Miracle-dz/UniFAR-FTUs huggingface dataset:
Variations in adrenocortical responsiveness during severe bacterial infections. Unrecognized adrenocortical insufficiency in severe bacterial infections.

Plasma cortisol levels and their response to . 25 mg synthetic A.C. T.H. (Cortrosyn) were studied in 26 septic patients. Four (15.4%) of these patients appeared to have greatly increased adrenocortical activity with plasma cortisol levels averaging 65.4 +/- 14.8 microgram/dl (normal = 8-18 microgram/dl. All four of these patients were agonal and died within five days. Seventeen (65.4%) of these 26 patients appeared to have an appropriate adrenocortical response to severe infection in that their plasma cortisol levels increased (averaging 19.2 +/- 6.0 microngram/dl) following synthetic A.C. T.H. The remaining five patients, who constituted 19.2% of the 26 patients studied, appeared to have some impairment of adrenocortical function. In spite of severe bacterial infections and no history to support Addison's disease, their plasma cortisol levels (averaging 13.8 +/- 3.3 microgram/dl) were not increased above normal and their response to Cortrosyn was much less than would be expected; the increase in plasma cortisol levels in these patients following the synthetic A.C. T.H. averaged 1.1 +/- 3.6 microgram/dl. It is reemphasized that patients with severe sepsis who are not responding adequately to standard therapy should be suspected of having adrenocortical insufficiency and treated accordingly.
Three‐dimensional MRI of coronary arteries using an intravascular contrast agent

To assess the effectiveness of an intravascular contrast agent, MS‐325, for enhancing the vascular signal in coronary MR angiograms, six minipigs were studied using a three‐dimensional, gradient‐echo sequence with retrospective respiratory gating. To suppress the myocardial signal, preparatory RF pulses were applied before data acquisition. With the administration of MS‐325, the blood signal‐to‐noise ratio increased by 97‐276%, depending on the region of interest in which the blood signal was measured and the precontrast imaging sequence structures. The blood/myocardium contrast‐to‐noise ratio also significantly increased. High‐resolution images (0.58 × 0.58 × 1 mm3) obtained from postmortem pig hearts demonstrated the potential delineation of coronary arteries with MS‐325. In conclusion, this study supports further evaluation of the utility of MS‐325 in improving coronary MR angiography in humans.
Probing vocal fold fibroblast response to hyaluronan in 3D contexts

A number of treatments are being investigated for vocal fold (VF) scar, including designer implants. The aim of the present study was to validate a 3D model system for probing the effects of various bioactive moieties on VF fibroblast (VFF) behavior toward rational implant design. We selected poly(ethylene glycol) diacrylate (PEGDA) hydrogels as our base‐scaffold due to their broadly tunable material properties. However, since cells encapsulated in PEGDA hydrogels are generally forced to take on rounded/stellate morphologies, validation of PEGDA gels as a 3D VFF model system required that the present work directly parallel previous studies involving more permissive scaffolds. We therefore chose to focus on hyaluronan (HA), a polysaccharide that has been a particular focus of the VF community. Toward this end, porcine VFFs were encapsulated in PEGDA hydrogels containing consistent levels of high M w HA (${\rm HA}_{{\rm H}{M}_{\rm W} } $), intermediate Mw HA (${\rm HA}_{{\rm I}{M}_{\rm W} } $), or the control polysaccharide, alginate, and cultured for 7 and 21 days. ${\rm HA}_{{\rm H}{M}_{\rm W} } $ promoted sustained increases in active ERK1/2 relative to ${\rm HA}_{{\rm I}{M}_{\rm W} } $ . Furthermore, VFFs in ${\rm HA}_{{\rm I}{M}_{\rm W} } $ gels displayed a more myofibroblast‐like phenotype, higher elastin production, and greater protein kinase C (PkC) levels at day 21 than VFFs in ${\rm HA}_{{\rm H}{M}_{\rm W} } $ and alginate gels. The present results are in agreement with a previous 3D study of VFF responses to ${\rm HA}_{{\rm I}{M}_{\rm W} } $ relative to alginate in collagen‐based scaffolds permissive of cell elongation, indicating that PEGDA hydrogels may serve as an effective 3D model system for probing at least certain aspects of VFF behavior. Biotechnol. Bioeng. 2009; 104: 821–831 © 2009 Wiley Periodicals, Inc.
Using record linkage and manual follow-up to evaluate the Victorian maternal serum screening quadruple test for Down's syndrome, trisomy 18 and neural tube defects

