2,481 research outputs found
Validation of Self-Reported Health Literacy Questions Among Diverse English and Spanish-Speaking Populations
BackgroundLimited health literacy (HL) contributes to poor health outcomes and disparities, and direct measurement is often time-intensive. Self-reported HL questions have not been validated among Spanish-speaking and diverse English-speaking populations.ObjectiveTo evaluate three self-reported questions: 1 "How confident are you filling out medical forms?"; 2 "How often do you have problems learning about your medical condition because of difficulty understanding written information?"; and 3 "How often do you have someone help you read hospital materials?" Answers were based on a 5-point Likert scale.DesignThis was a validation study nested within a trial of diabetes self-management support in the San Francisco Department of Public Health.ParticipantsEnglish and Spanish-speaking adults with type 2 diabetes receiving primary care.MethodsUsing the Test of Functional Health Literacy in Adults (s-TOFHLA) in English and Spanish as the reference, we classified HL as inadequate, marginal, or adequate. We calculated the C-index and test characteristics of the three questions and summative scale compared to the s-TOFHLA and assessed variations in performance by language, race/ethnicity, age, and education.Key resultsOf 296 participants, 48% were Spanish-speaking; 9% were White, non-Hispanic; 47% had inadequate HL and 12% had marginal HL. Overall, 57% reported being confident with forms "somewhat" or less. The "confident with forms" question performed best for detecting inadequate (C-index = 0.82, (0.77-0.87)) and inadequate plus marginal HL (C index = 0.81, (0.76-0.86); p<0.01 for differences from other questions), and performed comparably to the summative scale. The "confident with forms" question and scale also performed best across language, race/ethnicity, educational attainment, and age.ConclusionsA single self-reported HL question about confidence with forms and a summative scale of three questions discriminated between Spanish and English speakers with adequate HL and those with inadequate and/or inadequate plus marginal HL. The "confident with forms" question or the summative scale may be useful for estimating HL in clinical research involving Spanish-speaking and English-speaking, chronically-ill, diverse populations
Quantum corrections and black hole spectroscopy
In the work \cite{BRM,RBE}, black hole spectroscopy has been successfully
reproduced in the tunneling picture. As a result, the derived entropy spectrum
of black hole in different gravity (including Einstein's gravity,
Einstein-Gauss-Bonnet gravity and Ho\v{r}ava-Lifshitz gravity) are all evenly
spaced, sharing the same forms as , where physical process is only
confined in the semiclassical framework. However, the real physical picture
should go beyond the semiclassical approximation. In this case, the physical
quantities would undergo higher-order quantum corrections, whose effect on
different gravity shares in different forms. Motivated by these facts, in this
paper we aim to observe how quantum corrections affect black hole spectroscopy
in different gravity. The result shows that, in the presence of higher-order
quantum corrections, black hole spectroscopy in different gravity still shares
the same form as , further confirming the entropy quantum is universal
in the sense that it is not only independent of black hole parameters, but also
independent of higher-order quantum corrections. This is a desiring result for
the forthcoming quantum gravity theory.Comment: 14 pages, no figure, use JHEP3.cls. to be published in JHE
Back reaction, emission spectrum and entropy spectroscopy
Recently, an interesting work, which reformulates the tunneling framework to
directly produce the Hawking emission spectrum and entropy spectroscopy in the
tunneling picture, has been received a broad attention. However, during the
emission process, most related observations have not incorporated the effects
of back reaction on the background spacetime, whose derivations are therefore
not the desiring results for the real physical process. With this point as a
central motivation, in this paper we suitably adapt the \emph{reformulated}
tunneling framework so that it can well accommodate the effects of back
reaction to produce the Hawking emission spectrum and entropy spectroscopy.
