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The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.
Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.
Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.
In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.
The Omani basement is located spatially distant from the dominantly juvenile Arabian–Nubian Shield (ANS) to its west, and its relationship to the amalgamation of those arc terranes has yet to be properly constrained. The Jebel Ja'alan (NE Oman) basement inlier provides an excellent opportunity to better understand the Neoproterozoic tectonic geography of Oman and its relationship to the ANS. To understand the origin of this basement inlier, we present new radiogenic isotopic data from igneous bodies in Jebel Ja'alan. U–Pb and 40Ar/39Ar geochronological data are used to constrain the timing of magmatism and metamorphism in the jebel. Positive εHf and εNd values indicate a juvenile origin for the igneous lithologies. Phase equilibria modelling is used to constrain the metamorphic conditions recorded by basement. Pressure–temperature (P–T) pseudosections show that basement schists followed a clockwise P–T path, reaching peak metamorphic conditions of c. 650–700°C at 4–7.5 kbar, corresponding to a thermal gradient of c. 90–160°C/kbar. From the calculated thermal gradient, in conjunction with collected trace-element data, we interpret that the Jebel Ja'alan basement formed in an arc environment. Geochronological data indicate that this juvenile arc formed during Tonian time and is older than basement further west in Oman. We argue that the difference in timing is related to westwards arc accretion and migration, which implies that the Omani basement represents its own tectonic domain separate to the ANS and may be the leading edge of the Neoproterozoic accretionary margin of India.
A species in the Bactrocera dorsalis (Hendel) complex was detected in Kenya during 2003 and classified as Bactrocera invadens Drew, Tsuruta & White. Having spread rapidly throughout Africa, it threatens agriculture due to crop damage and loss of market access. In a recent revision of the B. dorsalis complex, B. invadens was incorporated into the species B. dorsalis. The potential distribution of B. dorsalis has been previously modelled. However, previous models were based on presence data and did not incorporate information on the seasonal phenology of B. dorsalis, nor on the possible influence that irrigation may have on its distribution. Methyl eugenol-baited traps were used to collect B. dorsalis in Africa. Seasonal phenology data, measured as fly abundance throughout the year, was related to each location's climate to infer climatic growth response parameters. These functions were used along with African distribution records and development studies to fit the niche model for B. dorsalis, using independent global distribution records outside Africa for model validation. Areas at greatest risk of invasion by B. dorsalis are South and Central America, Mexico, southernmost USA, parts of the Mediterranean coast, parts of Southern and Eastern Australia and New Zealand's North Island. Under irrigation, most of Africa and Australia appear climatically suitable.
The Murchison Widefield Array is a Square Kilometre Array Precursor. The telescope is located at the Murchison Radio–astronomy Observatory in Western Australia. The MWA consists of 4 096 dipoles arranged into 128 dual polarisation aperture arrays forming a connected element interferometer that cross-correlates signals from all 256 inputs. A hybrid approach to the correlation task is employed, with some processing stages being performed by bespoke hardware, based on Field Programmable Gate Arrays, and others by Graphics Processing Units housed in general purpose rack mounted servers. The correlation capability required is approximately 8 tera floating point operations per second. The MWA has commenced operations and the correlator is generating 8.3 TB day−1 of correlation products, that are subsequently transferred 700 km from the MRO to Perth (WA) in real-time for storage and offline processing. In this paper, we outline the correlator design, signal path, and processing elements and present the data format for the internal and external interfaces.
We surveyed infection prevention programs in 16 hospitals for hospital-associated methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, extended-spectrum β-lactamase, and multidrug-resistant Acinetobacter acquisition, as well as hospital-associated MRSA bacteremia and Clostridium difficile infection based on defining events as occurring >2 days versus >3 days after admission. The former resulted in significantly higher median rates, ranging from 6.76% to 45.07% higher
Infect Control Hosp Epidemiol 2014;35(11):1417–1420
In the Kingdom of Saudi Arabia (KSA), Old World cutaneous leishmaniasis (CL) is mainly caused by Leishmania major and Leishmania tropica parasites. Diagnosis of CL is predominately made by clinicians, who at times fail to detect the disease and are unable to identify parasite species. Here, we report the development of a chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) to measure the levels of anti-α-galactosyl antibodies in human sera. Using this assay, we have found that individuals infected with either Leishmania spp. had significantly elevated levels (up to 9-fold higher) of anti-α-Gal IgG compared to healthy control individuals. The assay sensitivity was 96% for L. major (95% CI; 94–98%) and 91% for L. tropica (95% CI; 86–98%) infections and therefore equivalent to restriction fragment length polymorphism-polymerase chain reaction analysis of parasite ITS1 gene. In addition, the assay had higher sensitivity than microscopy analysis, which only detected 68 and 45% of the L. major and L. tropica infections, respectively. Interestingly, up to 2 years following confirmed CL cure individuals had 28-fold higher levels of anti-α-Gal IgG compared to healthy volunteers. Monitoring levels of anti-α-Gal antibodies can be exploited as both a diagnostic tool and as a biomarker of cure of Old World CL in disease elimination settings.