Objectives: The Genetic Health Services Victoria maternal serum screening (MSS) quadruple test has been available to pregnant women in Victoria since 1996. The objectives of this study were to follow up the pregnancies screened by MSS between July 1998 and June 2000 and to determine the performance characteristics of the test for Down's syndrome, trisomy 18 and neural tube defects (NTDs). Methods: MSS results were matched to pregnancy outcome information from the Perinatal Data Collection Unit and Birth Defects Register, using automated probabilistic record linkage. For unmatched pregnancies, manual follow-up was carried out by contacting referring doctors and hospitals, resulting in a very high follow-up rate of 99.2% (18,989/19,143). Results: The sensitivity of MSS for Down's syndrome was 85% (23/27–95%CI 72–99%) with a falsepositive rate (FPR) of 6.8% (risk threshold ≥ 1 in 250). While using a fixed 5% FPR, the sensitivity for Down's syndrome was slightly lower (78%). The sensitivity for trisomy 18 was 44% (4/9 – 95% CI 12–77%) with a FPR of 0.5% (risk threshold of ≥ 1 in 200). 11 of the 15 (73 – 95%CI 51–97%) cases of open NTDs were detected from screening, with a 1% FPR (risk threshold alpha-fetoprotein [AFP] ≥2.5 MoM). All cases of anencephaly had increased AFP levels. Conclusion: Probabilistic record linkage and manual follow-up is an efficient method for ascertainment of pregnancy outcomes, with a higher follow-up rate than that reported in similar studies. MSS should remain an available option for all pregnant women in Victoria, with test characteristics comparable with other recent reports of the quadruple test.
Pulmonary complications following lung resection: a comprehensive analysis of incidence and possible risk factors.

STUDY OBJECTIVES To assess the incidence and clinical implications of postoperative pulmonary complications (PPCs) after lung resection, and to identify possible associated risk factors. DESIGN Retrospective study. SETTING An 885-bed teaching hospital. PATIENTS AND METHODS We reviewed all patients undergoing lung resection during a 3-year period. The following information was recorded: preoperative assessment (including pulmonary function tests), clinical parameters, and intraoperative and postoperative events. Pulmonary complications were noted according to a precise definition. The risk of PPCs associated with selected factors was evaluated using multiple logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Two hundred sixty-six patients were studied (87 after pneumonectomy, 142 after lobectomy, and 37 after wedge resection). Sixty-eight patients (25%) experienced PPCs, and 20 patients (7.5%) died during the 30 days following the surgical procedure. An American Society of Anesthesiology (ASA) score > or= 3 (OR, 2.11; 95% CI, 1.07 to 4.16; p < 0.02), an operating time > 80 min (OR, 2.08; 95% CI, 1.09 to 3.97; p < 0.02), and the need for postoperative mechanical ventilation > 48 min (OR, 1.96; 95% CI, 1.02 to 3.75; p < 0.04) were independent factors associated with the development of PPCs, which was, in turn, associated with an increased mortality rate and the length of ICU or surgical ward stay. CONCLUSIONS Our results confirm the relevance of the ASA score in a selected population and stress the importance of the length of the surgical procedure and the need for postoperative mechanical ventilation in the development of PPCs. In addition, preoperative pulmonary function tests do not appear to contribute to the identification of high-risk patients.
Pricing via Quantization in Stochastic Volatility Models

In this paper we apply a new methodology based on quantization to price options in stochastic volatility models. This method can be applied to any model for which an Euler scheme is available for the underlying process and it allows for pricing vanillas, as well as exotics, thanks to the knowledge of the transition probabilities for the discretized stock process. We apply the methodology to some celebrated stochastic volatility models, including the Stein and Stein (1991) model and the SABR model introduced in Hagan and Woodward (2002). A numerical exercise shows that the pricing of vanillas turns out to be accurate; in addition, when applied to some exotics like equity-volatility options, the quantization-based method overperforms by far the Monte Carlo simulation.
How Social Status Shapes Person Perception and Evaluation: A Social Neuroscience Perspective

