1,213 research outputs found
results from a cross-sectional internet survey
Background Recent evidence suggests that the majority of HIV transmissions
among men who have sex with men (MSM) occur between steady partners. We sought
to determine factors associated with HIV transmission risks in steady
partnerships. Methods Data is from the German cross-sectional 2013 Gay Men and
AIDS survey. The study population was HIV-negative or untested men reporting a
steady partnership and at least one non-steady anal sex partner in the
previous year. Bivariate and multivariate logistic regression was used to
determine which of several independent variables best predicted both
unprotected anal intercourse (UAI) with a non-steady partner and lack of HIV
testing in the past year (high-risk outcome group). Results The study
population consisted of 1731 men. Among individuals in the outcome group (n =
271), 67 % reported UAI with a non-steady partner of unknown status and 9 %
reported UAI with a non-steady HIV-positive partner in the past 12 months; 55
% considered themselves to be at low risk for HIV acquisition. In multivariate
analyses (n = 1304), participants were statistically more likely to belong to
the outcome group if they reported UAI with their steady partner in the past
year (OR = 2.21), did not know their steady partner’s HIV status (OR = 1.98),
or agreed that condoms were disruptive during sex (OR = 3.82 (strongly agree),
OR = 2.19 (agree)). Participants were less likely to belong to the outcome
group if they were out to their primary doctor (OR = 0.54), were well-educated
about post-exposure prophylaxis (OR = 0.46), had sought information on HIV in
the past year and kept condoms in an accessible place (OR = 0.20), or believed
that insisting on condoms would lead partners to assume they were HIV-negative
(OR = 0.20). Participants in the outcome group were more likely to say they
would use HIV home tests (OR = 1.58) or pre-exposure prophylaxis (OR = 2.11).
Conclusions Based on our results, we reflect on HIV prevention measures that
should be improved in order to better target behaviors that may lead to HIV
transmission between MSM in steady relationships. In particular, we highlight
the need for multifaceted interventions focusing not only on members of the
at-risk community themselves, but on communities as a whole
ESTIMATING THE SUBJECT BY TREATMENT INTERACTION IN NON-REPLICATED CROSSOVER DIET STUDIES
Researchers in human nutrition commonly refer to the ‘consistent’ diet effect (i.e. the main effect of diet) and an ‘inconsistent’ diet effect (i.e. a subject by diet interaction). However, due to the non-replicated designs of most studies, one can only estimate the first part using ANOVA; the latter (interaction) is confounded with the residual noise. In many diet studies, it appears that subjects do respond differently to the same diet, so the subject by diet interaction may be large. In a search of over 40,000 published human nutrition studies, most using a crossover design, we found that in none was a subject by diet interaction effect estimated. For this paper, we examined LDL-cholesterol data from a non-replicated crossover study with four diets, the typical American diet, with and without added plant sterols, and a cholesterol-lowering Step-1 diet, with and without sterols. We also examined LDL-cholesterol data from a second crossover study with some replications with three diets, representing the daily supplement of 0, 1 or 2 servings of pistachio nuts. These two data sets were chosen because experience suggested that LDLcholesterol responses to diet tend to be subject-specific. The second data set, with some replication, allowed us to estimate the subject by diet interaction term in a traditional ANOVA framework. One approach to estimating an interaction effect in non-replicated studies is through the use of a multiplicative decomposition of the interaction (sometimes called AMMI―additive main effects, multiplicative interaction). In this type of analysis, residuals, formed after estimated main effects are subtracted from the data, are arrayed in a matrix with diets as columns and subjects as rows. A singular value decomposition of the matrix is performed and the first, or first and second, principal component(s) are used as estimates of the interaction, and can be tested for significance using approximate F-tests. Using the R gnm package, we found large and significant subject by diet interaction effects in both data sets; estimates of the interaction in the second data set were similar to interaction estimates from traditional ANOVA. Of an additional 26 dependent variables from the first and a third data set (the latter investigating the effect of mild alcohol consumption on blood variables), 19 had significant subject by diet interactions, based on the AMMI methodology. These results suggest that the subject by diet interaction is often important and should not be ignored when analyzing data obtained from non-replicated crossover designs―the AMMI methodology works well and is readily available in statistical software packages
Congruences modulo prime powers of Hecke eigenvalues in level
We continue the study of strong, weak, and -weak eigenforms introduced by
Chen, Kiming, and Wiese. We completely determine all systems of Hecke
eigenvalues of level modulo , showing there are finitely many. This
extends results of Hatada and can be considered as evidence for the more
general conjecture formulated by the author together with Kiming and Wiese on
finiteness of systems of Hecke eigenvalues modulo prime powers at any fixed
level. We also discuss the finiteness of systems of Hecke eigenvalues of level
modulo , reducing the question to the finiteness of a single eigenvalue.
