Apoptotic depletion of CD4<SUP>+</SUP> T cells in idiopathic CD4<SUP>+</SUP> T lymphocytopenia

Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients, The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8+ T cells predominantly in those individuals with marked depletion of both CD4+ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors

All-cause mortality after major gastrointestinal bleeding among patients receiving direct oral anticoagulants: a protocol for a systematic review and meta-analysis.

BACKGROUND Gastrointestinal (GI) bleeding represents the single most frequent site of anticoagulant-related bleeding. Adverse outcomes after major GI bleeding including mortality are not well characterized and, as a result, may be underappreciated in clinical practice. We aim to conduct a systematic review and meta-analysis of the risk for 30-day all-cause mortality after major GI bleeding among patients receiving DOACs. METHODS Electronic databases including MEDLINE, EMBASE, and Cochrane CENTRAL will be systematically searched to identify randomized controlled trials and prospective and retrospective cohort studies reporting 30-day all-cause mortality in adults with DOAC-related major GI bleeding. At least two investigators will independently perform study selection, risk of bias assessment, and data extraction. The proportion of deaths following a major GI event relative to the number of major GI bleeding events will be calculated for each individual study, and results across studies will be pooled using random-effects meta-analysis. We will assess risk of bias using criteria proposed by the GRADE group for prognostic studies. DISCUSSION The findings of this systematic review and meta-analysis will provide clinicians and patients with estimates of mortality after the most common major bleeding event to support shared decision making about anticoagulation management. TRIAL REGISTRATION PROSPERO CRD42022295815

Unidentified EGRET Sources and the Extragalactic Gamma-Ray Background

The large majority of EGRET point sources remain to this day without an identified low-energy counterpart. Whatever the nature of the EGRET unidentified sources, faint unresolved objects of the same class must have a contribution to the diffuse gamma-ray background: if most unidentified objects are extragalactic, faint unresolved sources of the same class contribute to the background, as a distinct extragalactic population; on the other hand, if most unidentified sources are Galactic, their counterparts in external galaxies will contribute to the unresolved emission from these systems. Understanding this component of the gamma-ray background, along with other guaranteed contributions from known sources, is essential in any attempt to use gamma-ray observations to constrain exotic high-energy physics. Here, we follow an empirical approach to estimate whether a potential contribution of unidentified sources to the extragalactic gamma-ray background is likely to be important, and we find that it is. Additionally, we comment on how the anticipated GLAST measurement of the diffuse gamma-ray background will change, depending on the nature of the majority of these sources.Comment: 6 pages, 3 figures, to appear in proceedings of "The Multi-Messenger Approach to High Energy Gamma-Ray Sources", Barcelona, 4-7 July 2006; comments welcom

Analysis and Modification of Amorphous and Partially-Crystalline Thin Films

Thin films of light atomic weight elements in amorphous, partially-crystalline, or crystalline forms have applications in a broad range of technologies. For example, amorphous tetrahedral carbon (a-tC) and polymeric thin films impact electronic materials technology as electron- and light-emitting device elements, respectively. A lack of crystallinity introduces complexity in the experimental and theoretical characterization of these materials but is not necessarily a limiting factor in their performance. While the growth process is clearly a major factor governing the physical properties of a film, interactions with the substrate are also important, so surface and interface analysis provides an important complement to bulk measurements. This paper focuses on several approaches in the characterization and modification of thin films made possible by recent experimental advances. The structural and electronic properties of two model systems are considered as examples: a-tC thin films grown by pulsed laser deposition (PLD) and polyaniline thin films grown by vapor deposition. First, scanning probe microscopies and X-ray scattering are used to investigate the structural aspects of a-tC films as a function of PLD growth conditions. The possible connection of nanoscale surface modification and characterization with electron emission properties will be discussed. Second, the results of inelastic scattering spectroscopy and other surface techniques will be discussed to obtain information on both interfacial aspects of the growth of polyaniline thin films and microscopic and macroscopic aspects of electrical conductivity upon doping. Comparisons will be made with other studies that address properties of analogous crystalline systems as appropriate. A brief assessment of the broader problem of analyzing these systems will be given

Children's spontaneous correction of false beliefs in a conversation partner.

