Unified model of short- and long-term HIV viral rebound for clinical trial planning

Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. Typically suspension of therapy is rapidly followed by rebound of viral loads to high, pre-therapy levels. Indeed, a recent study showed that approximately 90% of treatment interruption study participants show viral rebound within at most a few months of therapy suspension, but the remaining 10%, showed viral rebound some months, or years, after ART suspension. Some may even never rebound. We investigate and compare branching process models aimed at gaining insight into these viral dynamics. Specifically, we provide a theory that explains both short- and long-term viral rebounds, and post-treatment control, via a multitype branching process with time-inhomogeneous rates, validated with data from Li et al. (Li et al. 2016 AIDS 30, 343–353. (doi:10.1097/QAD.0000000000000953)). We discuss the associated biological interpretation and implications of our best-fit model. To test the effectiveness of an experimental intervention in delaying or preventing rebound, the standard practice is to suspend therapy and monitor the study participants for rebound. We close with a discussion of an important application of our modelling in the design of such clinical trials.     

Molecular cloning of the cDNA encoding a murine sialic acid-specific 9-O-acetylesterase and RNA expression in cells of hematopoietic and non-hematopoietic origin

We describe the isolation of a cDNA encoding a murine sialic acid-specific 9-O-acetylesterase as well as its expression pattern in cells of both hematopoietic and non-hematopoietic origin. This enzyme catalyzes the removal of O-acetyl ester groups from position 9 of the parent sialic acid N-acetylneuraminic acid. The cDNA is 2105 nt in length and encodes a protein of 541 amino acids with a predicted molecular weight of 61 kDa, not including oligosaccharides linked to eight potential N-glycosylation sites. The cDNA encoding the acetylesterase displays a widespread distribution in various cell lines and tissues. Expression studies of B lineage cell lines and primary fetal liver cells revealed a developmentally regulated expression pattern in cells of hematopoietic origin. Given the importance of 9-O-acetylation of sialic acids, the cloning of the cDNA encoding a sialic acid-specific 9-O-acetylesterase will be helpful in understanding further the regulation of this post-translational modification and the biological consequences thereof.     

The Minnesota Substance Abuse Problems Scale. Psychometric analysis and validation in a clinical population

Quantitative determination of viral load using nucleic acid amplification techniques represents the most accurate prognostic marker for human immunodeficiency virus type 1 (HIV-1) infection, independently of CD4+ cell count. Overall, the different methods for HIV-1 RNA determination (RT-PCR, nucleic acid sequence-based amplification, branched DNA) show a good reproducibility (0.5 log), however for low copy numbers and in HIV-1-infected children the variability may exceed 0.7 log. In non-HIV-1 subtype B infections the copy number is underestimated. While serology permits an accurate follow-up of hepatitis B virus (HBV) infection, HBV DNA quantification is used for monitoring of antiviral therapy, determination of infectiosity and in combination with serological markers for the resolution of unusual profiles, i.e. isolated anti-HBc reactivity. The prognostic relevance of hepatitis C virus (HCV) RNA determination is of limited value for the long-term prognosis of chronic hepatitis C, however the viral load may predict the outcome of antiviral therapy. Genetic diversity represents a challenge for HCV RNA quantification.     

Stability of validity indices through test score ranges.

Effects of correction for restriction in range and variability of validity evidence throughout the predictor score range were examined in a sample of 16,230 inexperienced life insurance agents. The predictor variable was the Aptitude Index Battery (a biographical inventory) and the criterion was 1-year objective sales production. Data displayed nonlinearity and heteroscedasticity. Although variations in the validity coefficients and the slopes within the restricted samples were observed, these were generally accounted for by sampling error. When analyzed with linear regression techniques, data showed stronger relationships between the predictor and criterion at the upper score range; however, when analyzed with techniques appropriate for nonlinear, heteroscedastic data, validity evidence indicated better predictability at lower score ranges. Increasing the truncation of the distribution yielded increasingly overestimated slopes and corrected correlations. Influences of nonlinearity and heteroscedasticity and implications for the use of the direct restriction of range correction formula are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reports of the childhood home environment in early-onset dysthymia and episodic major depression.

