Efficacy, tolerability and risk factors for virological failure of darunavir-based therapy for treatment-experienced HIV-infected patients: the Swiss HIV Cohort Study.

OBJECTIVES: Darunavir was designed for activity against HIV resistant to other protease inhibitors (PIs). We assessed the efficacy, tolerability and risk factors for virological failure of darunavir for treatment-experienced patients seen in clinical practice. METHODS: We included all patients in the Swiss HIV Cohort Study starting darunavir after recording a viral load above 1000 HIV-1 RNA copies/mL given prior exposure to both PIs and nonnucleoside reverse transcriptase inhibitors. We followed these patients for up to 72 weeks, assessed virological failure using different loss of virological response algorithms and evaluated risk factors for virological failure using a Bayesian method to fit discrete Cox proportional hazard models. RESULTS: Among 130 treatment-experienced patients starting darunavir, the median age was 47 years, the median duration of HIV infection was 16 years, and 82% received mono or dual antiretroviral therapy before starting highly active antiretroviral therapy. During a median patient follow-up period of 45 weeks, 17% of patients stopped taking darunavir after a median exposure of 20 weeks. In patients followed beyond 48 weeks, the rate of virological failure at 48 weeks was at most 20%. Virological failure was more likely where patients had previously failed on both amprenavir and saquinavir and as the number of previously failed PI regimens increased. CONCLUSIONS: As a component of therapy for treatment-experienced patients, darunavir can achieve a similar efficacy and tolerability in clinical practice to that seen in clinical trials. Clinicians should consider whether a patient has failed on both amprenavir and saquinavir and the number of failed PI regimens before prescribing darunavir.

Postharvest mechanical damage affects fruit quality of 'Montenegrina' and 'Rainha' tangerines

The objective of this work was to evaluate the visual and chemical quality of tangerines after mechanical damage by impacts. The tangerine cultivars Montenegrina and Rainha were submitted to different degrees of impact and evaluated for decay and oleocellosis, loss of fresh weight, total soluble solids, total titratable acidity and ascorbic acid degradation, as well as for epicarp color changes. Experiments with three replicates and experimental units of six fruit for each cultivar were done in a completely randomized design. Impact produced qualitative internal and minor external changes on tangerines. The main modifications produced by impact on the fruit were losses of citric acid and soluble solids, which increased the solid:acid ratio, and losses of ascorbic acid. 'Montenegrina' tangerines are more susceptible to internal quality damage than 'Rainha'.

Forage potential and silage quality of four varieties of saccharine sorghum

Abstract: The objective of this work was to evaluate four cultivars of saccharine sorghum (Sorghum bicolor) regarding productivity, chemical composition of plant parts, and quality of the ensiling process. The tested varieties of saccharine sorghum were BRS 506, BRS 508, BRS 509, and BRS 511. The experiment was divided into two trials, which assessed: production, morphological composition, and nutritional quality of the saccharine varieties; and fermentation quality and nutritional value of the silage produced from the saccharine varieties. Of the tested varieties, BRS 509 and BRS 511 showed the highest total dry matter (DM) production. The BRS 508 variety presented the highest in vitro digestibility of the whole plant (70.65% DM). During ensiling, the BRS 509 variety showed the lowest DM loss (8.87%). The highest effluent production was observed for BRS 506 and BRS 508, with yields of 521.87 and 393.16 kg Mg-1 ensiled DM, respectively. The BRS 511 variety is the most recommended because of the best results for plant production and nutritional quality. Regarding the ensiling process, BRS 509 presents the lowest fermentation losses and the highest nutritional value of silage.