Inferring the relative rank (i.e., status) of others is essential to navigating social hierarchies. A survey of the expanding social psychological and neuroscience literatures on status reveals a diversity of focuses (e.g., perceiver vs. agent), operationalizations (e.g., status as dominance vs. wealth), and methodologies (e.g., behavioral, neuroscientific). Accommodating this burgeoning literature on status in person perception, the present review offers a novel social neuroscientific framework that integrates existing work with theoretical clarity. This framework distinguishes between five key concepts: (1) strategic pathways to status acquisition for agents, (2) status antecedents (i.e., perceptual and knowledge-based cues that confer status rank), (3) status dimensions (i.e., domains in which an individual may be ranked, such as wealth), (4) status level (i.e., one’s rank along a given dimension), and (5) the relative importance of a given status dimension, dependent on perceiver and context characteristics. Against the backdrop of this framework, we review multiple dimensions of status in the nonhuman and human primate literatures. We then review the behavioral and neuroscientific literatures on the consequences of perceived status for attention and evaluation. Finally, after proposing a social neuroscience framework, we highlight innovative directions for future social status research in social psychology and neuroscience.
Format of the RSVP DCLASS Object

Resource Reservation Protocol (RSVP) signaling may be used to request Quality of Service (QoS) services and enhance the manageability of application traffic's QoS in a differentiated service (diff-serv or DS) network. When using RSVP with DS networks it is useful to be able to carry carry Differentiated Services Code Points (DSCPs) in RSVP message objects. One example of this is the use of RSVP to arrange for the marking of packets with a particular DSCP upstream from the DS network's ingress point, at the sender or at a previous network's egress router.
Mutations in TNFRSF13B Encoding TACI Are Associated With Common Variable Immunodeficiency in Humans

> Purpose of the Studies. To search for mutations of TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor; also TNFRSF13B) in patients with common variable immunodeficiency (CVID) and immunoglobulin A deficiency (IGAD). Study Populations. Salzer et al screened 162 unrelated individuals with CVID. Castigli et al studied 19 unrelated individuals with CVID and 16 with IGAD. Healthy individuals (100 and 50, respectively) served as controls. Methods. Genomic DNA from patients was subjected to reverse transcription and polymerase chain reaction sequencing analysis of the 5 exons of the gene encoding TACI. Binding of mutant TACI to ligands and stimulation of immunoglobulin production in vitro with TACI agonists in patients was also studied. Results. Salzer et al identified 13 individuals with CVID who had mutations in TACI. Castigli et al identified 4 individuals with CVID and 1 with IGAD and TACI mutations. None of the 150 controls studied had any of the identified TACI mutations. Interestingly, TACI mutations could cause disease in both the heterozygous and homozygous conditions. Patients’ cells had diminished binding to TACI ligands and showed diminished responses (immunoglobulin production) to TACI agonists in vitro. The clinical characteristics of the patients included hypogammaglobulinemia and impaired antibody responses, recurrent bacterial sinopulmonary infections, autoimmune disease (anemia, thyroiditis, positive antinuclear antibody), lymphoproliferative disease, and malignancy (B-cell lymphoma, gastric carcinoma). Conclusions. Approximately 8% to 20% of patients with severe combined immunodeficiency or IGAD may have heterozygous or homozygous mutation in TACI. This genetic alteration should be sought in patients with these disorders. Reviewer Comments. CVID and IGAD are among the most prevalent humoral immunodeficiencies at all ages. These studies represent important descriptions of defined mutations in patients with CVID and IGAD occurring in a significant fraction of these patients in 2 relatively genetically disparate populations. The ability to clearly define the underlying cause of disease in these patients will immediately lead to greater accuracy and confidence in diagnosis, earlier and more aggressive therapy, and, hopefully, improved outcomes.
Mixtures of Varying Coefficient Models for Longitudinal Data with Discrete or Continuous Nonignorable Dropout

Summary The analysis of longitudinal repeated measures data is frequently complicated by missing data due to informative dropout. We describe a mixture model for joint distribution for longitudinal repeated measures, where the dropout distribution may be continuous and the dependence between response and dropout is semiparametric. Specifically, we assume that responses follow a varying coefficient random effects model conditional on dropout time, where the regression coefficients depend on dropout time through unspecified nonparametric functions that are estimated using step functions when dropout time is discrete (e.g., for panel data) and using smoothing splines when dropout time is continuous. Inference under the proposed semiparametric model is hence more robust than the parametric conditional linear model. The unconditional distribution of the repeated measures is a mixture over the dropout distribution. We show that estimation in the semiparametric varying coefficient mixture model can proceed by fitting a parametric mixed effects model and can be carried out on standard software platforms such as SAS. The model is used to analyze data from a recent AIDS clinical trial and its performance is evaluated using simulations.
Effect of preoperative P2Y12 and thrombin platelet receptor inhibition on bleeding after cardiac surgery.