This study addressed 2 questions: (a) is early-onset dysthymia associated with reports of a disturbed childhood home environment; and (b) can adverse early experiences account, at least in part, for the differing clinical presentations of dysthymia and major depression? Participants included 97 outpatients with early-onset dysthymia, 45 outpatients with episodic major depression, and 45 normal controls. The early home environment was assessed blind to diagnosis using both interview and self-report measures. Early-onset dysthymia patients reported significantly more physical and sexual abuse and poorer relationships with both parents than normal controls. In addition, patients with dysthymia reported having received significantly poorer parenting than those with episodic major depression. The results could not be accounted for by mood state effects, comorbidity with borderline and antisocial personality disorder, or comorbid major depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Broadband video switching

A broadband 64×16 space-switching approach and its applicability to large-scale broadband switching systems are described. The design uses a technique that prevents the parasitic capacitances from reducing the switching speed. The switching system was implemented in 3-μm CMOS VLSI and operated in excess of 150 Mb/s. Computer simulation indicates a 1-Gb/s potential with a 1-μm CMOS implementation     

Electrical impedance of superconductor/polymer composites

Electrical impedance measurements were carried out on high-T _c superconducting ceramic/polymer composite materials, in which superconducting particles are embedded in a polymer matrix. The results for the impedance magnitude and phase angle versus frequency (1 kHz-1 MHz), temperature (50–290 K) and volume percentage of superconductor (0–70%) are presented. The results reveal that the a.c. electrical properties of the new composite materials go through a large change at volume percentage of powder filler around 40%, which indicates that particle-particle contacts are partially formed. Far below this composition the composite is an insulator, and above this composition the composite behaves as a semiconductor. No marked transition in impedance and phase angle was observed when the material went through the superconducting transition temperature.     

Programmable binary phase-only optical device based on ferroelectric liquid crystal SLM

The performance is reported of a programmable, two-level, phase-only device based on a commercially available 128*128 pixellated, ferroelectric liquid crystal spatial light modulator (SLM). Near diffraction limited performance is achieved results for a Dammann grating are comparable to those obtainable with fixed components.<>     

Modelling of aircraft manufacturing cost at the concept stage

The work presented is concerned with the estimation of manufacturing cost at the concept design stage, when little technical information is readily available. The work focuses on the nose cowl sections of a wide range of engine nacelles built at Bombardier Aerospace Shorts of Belfast. A core methodology is presented that: defines manufacturing cost elements that are prominent; utilises technical parameters that are highly influential in generating those costs; establishes the linkage between these two; and builds the associated cost estimating relations into models. The methodology is readily adapted to deal with both the early and more mature conceptual design phases, which thereby highlights the generic, flexible and fundamental nature of the method. The early concept cost model simplifies cost as a cumulative element that can be estimated using higher level complexity ratings, while the mature concept cost model breaks manufacturing cost down into a number of constituents that are each driven by their own specific drivers. Both methodologies have an average error of less that ten percent when correlated with actual findings, thus achieving an acceptable level of accuracy. By way of validity and application, the research is firmly based on industrial case studies and practice and addresses the integration of design and manufacture through cost. The main contribution of the paper is the cost modelling methodology. The elemental modelling of the cost breakdown structure through materials, part fabrication, assembly and their associated drivers is relevant to the analytical design procedure, as it utilises design definition and complexity that is understood by engineers.     

Opioids and rate of positively reinforced behavior: II. Antagonism by β-funaltrexamine.

Lever pressing by rats (Rattus norvegicus) was maintained under a fixed-ratio 20 schedule of food presentation. Response rate-decreasing effects of the opioid compounds fentanyl, U50,488, butorphanol, and nalorphine were examined alone and in combination with the irreversible, μ-selective opioid antagonist β-funaltrexamine (β-FNA) antagonized the rate-decreasingly effects of both fentanyl and butorphanol. β-FNA was more potent and the duration of antagonism was greater, against butorphanol than against fentanyl. β-FNA also antagonized the effects of the higher nalorphine doses: however, lower doses of nalorphine, which were without effect alone, decreased response rates in the presence of β-FNA. The dose–effect curve for U50,488 was shifted leftward in the presence of β-FNA. These data suggest that, β-FNA may be useful in assessing μ-receptor activity related to the effects of opioids on rate of operant behavior and the efficacy with which opioids produce these effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)