A theoretical investigation has been made of obliquely propagating nonlinear electrostatic shock structures. The reductive perturbation method has been used to derive the Korteweg-de Vries-Burger (KdV-Burger) equation for dust acoustic shock waves in a homogeneous system of a magnetized collisionless plasma comprising a four-component dusty plasma with massive, micron-sized, positively, negatively dust grains and non-extensive electrons and ions. The effect of dust viscosity coefficients of charged dusty plasma of opposite polarity and the non-extensive parameters of electrons and ions have been studied. The behavior of the oscillatory and monotonic shock waves in dusty plasma has been investigated. It has been found that the presence of non-extensive parameters significantly modified the basic properties of shock structures in space environments.
Significant new opportunities for astrophysics and cosmology have been identified at low radio frequencies. The Murchison Widefield Array is the first telescope in the southern hemisphere designed specifically to explore the low-frequency astronomical sky between 80 and 300 MHz with arcminute angular resolution and high survey efficiency. The telescope will enable new advances along four key science themes, including searching for redshifted 21-cm emission from the EoR in the early Universe; Galactic and extragalactic all-sky southern hemisphere surveys; time-domain astrophysics; and solar, heliospheric, and ionospheric science and space weather. The Murchison Widefield Array is located in Western Australia at the site of the planned Square Kilometre Array (SKA) low-band telescope and is the only low-frequency SKA precursor facility. In this paper, we review the performance properties of the Murchison Widefield Array and describe its primary scientific objectives.
The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80–300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ~3-km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper, the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised.
Indoor radon concentrations were measured in four well-known spas of Tunisia using
nuclear track detectors. The radon concentrations in these spas were found to be in the
range of 19 - 870 Bq.m-3. The equilibrium factor F between radon and its
progeny was found to vary in the range of 0.2 - 0.5, depending upon the ventilation rates
within the buildings of the spas. Using the exposure-dose conversion factor, the effective
doses to patients and workers were estimated and the dose was found to vary in the range
3.7 × 10-3 - 12.5 × 10-3 mSv.y-1 and 0.45 - 1.5 mSv.y-1
for patients and workers, respectively. These values are well inside the limit recommended
for the annual dose limit of 20 mSv.y-1 for an occupational worker. The radium
content in the groundwater of all four spas was measured and the results showed no
correlation between the 226Ra concentration in water and radon concentration in
indoor air of the investigated spas.
This paper focuses on the modelling of a SiC-JFET. The novelty aspect is the
dependence on temperature. An accurate model has been used in a previous
work and an identification procedure for the main model parameters has been
demonstrated. Readers have asked for a more advanced SiC JFET
temperature-dependent model. A limitation of the current model versus
temperature is verified and explained in order to introduce the necessity of
a new temperature dependence model. A more advanced model is then considered
and a comparative study between experiment and simulation of the device is
established. The characteristics of three SiC JFETs devices are considered
from experimental and simulation point-of-view. Simulations results clearly
replicate the experimental data at different temperatures and a new validity
approach, namely validity maps, is proposed. Validity domains are discussed.
Indoor radon measurements were carried out in 30 elementary schools in Tunis, the capital
city of Tunisia, during the winter months of December 2008 to early March 2009. Two
classrooms, one each from ground floor and first floor were chosen from each school making
a total of 60 classrooms. In some of the classrooms, two detectors (open and closed) were
used to measure the concentrations of radon as well as radon and its progeny to allow the
calculations of the equilibrium factors. Nuclear track detectors type LR-115 (Kodalpha)
were used for the measurements. The results show that the radon concentration levels are
low in the range of 6–169 Bq m-3 with a mean value of 26.9 Bq m-3.
The annual effective dose was found to vary between 0.025–0.715 mSv y-1 for
teachers while the range for pupils was from 0.019–0.525 mSv y-1. These values
are within the ICPR recommended values.
The introduction of large single crystal and high performance CdZnTe (CZT) grown by the traveling heater method (THM) in 2006 has defied conventional myths about the capability of this crystal growth method with respect to the production of spectroscopic grade CZT and its commercialization prospect in medical imaging application. Since then, a lot of progresses have been made, both in the crystal growth and the devices sides. This paper focuses on the development of THM CZT in recent years. Crystalline defects which challenge the thickness scalability of large volume CZT detectors along with efforts and achievements in overcoming these challenges are discussed. Advances in THM CZT crystal growth include 100mm diameter ingot and state-of-the-art device fabrication will also be presented.
In this study, we report on the diffusion of neodymium (Nd) and erbium (Er) into n-type and undoped GaN and subsequent measurements of the room-temperature (RT) magnetic and optical properties. The diffusion profile has been measured via secondary ion mass spectroscopy (SIMS) with rare-earth (RE) concentration yields of up to 1×1018/cm3. The ferromagnetic properties were measured using an alternating gradient magnetometer (AGM) giving a saturation magnetization (Ms) of up to 3.17emu/cm3 for the RE-diffused layer. The photoluminescence (PL) emission of the Nd-diffused and Er-diffused GaN is observable in the near-infrared (NIR) and infrared (IR) regions of the spectrum, respectively. The Nd-diffused GaN samples show NIR emission at 1064nm and 1350nm, while Er-diffused GaN samples have IR emission at 1546nm. This appears to be the first successful result of Nd diffusion doping into GaN crystals, and the first demonstration of above RT ferromagnetism involving GaN diffused with Nd. Details of our ferromagnetic and optical emission studies, related to the RE diffusion into GaN, are presented.