Consequently, we interestingly find that, when back reaction is considered, the
Parikh-Wilczek's outstanding observations that, an isolated radiating black
hole has an unitary-evolving emission spectrum that is \emph{not} precisely
thermal, but is related to the change of the Bekenstein-Hawking entropy, can
also be reproduced in the reformulated tunneling framework, meanwhile the
entropy spectrum has the same form as that without inclusion of back reaction,
which demonstrates the entropy quantum is \emph{independent} of the effects of
back reaction. As our final analysis, we concentrate on the issues of the black
hole information, but \emph{unfortunately} find that, even including the
effects of back reaction and higher-order quantum corrections, such tunneling
formalism can still not provide a mechanism for preserving the black hole
information.Comment: 16 pages, no figure, use JHEP3.cls. to be published in JHE
Condensate cosmology in O'Raifeartaigh models
Flat directions charged under an R-symmetry are a generic feature of
O'Raifeartaigh models. Non-topological solitons associated with this symmetry,
R-balls, are likely to form through the fragmentation of a condensate, itself
created by soft terms induced during inflation. In gravity mediated SUSY
breaking R-balls decay to gravitinos, reheating the universe. For gauge
mediation R-balls can provide a good dark matter candidate. Alternatively they
can decay, either reheating or cooling the universe. Conserved R-symmetry
permits decay to gravitinos or gauginos, whereas spontaneously broken
R-symmetry results in decay to visible sector gauge bosons.Comment: 29 pages, 5 figures. Comments and references added, accepted for
publication in JHE
Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor
Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium
Immune-Mobilizing Monoclonal T Cell Receptors Mediate Specific and Rapid Elimination of Hepatitis B-Infected Cells
Background and Aims:
Therapies for chronic hepatitis B virus (HBV) infection are urgently needed because of viral integration, persistence of viral antigen expression, inadequate HBV‐specific immune responses, and treatment regimens that require lifelong adherence to suppress the virus. Immune mobilizing monoclonal T Cell receptors against virus (ImmTAV) molecules represent a therapeutic strategy combining an affinity‐enhanced T Cell receptor with an anti‐CD3 T Cell‐activating moiety. This bispecific fusion protein redirects T cells to specifically lyse infected cells expressing the target virus‐derived peptides presented by human leukocyte antigen (HLA).
Approach and Results:
ImmTAV molecules specific for HLA‐A*02:01‐restricted epitopes from HBV envelope, polymerase, and core antigens were engineered. The ability of ImmTAV‐Env to activate and redirect polyclonal T cells toward cells containing integrated HBV and cells infected with HBV was assessed using cytokine secretion assays and imaging‐based killing assays. Elimination of infected cells was further quantified using a modified fluorescent hybridization of viral RNA assay. Here, we demonstrate that picomolar concentrations of ImmTAV‐Env can redirect T cells from healthy and HBV‐infected donors toward hepatocellular carcinoma (HCC) cells containing integrated HBV DNA resulting in cytokine release, which could be suppressed by the addition of a corticosteroid in vitro. Importantly, ImmTAV‐Env redirection of T cells induced cytolysis of antigen‐positive HCC cells and cells infected with HBV in vitro, causing a reduction of hepatitis B e antigen and specific loss of cells expressing viral RNA.
Conclusions:
The ImmTAV platform has the potential to enable the elimination of infected cells by redirecting endogenous non‐HBV‐specific T cells, bypassing exhausted HBV‐specific T cells. This represents a promising therapeutic option in the treatment of chronic hepatitis B, with our lead candidate now entering trials
Proteomic Analysis of Rat Hypothalamus Revealed the Role of Ubiquitin–Proteasome System in the Genesis of DR or DIO
Obesity has become a global epidemic, contributing to the increasing burdens of cardiovascular disease and type 2 diabetes. However, the precise molecular mechanisms of obesity remain poorly elucidated. The hypothalamus plays a major part in regulating energy homeostasis by integrating all kinds of nutritional signals. This study investigated the hypothalamus protein profile in diet-induced obese (DIO) and diet-resistant (DR) rats using two dimensional gel electrophoresis (2-DE) combined with MALDI-TOF/TOF–MS analysis. Twenty-two proteins were identified in the hypothalamus of DIO or DR rats. These include metabolic enzymes, antioxidant proteins, proteasome related proteins, and signaling proteins, some of which are related to AMP-activated protein kinase (AMPK) signaling or mitochondrial respiration. Among these proteins, in comparison with the normal-diet group, Ubiquitin was significantly decreased in DR rats but not changed in DIO rats, while Ubiquitin carboxyl-terminal esterase L1 (UCHL-1) was decreased in DIO rats but not changed in DR rats. The expression level of Ubiquitin and UCHL-1 were further validated using Western blot analysis. Our study reveals that Ubiquitin and UCHL-1 are obesity-related factors in the hypothalamus that may play an important role in the genesis of DR or DIO by interfering with the integrated signaling network that control energy balance and feeding
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