Estimating Patterns of CD4+ Lymphocyte Decline Using Data from a Prevalent Cohort of HIV Infected Individuals

In natural history studies of chronic disease, it is of interest to understand the evolution of key variables that measure aspects of disease progression. This is particularly true for immunological variables in persons infected with the Human Immunodeficiency Virus (HIV). The natural timescale for such studies is time since infection. However, most data available for analysis arise from prevalent cohorts, where the date of infection is unknown for most or all individuals. As a result, standard curve fitting algorithms are not immediately applicable. Here we propose two methods to circumvent this difficulty. The first uses repeated measurement data to provide information not only on the level of the variable of interest, but also on its rate of change, while the second uses an estimate of the expected time since infection. Both methods are based on the principal curves algorithm of Hastie and Stuetzle, and are applied to data from a prevalent cohort of HIV-infected homosexual men, giving estimates of the average pattern of CD4+ lymphocyte decline. These methods are applicable to natural history studies using data from prevalent cohorts where the time of disease origin is uncertain, provided certain ancillary information is available from external sources.

Luminal substrate "brake" on mucosal maltase-glucoamylase activity regulates total rate of starch digestion to glucose

BACKGROUND: Starches are the major source of dietary glucose in weaned children and adults. However, small intestine alpha-glucogenesis by starch digestion is poorly understood due to substrate structural and chemical complexity, as well as the multiplicity of participating enzymes. Our objective was dissection of luminal and mucosal alpha-glucosidase activities participating in digestion of the soluble starch product maltodextrin (MDx). PATIENTS AND METHODS: Immunoprecipitated assays were performed on biopsy specimens and isolated enterocytes with MDx substrate. RESULTS: Mucosal sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM) contributed 85% of total in vitro alpha-glucogenesis. Recombinant human pancreatic alpha-amylase alone contributed <15% of in vitro alpha-glucogenesis; however, alpha-amylase strongly amplified the mucosal alpha-glucogenic activities by preprocessing of starch to short glucose oligomer substrates. At low glucose oligomer concentrations, MGAM was 10 times more active than SI, but at higher concentrations it experienced substrate inhibition whereas SI was not affected. The in vitro results indicated that MGAM activity is inhibited by alpha-amylase digested starch product "brake" and contributes only 20% of mucosal alpha-glucogenic activity. SI contributes most of the alpha-glucogenic activity at higher oligomer substrate concentrations. CONCLUSIONS: MGAM primes and SI activity sustains and constrains prandial alpha-glucogenesis from starch oligomers at approximately 5% of the uninhibited rate. This coupled mucosal mechanism may contribute to highly efficient glucogenesis from low-starch diets and play a role in meeting the high requirement for glucose during children's brain maturation. The brake could play a constraining role on rates of glucose production from higher-starch diets consumed by an older population at risk for degenerative metabolic disorders.

Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency

BACKGROUND: Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of urea metabolism that can lead to hyperammonemic crises and orotic aciduria. To date, a total of 341 causative mutations within the OTC gene have been described. However, in about 20% of the patients with enzymatically confirmed OTC deficiency no mutation can be detected when sequencing of genomic DNA analyzing exons and adjacent intronic segments of the OTC gene is performed. METHODS: Standard genomic DNA analysis of the OTC gene in five consecutive patients from five families revealed no mutation. Hence, liver tissue was obtained by needle sampling or open biopsy and RNA extracted from liver was analyzed. RESULTS: Complex rearrangements of the OTC transcript (three insertions and two deletions) were found in all five patients. CONCLUSION: In patients with a strong suspicion of OTC deficiency despite normal results of sequencing exonic regions of the OTC gene, characterization of liver OTC mRNA is highly effective in resolving the genotype. Liver tissue sampling by needle aspiration allows for both enzymatic analysis and RNA based diagnostics of OTC deficiency.

Isometric rate of force development, maximum voluntary contraction, and balance in women with and without joint hypermobility

OBJECTIVE: To determine differences between hypermobile subjects and controls in terms of maximum strength, rate of force development, and balance. METHODS: We recruited 13 subjects with hypermobility and 18 controls. Rate of force development and maximal voluntary contraction (MVC) during single leg knee extension of the right knee were measured isometrically for each subject. Balance was tested twice on a force plate with 15-second single-leg stands on the right leg. Rate of force development (N/second) and MVC (N) were extracted from the force-time curve as maximal rate of force development (= limit Deltaforce/Deltatime) and the absolute maximal value, respectively. RESULTS: The hypermobile subjects showed a significantly higher value for rate of force development (15.2% higher; P = 0.038, P = 0.453, epsilon = 0.693) and rate of force development related to body weight (16.4% higher; P = 0.018, P = 0.601, epsilon = 0.834) than the controls. The groups did not differ significantly in MVC (P = 0.767, P = 0.136, epsilon = 0.065), and MVC related to body weight varied randomly between the groups (P = 0.921, P = 0.050, epsilon = 0.000). In balance testing, the mediolateral sway of the hypermobile subjects showed significantly higher values (11.6% higher; P = 0.034, P = 0.050, epsilon = 0.000) than that of controls, but there was no significant difference (4.9% difference; P = 0.953, P = 0.050, epsilon = 0.000) in anteroposterior sway between the 2 groups. CONCLUSION: Hypermobile women without acute symptoms or limitations in activities of daily life have a higher rate of force development in the knee extensors and a higher mediolateral sway than controls with normal joint mobility.