Characteristics of strained layer superlattices (SLS) consisting of alternating layers InxGa1-xAs and GaAs1-yPy are examined for use in high efficiency solar cells. The effects of SLS quantum barrier widths on tunneling probability and short circuit current are discussed through analysis of J-V and spectral response measurements. Results indicate a threshold barrier thickness for which tunneling effects are deleterious. Effect of the number of SLS periods incorporated into a p-i-n structure and maximum number of periods are presented through spectral response and CV analysis. It is demonstrated that SLS show increasing responsivity with increasing number of periods due to higher absorption. CV analysis is performed to determine zero bias depletion widths for verifying appropriate number of SLS periods and fully depleted SLS region.
InGaAs can be used to enhance the response of solar cells past the 1.43 eV cutoff of GaAs. Strained-layer superlattice (SLS) structures with high indium and phosphorus compositions (up to 35% and 68% respectively) have been grown successfully. SLS solar cells with indium and high phosphorus compositions (up to 15% and 85% respectively) have been grown successfully. The spectral response of the solar cells has been extended to as low as 1.27 eV. This enhancement is also shown by an increase in the short circuit current, with a small reduction in the short circuit voltage as compared to standard GaAs p-n junction for AM1.5 and one sun.
Dark current curves show the extent of recombination in the superlattice. The reverse saturation current in the recombination region (0.2-0.8 V) was determined using a non-linear least squares fitting routine. An Arrhenius plot was generated by finding the reverse saturation current over a temperature range of 300-370 K. The low recombination devices show non-ideality constants of 1.7 with activation energies of 1.3-1.4 eV. The high recombination devices have non-ideality constants (˜2.3) and lower activation energies of 1.1 eV.
The authors present preliminary results of geophysical and palynological reconnaissance at the Tell El Dabaa, eastern Nile Delta. The geophysical survey reveals the presence of floodbasins, levees and channel deposits. Low palynomorph concentrations probably result from the high sedimentation rate and mean that further work is needed on the methods for palynological study in the region.
Various REE-Sr-(Pb)-crandallites, uraninite, and coffinite in the near-field of the 2 Ga old super-gene-altered Bangombé U-deposit and its natural fission reactor (RZB) have been examined. The crandallite minerals may have formed during syncriticality host-rock alteration, continous alteration of phosphates, episodic Pb-loss and/or supergene weathering. Coffinitization with P2O5 and SO4-substitution has occurred immediately below RZB and resulted in extensive loss of U (≤ 46%) and enrichment of Ce (≤ 190%) and Nd (≤ 780%). Additional loss of U during coffinitization also may have occurred due to dissolution. Current alteration under oxidizing conditions has resulted in partial dissolution of uraninite and coffinite and the formation of uranyl phases. Despite supergene alteration, the hydrogeochemistry (3.09 ppt U [235U/238U = 0.7012 to 0.7019%], 4.96 ppt Ce, and 1.92 ppt Nd) suggests a remarkable retardation of lanthanides and depleted uranium by REE-Sr-(Pb)-crandallites, uraninite, coffinite, and uranyl phases at RZB.
Two groups each of six lambs of the fat-tailed Naeimi breed, well adapted to a semi-arid climate, were housed under semi-controlled temperature (43·2 to 43·8°C) with low relative humidity (<0·8). After a 1-week adaptation period, the first group (control) was injected subcutaneously with 1 ml vehicle solution of 40% ethanol in saline, twice daily at 08.00 and 17.00 hfor the 11-day experimental period. In the other group, each lamb was injected daily for 6 days with 0·18 mg/kg per day of the prolactin inhibitor, 2 bromo-a-ergocryptine (CB154) dissolved in the vehicle solution. Treatment during the next 5 days was as for the control animals. Rectal temperature (RT), respiratory rate (RR), water and food intakes were recorded before injections. Daily average data were used in the statistical analysis, except those of the 1st day of bromocryptine injection. Lambs of the control group were able to maintain their RT (39·5 (s.e. 0·04) °C) during heat exposure, but those treated with the bromocryptine could not (40·3 (s.e. 0·07) °C). However, the latter group continued to respire more rapidly (P < 0·01) after cessation of the CB154 treatment, reducing their body temperature slightly (39·9 (s.e. 0·06) °C). This shows that, following prolactin suppression, heat-stressed lambs were unable to regulate their body temperature despite their RR. Water intake did not change during bromocryptine treatment, but the ratio of water to dry-matter intake did increase due to lower food consumption. These results suggest that prolactin might have an important role in thermoregulation of the fat-tailed male sheep during elevated ambient temperature.