4,133 research outputs found
Tofacitinib in Patients With Psoriatic Arthritis and Metabolic Syndrome: A Post hoc Analysis of Phase 3 Studies
Objective:
Metabolic syndrome (MetS) is a cluster of concurrent risk factors for cardiovascular disease and type 2 diabetes. This post hoc analysis explored key efficacy and safety endpoints in patients with psoriatic arthritis (PsA) and MetS treated with tofacitinib.
Methods:
Tofacitinib 5 and 10 mg twice daily and placebo data were pooled from two Phase 3 studies (OPAL Broaden [12 months; ClinicalTrials.gov identifier NCT01877668]; OPAL Beyond [6 months; ClinicalTrials.gov identifier NCT01882439]); patients received one background conventional synthetic diseaseâmodifying antirheumatic drug. Patients were stratified by baseline presence/absence of MetS. Efficacy and safety were reported to month 3 (tofacitinib and placebo) and 6 (tofacitinib only). Efficacy outcomes included: American College of Rheumatology (ACR)20/50/70, Health Assessment QuestionnaireâDisability Index (HAQâDI) response, Psoriasis Area Severity Index (PASI)75 response, and enthesitis/dactylitis resolution rates; and changes from baseline (Î) in Câreactive protein, HAQâDI, Patientâs/Physicianâs Global Assessment of Arthritis, and patientâreported outcomes. Safety outcomes included treatmentâemergent allâcausality adverse events (AEs), Î in lipid/hepatic values, and liver parameter increases.
Results:
Of 710 patients, 41.4% (n = 294) had baseline MetS. All efficacy outcomes improved with both tofacitinib doses versus placebo, to month 3; tofacitinib efficacy was consistent to month 6, regardless of MetS status. MetS did not appear to affect the incidence of AEs or Î in lipid/hepatic values with tofacitinib up to month 3 or 6. Arterial thromboembolism and myocardial infarction (adjudicated major adverse cardiovascular events) were each reported once in tofacitinibâtreated patients with MetS.
Conclusion:
Regardless of baseline MetS status, tofacitinib showed greater efficacy versus placebo in patients with active PsA. The tofacitinib safety profile appeared similar in patients with versus without MetS
Process Algebra with Layers: Multi-scale Integration Modelling applied to Cancer Therapy
We present a novel Process Algebra designed for multi-scale integration modelling: Process Algebra with Layers (PAL). The unique feature of PAL is the modularisation of scale into integrated layers: Object and Population. An Object can represent a molecule, organelle, cell, tissue, organ or any organism. Populations hold specific types of Object, for example, life stages, cell phases and infectious states. The syntax and semantics of this novel language are presented. A PAL model of the multi-scale system of cell growth and damage from cancer treatment is given. This model allows the analysis of different scales of the system. The Object and Population levels give insight into the length of a cell cycle and cell population growth respectively. The PAL model results are compared to wet laboratory survival fractions of cells given different doses of radiation treatment [1]. This comparison shows how PAL can be used to aid in investigations of cancer treatment in systems biology
Observations of the Askaryan Effect in Ice
We report on the first observations of the Askaryan effect in ice: coherent impulsive radio Cherenkov radiation from the charge asymmetry in an electromagnetic (EM) shower. Such radiation has been observed in silica sand and rock salt, but this is the first direct observation from an EM shower in ice. These measurements are important since the majority of experiments to date that rely on the effect for ultra-high energy neutrino detection are being performed using ice as the target medium. As part of the complete validation process for the Antarctic Impulsive Transient Antenna (ANITA) experiment, we performed an experiment at the Stanford Linear Accelerator Center (SLAC) in June 2006 using a 7.5 metric ton ice target, yielding results fully consistent with theoretical expectations
New Limits on the Ultra-high Energy Cosmic Neutrino Flux from the ANITA Experiment
We report initial results of the first flight of the Antarctic Impulsive
Transient Antenna (ANITA-1) 2006-2007 Long Duration Balloon flight, which
searched for evidence of a diffuse flux of cosmic neutrinos above energies of 3
EeV. ANITA-1 flew for 35 days looking for radio impulses due to the Askaryan
effect in neutrino-induced electromagnetic showers within the Antarctic ice
sheets. We report here on our initial analysis, which was performed as a blind
search of the data. No neutrino candidates are seen, with no detected physics
background. We set model-independent limits based on this result. Upper limits
derived from our analysis rule out the highest cosmogenic neutrino models. In a
background horizontal-polarization channel, we also detect six events
consistent with radio impulses from ultra-high energy extensive air showers.Comment: 4 pages, 2 table
Characterization of Leishmania spp. causing cutaneous leishmaniasis in Manaus, Amazonas, Brazil