Preschool children were tested for their ability to vary the verbal information they offered regarding an object's location depending on whether the person searching for that object was likely to infer or misinfer its location. Older children (mean age: 5 years 3 months) offered information in a selective fashion: If the location of the hidden object could be readily inferred by their conversation partner, they indicated its location only when explicitly asked but if its location was likely to be misinferred, they often indicated that location prior to being explicitly asked. The response pattern of younger children (mean age: 3 years 6 months) was less conclusive. A relatively large number of younger children took matters "into their own hands" and immediately grasped for the concealed object, irrespective of whether its location could be readily inferred. However, the reactions of the remaining 3-year-olds suggest that even at this age children may be sensitive to the likely beliefs of their conversation partner. © 1999 The International Society for the Study of Behavioural Development

Microstructural evolutions in converting epitaxial Tl2Ba2CaCu2Ox thin films to epitaxial HgBa2CaCu2O6+delta thin films

Superconducting HgBa2CaCu2O6+delta (Hg-1212) thin films were obtained from Tl2Ba2CaCu2Ox (Tl-2212) precursor films using a cation-exchange process. In this process, Tl cations on the precursor lattice were thermally excited and then replaced with Hg cations. The mechanism of such an atomic perturbation process has presented an interesting topic in material research. This work investigated the evolution of the crystalline structure and surface morphology of the film during such a conversion. It has been found that the Hg-1212 films may inherit epitaxy and surface morphology from their Tl2Ba2CaCu2Ox precursor films at the low perturbation energy limit. Although the c-axis lattice constant was reduced from 1.48 rim. for Tl-2212 to 1.27 nm for Hg-1212 during the cation exchange, the in-plane texture of the film remains. The inverse conversion from Hg-1212 to Tl-2212 has also been investigated. Hg-1212 is found to be energetically preferred so that a perturbation above a threshold is required to convert it back to Tl-2212. (C) 2003 American Institute of Physics. [DOI: 10.1063/1.1529305]

Annihilation vs. Decay: Constraining dark matter properties from a gamma-ray detection

Most proposed dark matter candidates are stable and are produced thermally in the early Universe. However, there is also the possibility of unstable (but long-lived) dark matter, produced thermally or otherwise. We propose a strategy to distinguish between dark matter annihilation and/or decay in the case that a clear signal is detected in gamma-ray observations of Milky Way dwarf spheroidal galaxies with gamma-ray experiments. The sole measurement of the energy spectrum of an indirect signal would render the discrimination between these cases impossible. We show that by examining the dependence of the intensity and energy spectrum on the angular distribution of the emission, the origin could be identified as decay, annihilation, or both. In addition, once the type of signal is established, we show how these measurements could help to extract information about the dark matter properties, including mass, annihilation cross section, lifetime, dominant annihilation and decay channels, and the presence of substructure. Although an application of the approach presented here would likely be feasible with current experiments only for very optimistic dark matter scenarios, the improved sensitivity of upcoming experiments could enable this technique to be used to study a wider range of dark matter models.Comment: 29 pp, 8 figs; replaced to match published version (minor changes and some new references

Attitudes towards medication non-adherence in elderly kidney transplant patients: A Q methodology study

Background. Non-adherence to the post-transplant regime is a common problem in kidney transplant patients and may lead to rejection or even graft failure. This study investigated attitudes towards the post-transplant regime of immunosuppressive medication among the ever growing population of elderly kidney recipients.Methods. Q methodology was used to explore attitude profiles. Participants (> 65 years) were asked to rank-order opinion statements on issues associated with (non-)adherence. The rankings were subject to by-person factor analysis, and the resulting factors were interpreted and described as attitudes.Results. Twenty-six elderly renal transplant recipients participated in the study. All passed the Mini-Mental

Automatic differentiation for gradient-based optimization of radiatively heated microelectronics manufacturing equipment

Automatic differentiation is applied to the optimal design of microelectronic manufacturing equipment. The performance of nonlinear, least-squares optimization methods is compared between numerical and analytical gradient approaches. The optimization calculations are performed by running large finite-element codes in an object-oriented optimization environment. The Adifor automatic differentiation tool is used to generate analytic derivatives for the finite-element codes. The performance results support previous observations that automatic differentiation becomes beneficial as the number of optimization parameters increases. The increase in speed, relative to numerical differences, has a limited value and results are reported for two different analysis codes