CD4+ T Cell Count Recovery in HIV Type 1-Infected Patients Is Independent of Class of Antiretroviral Therapy

Background. In recent years, treatment options for human immunodeficiency virus type 1 (HIV-1) infection have changed from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and boosted PI-based antiretroviral drug regimens, but the impact on immunological recovery remains uncertain. Methods. During January 1996 through May 2007, all patients in the Swiss HIV Cohort were included if they received the first combination antiretroviral therapy (cART) and had known baseline CD4+ T cell counts and HIV-1 RNA values (n=3293). The mean (±SD) duration of follow-up was 26.8±20.5 months. The follow-up time was limited to the duration of the first cART. CD4+ T cell recovery was analyzed in 3 different treatment groups: nonboosted PI, NNRTI, or boosted PI. The end point was the absolute increase of CD4+ T cell count in the 3 treatment groups after the initiation of cART. Results. Two thousand five hundred ninety individuals (78.7%) initiated a nonboosted-PI regimen, 452 (13.7%) initiated an NNRTI regimen, and 251 (7.6%) initiated a boosted-PI regimen. Absolute CD4+ T cell count increases at 48 months were as follows: in the nonboosted-PI group, from 210 to 520 cells/µL; in the NNRTI group, from 220 to 475 cells/µL; and in the boosted-PI group, from 168 to 511 cells/µL. In a multivariate analysis, the treatment group did not affect the response of CD4+ T cells; however, increased age, pretreatment with nucleoside reverse-transcriptase inhibitors, serological tests positive for hepatitis C virus, Centers for Disease Control and Prevention stage C infection, lower baseline CD4+ T cell count, and lower baseline HIV-1 RNA level were risk factors for smaller increases in CD4+ T cell count. Conclusion. CD4+ T cell recovery was similar in patients receiving nonboosted PI-, NNRTI-, and boosted PI-based cAR

Characteristics, Determinants, and Clinical Relevance of CD4 T Cell Recovery to <500 Cells/µL in HIV Type 1—Infected Individuals Receiving Potent Antiretroviral Therapy

Background. The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)—infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration. Methods. Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load .05). Older age (adjusted odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21-2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28-0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19-4.81) were significantly associated with a CD4 T cell count <500 cells/µL at 5 years. The median increases in CD4 T cell count after 3-6 months of ART were smaller in incomplete responders (P < .001) and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% sensitivity and 72% specificity. Conclusion. Individuals with incomplete CD4 T cell recovery to <500 cells/µL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3-6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocyte

Cmos Programmable Time Control Circuit Design For Phased Array Uwb Ground Penetrating Radar Antenna Beamforming

Phased array radar systems employ multiple antennas to create a radar beam that can be steered electronically. By manipulating the relative phase values of feeding signals among different antennas, the effective radiation pattern of the array can be synthesized to enhance the main lobe in a desired direction while suppressing the undesired side lobes in other directions. Hence the radar scanning angles can be electronically controlled without employing the bulky mechanical gimbal structure, which can significantly reduce radar system size, weight and power consumption. In recent years, phased array technologies have received great attentions and are explored in developing many new applications, such as smart communication systems, military radars, vehicular radar, etc. Most of these systems are narrow band systems, where the phase delays are realized with narrow band phase shifter circuits. For the impulse ground penetrating radar however, its operating frequency spans an ultrawide bandwidth. Therefore the traditional phase shifters are not applicable due to their narrow band nature. To resolve the issue, in this study, a true time delay approach is explored which can precisely control time delays for the feeding pulse signals among different antennas in the array. In the design, an on chip programmable delay generator is being developed using Global Foundry 0.18 µm 7 HV high voltage CMOS process. The time delay control is realized by designing a programmable phase locked loop (PLL) circuit which can generate true time delays ranging from 100 ps (picoseconds) to 500 ps with the step size of 25 ps. The PLL oscillator\u27s frequency is programmable from 100MHz to 500MHz through two reconfigurable frequency dividers in the feedback loop. As a result, the antenna beam angle can be synthesized to change from 9.59° to 56.4° with a step of 2.75°, and the 3dB beamwidth is 10°. The power consumption of the time delay circuit is very low, where the supply voltage is 1.8V and the average current is as low as 472uA

Relationship between casting modulus and grain size in cast A356 aluminium alloys

Microstructure of Al-Si alloy castings depends most generally on melt preparation and on the cooling rate imposed by the thermal modulus of the component. In the case of Al-Si alloys, emphasis is put during melt preparation on refinement of pro-eutectic (Al) grains and on modification of the Al-Si eutectic. Thermal analysis has been used since long to check melt preparation before casting, i.e. by analysis of the cooling curve during solidification of a sample cast in an instrumented cup. The conclusions drawn from such analysis are however valid for the particular cooling conditions of the cups. It thus appeared of interest to investigate how these conclusions could extrapolate to predict microstructure in complicated cast parts showing local changes in the solidification conditions. For that purpose, thermal analysis cups and instrumented sand and die castings with different thermal moduli and thus cooling rates have been made, and the whole set of cooling curves thus recorded has been analysed. A statistical analysis of the characteristic features of the cooling curves related to grain refinement in sand and die castings allowed determining the most significant parameters and expressing the cube of grain size as a polynomial of these parameters. After introduction of a further parameter quantifying melt refining an excellent correlation, with a R2 factor of 0.99 was obtained

Clinical risk factors and atherosclerotic plaque extent to define risk for major events in patients without obstructive coronary artery disease: the long-term coronary computed tomography angiography CONFIRM registry.

AimsIn patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent.Methods and resultsPatients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS &gt;5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004).ConclusionAmong patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both

Coronary atherosclerosis scoring with semiquantitative CCTA risk scores for prediction of major adverse cardiac events: Propensity score-based analysis of diabetic and non-diabetic patients.

AIMS:We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS:Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS:A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION:Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Sex and age-specific interactions of coronary atherosclerotic plaque onset and prognosis from coronary computed tomography

Aims: The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes. Methods and results: From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64-68 years vs. 52-56 years, respectively, P 20: HR 6.71 (4.36-10.32) in women, and score 6-20: HR 1.64 (1.29-2.08); score > 20: HR 2.38 (1.73-3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6-20: HR 2.21 (1.57-3.11); score > 20: HR 6.11 (3.84-9.70) in women; score 6-20: HR 1.57 (1.19-2.09); score > 20: HR 2.25 (1.58-3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004). Conclusion: Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity.info:eu-repo/semantics/publishedVersio