In the State of Amazonas, American tegumentary leishmaniasis is endemic and presents a wide spectrum of clinical variability due to the large diversity of circulating species in the region. Isolates from patients in Manaus and its metropolitan region were characterized using monoclonal antibodies and isoenzymes belonging to four species of the parasite: Leishmania (Viannia) guyanensis, 73% (153/209); Leishmania (Viannia) braziliensis, 14% (30/209); Leishmania (Leishmania) amazonensis, 8% (17/209); and Leishmania (Viannia) naiffii, 4% (9/209). The most prevalent species was L. (V.) guyanensis. The principal finding of this study was the important quantity of infections involving more than one parasite species, representing 14% (29/209) of the total. The findings obtained in this work regarding the parasite are further highlighted by the fact that these isolates were obtained from clinical samples collected from single lesions
Physiological Stress and Refuge Behavior by African Elephants
Physiological stress responses allow individuals to adapt to changes in their status or surroundings, but chronic exposure to stressors could have detrimental effects. Increased stress hormone secretion leads to short-term escape behavior; however, no studies have assessed the potential of longer-term escape behavior, when individuals are in a chronic physiological state. Such refuge behavior is likely to take two forms, where an individual or population restricts its space use patterns spatially (spatial refuge hypothesis), or alters its use of space temporally (temporal refuge hypothesis). We tested the spatial and temporal refuge hypotheses by comparing space use patterns among three African elephant populations maintaining different fecal glucocorticoid metabolite (FGM) concentrations. In support of the spatial refuge hypothesis, the elephant population that maintained elevated FGM concentrations (iSimangaliso) used 20% less of its reserve than did an elephant population with lower FGM concentrations (Pilanesberg) in a reserve of similar size, and 43% less than elephants in the smaller Phinda reserve. We found mixed support for the temporal refuge hypothesis; home range sizes in the iSimangaliso population did not differ by day compared to nighttime, but elephants used areas within their home ranges differently between day and night. Elephants in all three reserves generally selected forest and woodland habitats over grasslands, but elephants in iSimangaliso selected exotic forest plantations over native habitat types. Our findings suggest that chronic stress is associated with restricted space use and altered habitat preferences that resemble a facultative refuge behavioral response. Elephants can maintain elevated FGM levels for â„6 years following translocation, during which they exhibit refuge behavior that is likely a result of human disturbance and habitat conditions. Wildlife managers planning to translocate animals, or to initiate other management activities that could result in chronic stress responses, should consider the potential for, and consequences of, refuge behavior
Multifrequency Strategies for the Identification of Gamma-Ray Sources
More than half the sources in the Third EGRET (3EG) catalog have no firmly
established counterparts at other wavelengths and are unidentified. Some of
these unidentified sources have remained a mystery since the first surveys of
the gamma-ray sky with the COS-B satellite. The unidentified sources generally
have large error circles, and finding counterparts has often been a challenging
job. A multiwavelength approach, using X-ray, optical, and radio data, is often
needed to understand the nature of these sources. This chapter reviews the
technique of identification of EGRET sources using multiwavelength studies of
the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray
Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer
Academic Press, 2004. For complete article and higher resolution figures, go
to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd
Control of microwave signals using circuit nano-electromechanics
Waveguide resonators are crucial elements in sensitive astrophysical
detectors [1] and circuit quantum electrodynamics (cQED) [2]. Coupled to
artificial atoms in the form of superconducting qubits [3, 4], they now provide
a technologically promising and scalable platform for quantum information
processing tasks [2, 5-8]. Coupling these circuits, in situ, to other quantum
systems, such as molecules [9, 10], spin ensembles [11, 12], quantum dots [13]
or mechanical oscillators [14, 15] has been explored to realize hybrid systems
with extended functionality. Here, we couple a superconducting coplanar
waveguide resonator to a nano-coshmechanical oscillator, and demonstrate
all-microwave field controlled slowing, advancing and switching of microwave
signals. This is enabled by utilizing electromechanically induced transparency
[16-18], an effect analogous to electromagnetically induced transparency (EIT)
in atomic physics [19]. The exquisite temporal control gained over this
phenomenon provides a route towards realizing advanced protocols for storage of
both classical and quantum microwave signals [20-22], extending the toolbox of
control techniques of the microwave field.Comment: 9 figure
Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy
Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies
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