52 research outputs found
T10B9 monoclonal antibody: A short-acting nonstimulating monoclonal antibody that spares γδ T-cells and treats and prevents cellular rejection
T10B9.1A-31/MEDI-500 is a nonmitogenic immunoglobulin M kappa murine monoclonal antibody (mAb) directed against the alpha-beta (αβ) heterodimer of the T-lymphocyte receptor complex. The hybridoma was first produced by fusing spleen cells from BALB/C mice immunized with human peripheral blood T-lymphocytes with SP2/O-Ag14 mutant myeloma cells. The mAb is produced and purified using multistep ion exchange and molecular sieve chromatography protocols. T10B9 has been used successfully to treat acute cellular rejection in renal transplantation and as an immunosuppression induction agent in heart and simultaneous kidney-pancreas transplantation. Because T10B9 is nonmitogenic and causes minimal cytokine release, both treatment of rejection and induction of immunosuppression were accomplished with significantly fewer and milder untoward effects (cytokine release syndrome) than its comparator OKT3. Since T10B9 is directed against the αβ heterodimer of the CD3 epitope, it spares the gamma delta (γδ) region. These gamma delta (γδ) T cells have a unique role in the immune response controlling many serious human diseases and perhaps facilitating the development of immunologic tolerance. T10B9 has a relatively short duration of action, depleting T cells for only 10 to 14 days, unlike the protracted depletion seen with thymoglobulin and Campath-1H. There is no B-lymphocyte depletion with T10B9 as there is with both of the aforementioned reagents. The lack of prolonged lymphocyte depletion may account for less infection observed with T10B9 treatment
SiC Based Beam Monitoring System for Particle Rates from kHz to GHz
The extremely low dark current of silicon carbide (SiC) detectors, even after
high-fluence irradiation, was utilized to develop a beam monitoring system for
a wide range of particle rates, i.e., from the kHz to the GHz regime. The
system is completely built from off-the-shelve components and is focused on
compactness and simple deployment. Beam tests using a 50 um thick SiC detector
reveal, that for low fluences, single particles can be detected and counted.
For higher fluences, beam properties were extracted from beam cross sections
using a silicon strip detector. Overall accurate results were achieved up to a
particle rate of 109 particles per second
Performance of neutron-irradiated 4H-Silicon Carbide diodes subjected to Alpha radiation
The unique electrical and material properties of 4H-silicon-carbide (4H-SiC)
make it a promising candidate material for high rate particle detectors. In
contrast to the ubiquitously used silicon (Si), 4H-SiC offers a higher carrier
saturation velocity and larger breakdown voltage, enabling a high intrinsic
time resolution and mitigating pile-up effects. Additionally, as radiation
hardness requirements grow more demanding, wide-bandgap materials such as
4H-SiC could offer better performance. In this work, the detector performance
of 50 micron thick 4H-SiC p-in-n planar pad sensors was investigated at room
temperature, using an 241Am alpha source at reverse biases of up to 1100 V.
Samples subjected to neutron irradiation with fluences of up to 1e16/cm^2 were
included in the study in order to quantify the radiation hardness properties of
4H-SiC. The obtained results are compared to previously performed UV-TCT
studies. Samples exhibit a drop in charge collection efficiency (CCE) with
increasing irradiation fluence, partially compensated at high reverse bias
voltages far above full depletion voltage. A plateau of the collected charges
is observed in accordance with the depletion of the volume the alpha particles
penetrate for an unirradiated reference detector. For the neutron-irradiated
samples, such a plateau only becomes apparent at higher reverse bias. For the
highest investigated fluence, CCE behaves almost linearly with increasing
reverse bias. Compared to UV-TCT measurements, the reverse bias required to
deplete a sensitive volume covering full energy deposition is lower, due to the
small penetration depth of the alpha particles. At the highest reverse bias,
the measured CCE values agree well with earlier UV-TCT studies, with
discrepancies between 1% and 5%.Comment: 10 pages (8 without references), 6 figures, 1 table, to be published
in the Proceedings Section of Journal of Instrumentation (JINST) as a
proceeding of iWoRiD202
Fantastically reasonable: ambivalence in the representation of science and technology in super-hero comics
A long-standing contrast in academic discussions of science concerns its perceived disenchanting or enchanting public impact. In one image, science displaces magical belief in unknowable entities with belief in knowable forces and processes and reduces all things to a single technical measure. In the other, science is itself magically transcendent, expressed in technological adulation and an image of scientists as wizards or priests. This paper shows that these contrasting images are also found in representations of science in super-hero comics, which, given their lowly status in Anglo-American culture, would seem an unlikely place to find such commonality with academic discourse. It is argued that this is evidence that the contrast constitutes an ambivalence arising from the dilemmas that science poses; they are shared rhetorics arising from and reflexively feeding a set of broad cultural concerns. This is explored through consideration of representations of science at a number of levels in the comics, with particular focus on the science-magic constellation, and enchanted and disenchanted imagery in representations of technology and scientists. It is concluded that super-hero comics are one cultural arena where the public meaning of science is actively worked out, an activity that unites “expert” and “non-expert” alike
Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016
BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016.
METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone.
FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, an
Study 2: tacrolimus as secondary intervention versus continuation of cyclosporine in patients at risk for chronic renal allograft failure results in improved renal function, decreased cardiovascular risk, and no increased risk for diabetes
Long-term Follow-up of Kidney Transplant Recipients in the Spare-the-Nephron-Trial
In the Spare-the-Nephron (STN) Study, kidney transplant recipients randomized about 115 days posttransplant to convert from CNI (calcineurin inhibitor)/MMF to sirolimus (SRL)/MMF had a significantly greater improvement in measured GFR (mGFR) at 12 months compared with those kept on CNI/MMF. The difference at 24 months was not statistically significant. From 14 top enrolling centers, 128 of 175 patients identified with a functioning graft at 2 years consented to enroll in an observational, noninterventional extension study to collect retrospectively and prospectively annual follow-up data for the interval since baseline (completion of the parent STN study at 24 months posttransplant). Overall, 11 patients died, including 5 (7.6%) in the SRL/MMF group and 6 (9.7%) in the CNI/MMF group. Twenty-two grafts have been lost including 10 (15.2%) in the SRL/MMF arm and 12 (19.4%) in the CNI/MMF arm. Death and chronic rejection were the most common causes of graft loss in both arms. There were modestly more cardiovascular events in the MMF/SRL group. Estimated creatinine clearance (Cockcroft-Gault) from baseline out to 6 additional years (8 years posttransplant, ITT analysis, SRL/MMF, n = 34; CNI/MMF, n = 26) was 63.2 ± 28.5 mL/min/1.73 m in the SRL/MMF group and 59.2 ± 27.2 mL/min/1.73 m in the CNI/MMF group and was not statistically significant, but there is a clinically meaningful trend for improved long-term renal function in the SRL/MMF group compared with the CNI/MMF group. The long-term decision for immunosuppression needs to be carefully individualized
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