maria E. , Versteeg Mathijs , Smeele Hieronymus T. W. , Hofman Albert , Uitterlinden André G. , Agricola Rintje , Oei Edwin H. G. , Waarsing Jan H. , Bierma‐Zeinstra Sita M. , van Meurs Joyce B. J.
Published: October 2016

Objective

Cam deformity and acetabular dysplasia have been recognized as relevant risk factors for hip osteoarthritis (OA) in a few prospective studies with limited sample sizes. To date, however, no evidence is available from prospective studies regarding whether the magnitude of these associations differs according to sex, body mass index (BMI), and age.

Methods

Participants in the Rotterdam Study cohort including men and women ages 55 years or older without OA at baseline (n = 4,438) and a mean follow‐up of 9.2 years were included in the study. Incident radiographic OA was defined as a Kellgren/Lawrence grade of ≥2 or a total hip replacement at follow‐up. Alpha and center‐edge angles were measured to determine the presence of cam deformity and acetabular dysplasia/pincer deformity, respectively. Odds ratios (ORs) were calculated to assess the associations between both deformities and the development of OA.

Results

Subjects with cam deformity (OR 2.11, 95% confidence interval [95% CI] 1.55–2.87) and those with acetabular dysplasia (OR 2.19, 95% CI 1.50–3.21) had a 2‐fold increased risk of developing OA compared with subjects without deformity, while pincer deformity did not increase the risk of OA. Stratification analyses showed that the associations of cam deformity and acetabular dysplasia with OA were driven by younger individuals, whereas BMI did not influence the associations. Female sex appears to modify the risk of hip OA related to acetabular dysplasia.

Conclusion

Individuals with cam deformity and those with acetabular dysplasia are predisposed to OA; these associations were independent of other well‐known risk factors. Interestingly, both deformities predisposed to OA only in relatively young individuals. Therefore, early identification of these conditions is important.
Anti–Interleukin‐6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis–Associated Uveitis Refractory to Anti–Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty‐Five Patients
Authors: Calvo‐Río Vanesa , Santos‐Gómez Montserrat , Calvo Inmaculada , González‐Fernández M. Isabel , López‐Montesinos Berta , Mesquida Marina , Adán Alfredo , Hernández María Victoria , Maíz Olga , Atanes Antonio , Bravo Beatriz , Modesto Consuelo , Díaz‐Cordovés Gisela , Palmou‐Fontana Natalia , Loricera Javier , González‐Vela M. C. , Demetrio‐Pablo Rosalía , Hernández J. L. , González‐Gay Miguel A. , Blanco Ricardo
Published: October 2016

Objective

To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)–associated uveitis.

Methods

We conducted a multicenter study of patients with JIA‐associated uveitis that was refractory to conventional immunosuppressive drugs and anti–tumor necrosis factor (anti‐TNF) agents.

Results

We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1–5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best‐corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow‐up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient.

Conclusion

TCZ appears to be a useful therapy for severe refractory JIA‐associated uveitis.