Development of system separation strategy using synchrophasor data

In the current market system, power systems are operated at higher loads for economic reasons. Power system stability becomes a genuine concern in such operating conditions. In case of failure of any larger component, the system may become stressed. These events may start cascading failures, which may lead to blackouts. One of the main reasons of the major recorded blackout events has been the unavailability of system-wide information. Synchrophasor technology has the capability to provide system-wide real time information. Phasor Measurement Units (PMUs) are the basic building block of this technology, which provide the Global Positioning System (GPS) time-stamped voltage and current phasor values along with the frequency. It is being assumed that synchrophasor data of all the buses is available and thus the whole system is fully observable. This information can be used to initiate islanding or system separation to avoid blackouts. A system separation strategy using synchrophasor data has been developed to answer the three main aspects of system separation: (1) When to separate: One class support machines (OC-SVM) is primarily used for the anomaly detection. Here OC-SVM was used to detect wide area instability. OC-SVM has been tested on different stable and unstable cases and it is found that OC-SVM has the capability to detect the wide area instability and thus is capable to answer the question of “when the system should be separated”. (2) Where to separate: The agglomerative clustering technique was used to find the groups of coherent buses. The lines connecting different groups of coherent buses form the separation surface. The rate of change of the bus voltage phase angles has been used as the input to this technique. This technique has the potential to exactly identify the lines to be tripped for the system separation. (3) What to do after separation: Load shedding was performed approximately equal to the sum of power flows along the candidate system separation lines should be initiated before tripping these lines. Therefore it is recommended that load shedding should be initiated before tripping the lines for system separation.

The rate of outpatient cataract surgery in ten European countries: an analysis using data from the SHARE survey

BACKGROUND: The aim of this study was to determine the rates of outpatient cataract surgery (ROCS) in ten European countries and to find country-specific health indicators explaining the differences. METHODS: Using data from the Survey of Health, Ageing and Retirement in Europe (SHARE), 251 eligible respondents were identified for which cataract surgery was the last surgical procedure. The ROCS of ten countries were compared using logistic regression. The influence of the public expenditure on health as per cent of the total expenditure on health, of the number of acute care beds per 1,000 population, and of the number of practicing physicians per 1,000 population, was studied by multiple logistic regression. Additional information was obtained from country-specific opinion leaders in the field of cataract surgery. RESULTS: The ROCS differed significantly between the ten analysed European countries where Denmark had the highest (100%) and Austria the lowest (0%) rate of day care surgery. A decrease in the density of acute care beds (p < 0.0000001) and in the density of practicing physicians (p < 0.05) and an increase in the public expenditure on health as per cent of the total health expenditure (p < 0.01) lead to an increase in the ROCS. According to the opinion leaders, regulations and financial incentives also have a strong influence on the ROCS. CONCLUSIONS: The outpatient rate of cataract surgery in the ten European countries was mainly influenced by the acute-care beds density, but also by the density of practicing physicians, and by the public expenditure on health.

The Rate of Precipitation of Copper Aluminide in the Silver Rich Silver-Copper-Aluminum Alloys

In order to determine the best annealing temperature at which to age-harden the alloys, hardness tests on speci­men annealed for different lengths of time at different temperatures were made.

A Study of the Effect of Oxygen on the Rate of Dissolution of Gold in Cyanide Solutions.

The accepted chemical reactions in the dissolution of gold by cyanide solutions require the presence of gold, cyanide, water, and oxygen. The importance of dissolved oxygen in cyanide solutions as a factor is recognized by those familiar with cyanidation. Manufacturers of cyanidation equipment realize the necessity of oxygen, as shown by the appliances they have developed which are attached to the agitators in order to saturate the cyanide solutions with air.

The Effect of Temperature on the Rate of Dissolution of Gold in Cyanide Solutions which have a Constant Oxygen Content.

Since the development of cyanidation into a highly efficient process for treating gold ores, many papers have been written on its various aspects. Although, there has been much work done on it, the chemistry of the reaction is not yet completely understood.