BACKGROUND Drugs that act on the platelet P2Y12 receptor are responsible for postoperative bleeding in cardiac surgery. However, protease-activated receptor (PAR) that reacts to thrombin stimulation might still be active in patients treated with P2Y12 inhibitors. Preoperative platelet function testing could possibly guide the timing of surgery. We investigated the association between P2Y12 receptor and PAR inhibition and bleeding after cardiac surgery. METHODS A retrospective cohort study of 361 patients undergoing cardiac surgery and treated with P2Y12 anti-platelet agents was undertaken. All patients received a preoperative multiplate electrode aggregometry testing of platelet P2Y12 receptor activity (ADPtest) and PAR reactivity with thrombin receptor-activating peptide (TRAP) stimulation. ADPtest and TRAPtest data measured before surgery were analysed for association with postoperative bleeding (ml per 12 h) and severe postoperative bleeding. RESULTS Both the ADPtest and the TRAPtest were significantly (P=0.001) associated with postoperative bleeding. A threshold of 22 U for the ADPtest yielded a negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 20%, and a threshold of 75 U for the TRAPtest yielded an NPV of 95% and a PPV of 23%. In the subgroup of patients with ADPtest <22 U, TRAPtest ≥75 U was not associated with severe bleeding (NPV of 100% and PPV of 37%). CONCLUSIONS In patients taking P2Y12 receptor inhibitors, residual platelet reactivity to thrombin stimulation limits the risk of severe postoperative bleeding.
Conserved Sequence Box II Directs Transcription Termination and Primer Formation in Mitochondria*

The human mitochondrial transcription machinery generates the RNA primers needed for initiation of heavy strand DNA synthesis. Most DNA replication events from the heavy strand origin are prematurely terminated, forming a persistent RNA-DNA hybrid, which remains annealed to the parental DNA strand. This triple-stranded structure is called the D-loop and encompasses the conserved sequence box II, a DNA element required for proper primer formation. We here use a purified recombinant mitochondrial transcription system and demonstrate that conserved sequence box II is a sequence-dependent transcription termination element in vitro. Transcription from the light strand promoter is prematurely terminated at positions 300-282 in the mitochondrial genome, which coincide with the major RNA-DNA transition points in the D-loop of human mitochondria. Based on our findings, we propose a model for primer formation at the origin of heavy strand DNA replication.
Three-dimensional tree simulation considering interfaces with various angles of inclination to electric force line

We previously carried out a three-dimensional (3D) tree simulation of a composite system with an interface perpendicular or parallel to the electric force line based on a dielectric breakdown model considering the growth probability. It was found that an interface perpendicular to the electric force line exhibits a positive barrier effect and that an interface parallel to the electric force line exhibits a negative barrier effect. In this study, we carried out a 3D tree simulation that considers interfaces having various angles of inclination to the electric force line, for which different barrier effects were observed. Furthermore, the simulated tree with interfaces having various angles of inclination either creeps on the barrier, penetrates the barrier or develops along the edge of the barrier.
Dihydroberberine exhibits synergistic effects with sunitinib on NSCLC NCI‐H460 cells by repressing MAP kinase pathways and inflammatory mediators

Highly effective and attenuated dose schedules are good regimens for drug research and development. Combination chemotherapy is a good strategy in cancer therapy. We evaluated the antitumour effects of dihydroberberine combined with sunitinib (DCS) on the human non‐small cell lung cancer cell lines (NSCLC), A549, NCI‐H460, and NCI‐H1299 in vitro and in vivo. DCS showed synergic effects on NCI‐H460 cell proliferation, colony formation and transplantable tumour growth, which suggested dihydroberberine increases the sensitivity of lung carcinoma to sunitinib. Further studies indicated that DCS down‐regulated phosphorylation of JNK, p38, and NF‐κB in NCI‐H460 cells and tumours and suppressed the IκB and COX‐2 expression. In addition, DCS reduced the secretion of the pro‐inflammatory cytokine, interleukin‐1 (IL‐1), in tumours. Inhibition of p38 activation by DCS was a likely contributing factor in IL‐1 and COX‐2 down‐regulation. Consistent with these results, a genomewide microarray analysis found that DCS induced the expression of cell cycle signal molecules that are known to be affected by JNK and p38. The change of cell cycle, in turn, led to down‐regulation of JNK and p38, and further reduced IL‐1 secretion. Collectively, these findings highlight potential molecular mechanisms of DCS chemotherapeutic activity and suggest that DCS is an efficacious strategy in NSCLC therapy.
Adolescent Life-Event Stress in Boys Is Associated with Elevated IL-6 and Hepcidin but Not Hypoferremia