Furthermore, we answer the question of comparing weak and -weak eigenforms
and provide the first known examples of non-weak -weak eigenforms.Comment: 28 pages; Minor revisio
Design of high-efficiency, radiation-hard, GaInP/GaAs solar cells
In recently years, Ga(0.5)In((0.5)P/GaAs cells have drawn increased attention both because of their high efficiencies and because they are well suited for space applications. They can be grown and processed as two-junction devices with roughly twice the voltage and half the current of GaAs cells. They have low temperature coefficients, and have good potential for radiation hardness. We have previously reported the effects of electron irradiation on test cells which were not optimally designed for space. From those results we estimated that an optimally designed cell could achieve 20 percent after irradiation with 10(exp 15) cm(exp -2) 1 MeV electrons. Modeling studies predicted that slightly higher efficiencies may be achievable. Record efficiencies for EOL performance of other types of cells are significantly lower. Even the best Si and InP cells have BOL efficiencies lower than the EOL efficiency we report here. Good GaAs cells have an EOL efficiency of 16 percent. The InP/Ga(0.5)In(0.5)As two-junction, two-terminal device has a BOL efficiency as high as 22.2 percent, but radiation results for these cells were limited. In this study we use the previous modeling and irradiation results to design a set of Ga(0.5)In(0.5)P/GaAs cells that will demonstrate the importance of the design parameters and result in high-efficiency devices. We report record AMO efficiencies: a BOL efficiency of 25.7 percent for a device optimized for BOL performance and two of different designs with EOL efficiencies of 19.6 percent (at 10(exp 15) cm(exp -2) 1MeV electrons). We vary the bottom-cell base doping and the top-cell thickness to show the effects of these two important design parameters. We get an unexpected result indicating that the dopant added to the bottom-cell base also increases the degradation of the top cell
Searching for faces in crowd chokepoint videos
Investigations of face identification have typically focussed on matching faces to photographic IDs. Few researchers have considered the task of searching for a face in a crowd. In Experiment 1, we created the Chokepoint Search Test to simulate real‐time search for a target. Performance on this test was poor (39% accuracy) and showed moderate associations with tests of face matching and memory. In addition, trial‐level confidence predicted accuracy, and for those participants who were previously familiar with one or more targets, higher familiarity was associated with increased accuracy. In Experiment 2, we found improvements in performance on the test when three recent images of the target, but not three social media images, were displayed during searches. Taken together, our results highlight the difficulties inherent in real‐time searching for faces, with important implications for those security personnel who carry out this task on a daily basis
The presence of prolines in the flanking region of an immunodominant HIV-2 gag epitope influences the quality and quantity of the epitope generated
Both the recognition of HIV‐infected cells and the immunogenicity of candidate CTL vaccines depend on the presentation of a peptide epitope at the cell surface, which in turn depends on intracellular antigen processing. Differential antigen processing maybe responsible for the differences in both the quality and the quantity of epitopes produced, influencing the immunodominance hierarchy of viral epitopes. Previously, we showed that the magnitude of the HIV‐2 gag‐specific T‐cell response is inversely correlated with plasma viral load, particularly when responses are directed against an epitope, 165DRFYKSLRA173, within the highly conserved Major Homology Region of gag‐p26. We also showed that the presence of three proline residues, at positions 119, 159 and 178 of gag‐p26, was significantly correlated with low viral load. Since this proline motif was also associated with stronger gag‐specific CTL responses, we investigated the impact of these prolines on proteasomal processing of the protective 165DRFYKSLRA173 epitope. Our data demonstrate that the 165DRFYKSLRA173 epitope is most efficiently processed from precursors that contain two flanking proline residues, found naturally in low viral‐load patients. Superior antigen processing and enhanced presentation may account for the link between infection with HIV‐2 encoding the “PPP‐gag” sequence and both strong gag‐specific CTL responses as well as lower viral load
