182 research outputs found
Settlement Archaeology in the Jauja Region of Peru: Evidence from the Early Intermediate Period; A Report on the 1986 Field Season
Freeze-In Production of FIMP Dark Matter
We propose an alternate, calculable mechanism of dark matter genesis,
"thermal freeze-in," involving a Feebly Interacting Massive Particle (FIMP)
interacting so feebly with the thermal bath that it never attains thermal
equilibrium. As with the conventional "thermal freeze-out" production
mechanism, the relic abundance reflects a combination of initial thermal
distributions together with particle masses and couplings that can be measured
in the laboratory or astrophysically. The freeze-in yield is IR dominated by
low temperatures near the FIMP mass and is independent of unknown UV physics,
such as the reheat temperature after inflation. Moduli and modulinos of string
theory compactifications that receive mass from weak-scale supersymmetry
breaking provide implementations of the freeze-in mechanism, as do models that
employ Dirac neutrino masses or GUT-scale-suppressed interactions. Experimental
signals of freeze-in and FIMPs can be spectacular, including the production of
new metastable coloured or charged particles at the LHC as well as the
alteration of big bang nucleosynthesis.Comment: 30 pages, 7 figures, PDFLaTex. References adde
Dynamic heterogeneities in the out-of-equilibrium dynamics of simple spherical spin models
The response of spherical two-spin interaction models, the spherical
ferromagnet (s-FM) and the spherical Sherrington-Kirkpatrick (s-SK) model, is
calculated for the protocol of the so-called nonresonant hole burning
experiment (NHB) for temperatures below the respective critical temperatures.
It is shown that it is possible to select dynamic features in the
out-of-equilibrium dynamics of both models, one of the hallmarks of dynamic
heterogeneities. The behavior of the s-SK model and the s-FM in three
dimensions is very similar, showing dynamic heterogeneities in the long time
behavior, i.e. in the aging regime. The appearence of dynamic heterogeneities
in the s-SK model explicitly demonstrates that these are not necessarily
related to {\it spatial} heterogeneities. For the s-FM it is shown that the
nature of the dynamic heterogeneities changes as a function of dimensionality.
With incresing dimension the frequency selectivity of the NHB diminishes and
the dynamics in the mean-field limit of the s-FM model becomes homogeneous.Comment: 16 pages, 8 figure
Decaying into the Hidden Sector
The existence of light hidden sectors is an exciting possibility that may be
tested in the near future. If DM is allowed to decay into such a hidden sector
through GUT suppressed operators, it can accommodate the recent cosmic ray
observations without over-producing antiprotons or interfering with the
attractive features of the thermal WIMP. Models of this kind are simple to
construct, generic and evade all astrophysical bounds. We provide tools for
constructing such models and present several distinct examples. The light
hidden spectrum and DM couplings can be probed in the near future, by measuring
astrophysical photon and neutrino fluxes. These indirect signatures are
complimentary to the direct production signals, such as lepton jets, predicted
by these models.Comment: 40 pages, 5 figure
Virus-specific T cells engineered to coexpress tumor-specific receptors: Persistence and antitumor activity in individuals with neuroblastoma
Cytotoxic T lymphocytes (CTLs) directed to nonviral tumor-associated antigens do not survive long term and have limited antitumor activity in vivo, in part because such tumor cells typically lack the appropriate costimulatory molecules. We therefore engineered Epstein-Barr virus (EBV)-specific CTLs to express a chimeric antigen receptor directed to the diasialoganglioside GD2, a nonviral tumor-associated antigen expressed by human neuroblastoma cells. We reasoned that these genetically engineered lymphocytes would receive optimal costimulation after engagement of their native receptors, enhancing survival and antitumor activity mediated through their chimeric receptors. Here we show in individuals with neuroblastoma that EBV-specific CTLs expressing a chimeric GD2-specific receptor indeed survive longer than T cells activated by the CD3-specific antibody OKT3 and expressing the same chimeric receptor but lacking virus specificity. Infusion of these genetically modified cells seemed safe and was associated with tumor regression or necrosis in half of the subjects tested. Hence, virus-specific CTLs can be modified to function as tumor-directed effector cells
Enhanced glycemic control with combination therapy for type 2 diabetes in primary care
Type 2 diabetes mellitus is an increasingly common medical problem for primary care clinicians to address. Treatment of diabetes has evolved from simple replacement of insulin (directly or through insulin secretagogs) through capture of mechanisms such as insulin sensitizers, alpha-glucosidase inhibitors, and incretins. Only very recently has recognition of the critical role of the gastrointestinal system as a major culprit in glucose dysregulation been established. Since glycated hemoglobin A1c reductions provide meaningful risk reduction as well as improved quality of life, it is worthwhile to explore evolving paths for more efficient use of the currently available pharmacotherapies. Because diabetes is a progressive disease, even transiently successful treatment will likely require augmentation as the disorder progresses. Pharmacotherapies with complementary mechanisms of action will be necessary to achieve glycemic goals. Hence, clinicians need to be well informed about the various noninsulin alternatives that have been shown to be successful in glycemic goal attainment. This article reviews the benefits of glucose control, the current status of diabetes control, pertinent pathophysiology, available pharmacological classes for combination, limitations of current therapies, and suggestions for appropriate combination therapies, including specific suggestions for thresholds at which different strategies might be most effectively utilized by primary care clinicians
From chemical gardens to chemobrionics
Chemical gardens are perhaps the best example in chemistry of a
self-organizing nonequilibrium process that creates complex
structures. Many different chemical systems and materials can
form these self-assembling structures, which span at least 8
orders of magnitude in size, from nanometers to meters. Key to
this marvel is the self-propagation under fluid advection of
reaction zones forming semipermeable precipitation membranes
that maintain steep concentration gradients, with osmosis and
buoyancy as the driving forces for fluid flow. Chemical gardens
have been studied from the alchemists onward, but now in the
21st century we are beginning to understand how they can lead
us to a new domain of self-organized structures of semipermeable
membranes and amorphous as well as polycrystalline solids
produced at the interface of chemistry, fluid dynamics, and
materials science. We propose to call this emerging field
chemobrionics
Outcome of COVID-19 in hospitalised immunocompromised patients: an analysis of the WHO ISARIC CCP-UK prospective cohort study
Background
Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic.
Methods and findings
We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p 80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent.
Conclusions
Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group
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