Objective: The link between stress-related increases in inflammatory markers, hepcidin, and iron status are poorly understood, especially in developing countries like India. The aim of the study was to examine the relationship between adolescent life-event stress (ALES), inflammatory markers, and its association with hepcidin and biomarkers of iron status among adolescent boys. Methods: Data pertaining to a subsample of 145 participants from a cross-sectional, school-based study recruiting 370 adolescent boys aged 15–19 years, from 5 schools in Hyderabad, India, were analyzed. Stress was assessed using the ALES scale, psychological distress by the General Health Questionnaire-2 (GHQ-12), and approach and avoidance coping using the Coping Strategies Scale. Biomarkers of iron and concentrations of other micronutrients, hepcidin, IL-6 and C-reactive protein (CRP) in plasma were analyzed. Data were subjected to regression, path analyses, and analysis of covariance (ANCOVA). Results: ALES was a significant predictor of interleukin (IL)-6 (β = 0.196, p = 0.012), CRP (β = 0.217, p = 0.010), and log hepcidin (β = 0.228, p = 0.006). Hepcidin correlated significantly (p < 0.001) with IL-6 (r = 0.344) and CRP (r = 0.370) but not with the biomarkers of iron status. Path analysis showed that the model had an acceptable fit, with a root mean square error of approximation of 0.019, 90% confidence interval (CI) of 0.00–0.074, comparative fit index of 0.988, chi-square p = 0.393, and chi-square/df of 1.053. Conclusions: Adolescent life-event stress is associated with elevated IL-6 and hepcidin concentration but not hypoferremia. These findings may help in iron supplementation programs for tackling anemia.
Visceral leishmaniasis in congenic mice of susceptible and resistant phenotypes: immunosuppression by adherent spleen cells

Visceral leishmaniasis is one of several parasitic diseases of humans characterized by immune suppression. A murine model of disseminated leishmaniasis utilizing inbred strains of specific genetic constitution was used to study the mechanisms of immunosuppression elicited during the course of infection. Resistant (Lshr) and susceptible (Lshs) strains of mice were challenged with amastigotes of Leishmania donovani and evaluated as to immune status at intervals between 2 and 40 weeks after challenge. The proliferative responses of splenic lymphocytes to T-cell mitogens, a B-cell mitogen, and parasite antigens were measured to evaluate the relative immune status of parasitized mice and noninfected control mice. Lymphocytes from resistant C3Heb/FeJ (C3H) mice responded normally to concanavalin A and phytohemagglutinin throughout the course of infection. Parasite antigen responses appeared 2 weeks after challenge of C3H mice and remained vigorous for periods up to 6 months. In contrast, immune suppression during infection was profound in both the curing (C57B1/10) and noncuring (B10.D2) phenotypes of Lshs congenic mice. Both Lshs strains developed severe infection as evidenced by high parasite burdens in the liver and spleen 4 to 5 weeks after challenge; splenic lymphocytes taken from these mice between 2 and 8 weeks became increasingly unresponsive to the T-cell mitogens as well as to parasite antigens. The noncuring B10.D2 mice which suffered chronic infection continued to be suppressed for as long as 40 weeks. C57B1/10 (curing) mice, in contrast, cleared infection between 12 and 16 weeks. After spontaneous recovery or elimination of parasites by antimonial drug therapy, the response of spleen cells to T-cell mitogens or parasite antigens were restored to normal. The spleen cells from the Lshs strains of mice obtained during the height of infection suppressed the proliferative responses of spleen cells from their uninfected counterparts upon cocultivation in vitro. Removal of adherent cells from the suppressive spleen cell populations restored normal mitogen responses. On the basis of adherence characteristics, phagocytosis, and morphology, the suppressor was identified as a macrophage population which appears to be responsible for a nonspecific immunosuppression of Lshs mice with significant parasite burdens of L. donovani.