The presence of prolines in the flanking region of an immunodominant HIV-2 gag epitope influences the quality and quantity of the epitope generated
Both the recognition of HIV‐infected cells and the immunogenicity of candidate CTL vaccines depend on the presentation of a peptide epitope at the cell surface, which in turn depends on intracellular antigen processing. Differential antigen processing maybe responsible for the differences in both the quality and the quantity of epitopes produced, influencing the immunodominance hierarchy of viral epitopes. Previously, we showed that the magnitude of the HIV‐2 gag‐specific T‐cell response is inversely correlated with plasma viral load, particularly when responses are directed against an epitope, 165DRFYKSLRA173, within the highly conserved Major Homology Region of gag‐p26. We also showed that the presence of three proline residues, at positions 119, 159 and 178 of gag‐p26, was significantly correlated with low viral load. Since this proline motif was also associated with stronger gag‐specific CTL responses, we investigated the impact of these prolines on proteasomal processing of the protective 165DRFYKSLRA173 epitope. Our data demonstrate that the 165DRFYKSLRA173 epitope is most efficiently processed from precursors that contain two flanking proline residues, found naturally in low viral‐load patients. Superior antigen processing and enhanced presentation may account for the link between infection with HIV‐2 encoding the “PPP‐gag” sequence and both strong gag‐specific CTL responses as well as lower viral load
Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates
BACKGROUND AND OBJECTIVES
Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates.
METHODS
We identified patients with acetylcholine receptor antibody-positive (AChR) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses. We generated recombinant monoclonal antibodies (mAbs) corresponding to the B-cell receptors of the CLL phenotype B cells and screened them for autoantigen binding.
RESULTS
A computational immune cell screen revealed a subgroup of 5/38 patients with MG and 0/21 healthy controls who displayed a CLL-like B-cell phenotype. In follow-up hematologic flow cytometry, 2 of these 5 patients were diagnosed with an MBL. An additional patient with AChR MG as a complication of manifest CLL presented at our neuromuscular clinic and was successfully treated with the anti-CD20 therapy obinutuzumab plus chlorambucil. We investigated the specificities of expanding CLL-like B-cell clones to assess a direct causal link between the 2 diseases. However, we observed no reactivity of the clones against the AChR, antigens at the neuromuscular junction, or other common autoantigens.
DISCUSSION
Our study suggests that AChR autoantibodies are produced by nonmalignant, polyclonal B cells The new anti-CD20 treatment obinutuzumab might be considered in effectively treating AChR MG.
CLASSIFICATION OF EVIDENCE
This is a single case study and provides Class IV evidence that obinutuzumab is safe to use in patients with MG
Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling
Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size
Next Generation Very Large Array Memo No. 9 Science Working Group 4: Time Domain, Fundamental Physics, and Cosmology
We report here on key science topics for the Next Generation Very Large Array in the areas of time domain, fundamental physics, and cosmology. Key science cases considered are pulsars in orbit around the Galactic Center massive black hole, Sagittarius A*, electromagnetic counterparts to gravitational waves, and astrometric cosmology. These areas all have the potential for ground-breaking and transformative discovery. Numerous other topics were discussed during the preparation of this report and some of those discussions are summarized here, as well. There is no doubt that further investigation of the science case will reveal rich and compelling opportunities
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