273 research outputs found
Functional Tolerance is Maintained Despite Proliferation of CD4 T Cells after Encounter with Tissue-derived Antigen
Since negative selection in the thymus is incomplete, some self-reactive T cells are able to mature and seed the periphery. To study how these T cells interact following encounter with the self-protein they recognize in the periphery, we have developed an adoptive transfer system in which HEL-specific TCR transgenic CD4 T cells are transferred to mice expressing HEL protein in the pancreas under the control of the rat insulin promoter. Here we show that after adoptive transfer of HEL-specific T cells functional tolerance is maintained despite evidence that the T cells encounter and respond to pancreas-expressed antigen. Even the provision of an additional activation stimulus by peripheral immunization with HEL protein is insufficient to induce the T cells to cause autoimmune tissue injury. However, in the presence of blocking anti-CTLA-4-mAb, immunized adoptive transfer recipients rapidly developed diabetes. These data suggest that the CTLA-4 pathway regulates the pathogenicity of antigen-specific T cells following a peripheral activation stimulus
Measurement of Changes in Uterine and Fibroid Volume During Treatment of Heavy Menstrual Bleeding (HMB)
The UV/optical spectra of the Type Ia supernova SN 2010jn: a bright supernova with outer layers rich in iron-group elements
Radiative transfer studies of Type Ia supernovae (SNe Ia) hold the promise of
constraining both the time-dependent density profile of the SN ejecta and its
stratification by element abundance which, in turn, may discriminate between
different explosion mechanisms and progenitor classes. Here we present a
detailed analysis of Hubble Space Telescope ultraviolet (UV) and ground-based
optical spectra and light curves of the SN Ia SN 2010jn (PTF10ygu). SN 2010jn
was discovered by the Palomar Transient Factory (PTF) 15 days before maximum
light, allowing us to secure a time-series of four UV spectra at epochs from
-11 to +5 days relative to B-band maximum. The photospheric UV spectra are
excellent diagnostics of the iron-group abundances in the outer layers of the
ejecta, particularly those at very early times. Using the method of 'Abundance
Tomography' we have derived iron-group abundances in SN 2010jn with a precision
better than in any previously studied SN Ia. Optimum fits to the data can be
obtained if burned material is present even at high velocities, including
significant mass fractions of iron-group elements. This is consistent with the
slow decline rate (or high 'stretch') of the light curve of SN 2010jn, and
consistent with the results of delayed-detonation models. Early-phase UV
spectra and detailed time-dependent series of further SNe Ia offer a promising
probe of the nature of the SN Ia mechanism.Comment: 17 pages, 9 figures (v3: several small updates to content including
models; v2: metadata fixed), MNRAS, in pres
Building the Field of Health Policy and Systems Research: Social Science Matters
In the second in a series of articles addressing the current challenges and opportunities for the development of Health Policy and Systems Research (HPSR), Lucy Gilson and colleagues argue the importance of insights from the social sciences
Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis
Background
People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID.
Methods
In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity.
Findings
We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk.
Interpretation
Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID
The effects of dust on the optical and infrared evolution of SN 2004et
We present an analysis of multi-epoch observations of the Type II-P supernova
SN 2004et. New and archival optical spectra of SN 2004et are used to study the
evolution of the Halpha and [O I] 6300A line profiles between days 259 and 646.
Mid-infrared imaging was carried out between 2004 to 2010. We include Spitzer
`warm' mission photometry at 3.6 and 4.5um obtained on days 1779, 1931 and
2151, along with ground-based and HST optical and near-infrared observations
obtained between days 79 and 1803. Multi-wavelength light curves are presented,
as well as optical-infrared spectral energy distributions (SEDs) for multiple
epochs. Starting from about day 300, the optical light curves provide evidence
for an increasing amount of circumstellar extinction attributable to newly
formed dust, with the additional extinction reaching 0.8-1.5 magnitudes in the
V-band by day 690. The overall SEDs were fitted with multiple blackbody
components, in order to investigate the luminosity evolution of the supernova,
and then with Monte Carlo radiative transfer models using smooth or clumpy dust
distributions, in order to estimate how much new dust condensed in the ejecta.
The luminosity evolution was consistent with the decay of 56Co in the ejecta up
until about day 690, after which an additional emission source is required, in
agreement with the findings of Kotak et al. (2009). Clumped dust density
distributions consisting of 20% amorphous carbons and 80% silicates by mass
were able to match the observed optical and infrared SEDs, with dust masses
that increased from 8x10^{-5} Msun on day 300 to 1.5x10^{-3} Msun on day 690,
still significantly lower than the values needed for core collapse supernovae
to make a significant contribution to the dust enrichment of galaxies.Comment: 24 pages, 12 figures, 9 tables, published in MNRA
IL-21 shapes germinal center polarization via light zone B cell selection and cyclin D3 upregulation
Hubble Space Telescope studies of low-redshift Type Ia supernovae: Evolution with redshift and ultraviolet spectral trends
We present an analysis of the maximum light, near ultraviolet (NUV; 2900-5500
A) spectra of 32 low redshift (0.001<z<0.08) Type Ia supernovae (SNe Ia),
obtained with the Hubble Space Telescope (HST). We combine this spectroscopic
sample with high-quality gri light curves obtained with robotic telescopes to
measure photometric parameters, such as stretch, optical colour, and
brightness. By comparing our data to a comparable sample of SNe Ia at
intermediate-z (0.4<z<0.9), we detect modest spectral evolution (3-sigma), in
the sense that our mean low-z NUV spectrum has a depressed flux compared to its
intermediate-z counterpart. We also see a strongly increased dispersion about
the mean with decreasing wavelength, confirming the results of earlier surveys.
These trends are consistent with changes in metallicity as predicted by
contemporary SN Ia spectral models. We also examine the properties of various
NUV spectral diagnostics in the individual spectra. We find a general
correlation between stretch and the velocity (or position) of many NUV spectral
features. In particular, we observe that higher stretch SNe have larger Ca II
H&K velocities, that also correlate with host galaxy stellar mass. This latter
trend is probably driven by the well-established correlation between stretch
and stellar mass. We find no trends between UV spectral features and optical
colour. Mean spectra constructed according to whether the SN has a positive or
negative Hubble residual show very little difference at NUV wavelengths,
indicating that the NUV evolution and variation we identify do not directly
correlate with Hubble residuals. Our work confirms and strengthens earlier
conclusions regarding the complex behaviour of SNe Ia in the NUV spectral
region, but suggests the correlations we find are more useful in constraining
progenitor models than improving the use of SNe Ia as cosmological probes.Comment: 22 pages, 14 figures, accepted in MNRAS with minor changes - Spectra
are available on WISeREP, http://www.weizmann.ac.il/astrophysics/wiserep
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