Current and future trens in the quality control of pharmaceuticals and biopharmaticals : impacts on Cost of Goods Sold (COGS)

[Summary] 2. Roles of quality control in the pharmaceutical and biopharmaceutical industries. - 2.1. Pharmaceutical industry. - 2.2. Biopharmaceutical industry. - 2.3. Policy and regulatory. - 2.3.1. The US Food and Drug Administration (FDA). - 2.3.2. The European Medicine Agency (EMEA). - 2.3.3. The Japanese Ministry of Work, Labor and Welfare (MHLW). - 2.3.4. The Swiss Agency for Therapeutic Products (Swissmedic). - 2.3.5. The International Conference on Harmonization (ICH). - - 3. Types of testing. - 3.1. Microbiological purity tests. - 3.2. Physiochemical tests. - 3.3. Critical to quality steps. - 3.3.1. API starting materials and excipients. - 3.3.2. Intermediates. - 3.3.3. APIs (drug substances) and final drug product. - 3.3.4. Primary and secondary packaging materials fro drug products. - - 4. Manufacturing cost and quality control. - 4.1.1. Pharmaceutical manufacturing cost breakdown. - 4.1.2. Biopharmaceutical manufacturing cost breakdown. - 4.2. Batch failure / rejection / rework / recalls. - - 5. Future trends in the quality control of pharmaceuticals and biopharmaceuticals. - 5.1. Rapid and real time testing. - 5.1.1. Physio-chemicals testing. - 5.1.2. Rapid microbiology methods

The Effect of Operational Disturbances on Reliability and Operation Time Distribution of NCmachine Tools in FMS

This thesis concentrates on studying the operational disturbance behavior of machine tools integrated into FMS. Operational disturbances are short term failures of machine tools which are especially disruptive to unattended or unmanned operation of FMS. The main objective was to examine the effect of operational disturbances on reliability and operation time distribution for machine tools. The theoretical part of the thesis covers the fimdamentals of FMS relating to the subject of this study. The concept of FMS, its benefits and operator's role in FMS operation are reviewed. The importance of reliability is presented. The terms describing the operation time of machine tools are formed by adopting standards and references. The concept of failure and indicators describing reliability and operational performance for machine tools in FMSs are presented. The empirical part of the thesis describes the research methodology which is a combination of automated (ADC) and manual data collection. By using this methodology it is possible to have a complete view of the operation time distribution for studied machine tools. Data collection was carried out in four FMSs consisting of a total of 17 machine tools. Each FMS's basic features and the signals of ADC are described. The indicators describing the reliability and operation time distribution of machine tools were calculated according to collected data. The results showed that operational disturbances have a significant influence on machine tool reliability and operational performance. On average, an operational disturbance occurs every 8,6 hours of operation time and has a down time of 0,53 hours. Operational disturbances cause a 9,4% loss in operation time which is twice the amount of losses caused by technical failures (4,3%). Operational disturbances have a decreasing influence on the utilization rate. A poor operational disturbance behavior decreases the utilization rate. It was found that the features of a part family to be machined and the method technology related to it are defining the operational disturbance behavior of the machine tool. Main causes for operational disturbances were related to material quality variations, tool maintenance, NC program errors, ATC and machine tool control. Operator's role was emphasized. It was found that failure recording activity of the operators correlates with the utilization rate. The more precisely the operators record the failure, the higher is the utilization rate. Also the FMS organizations which record failures more precisely have fewer operational disturbances.

Supply chain costs of a small board lot: sheet cutting and logistics

Succeeding in small board lot (0-20 tons) deliveries, is not always prosperous and failures as well as extra costs compared to standard costs arise. Failure deliveries from converting plants to customer locations tie a lot of unwanted and unexpected costs. Extra costs are handled as quality costs and more precise, internal failure costs. These costs revolve from unsuccessful truck payloads, redundant warehousing or unfavorable routing as examples. Quality costs are becoming more and more important factor in company’s financial decision making. Actual, realized truck payload correlates with the extra costs occurring, so filling the truck payload all get-out well is a key to lower the extra costs. Case company in this study is Corporation A, business segment Boards. Boards have outsourced half of their converting in order to gain better customer service via flexibility, lead time reductions and logistics efficiency improvements. Examination period of the study is first two quarters of year 2008 and deliveries examined are from converters to the customer locations. In Corporation A’s case, the total loss in failure deliveries is hundreds of thousands of Euros during the examination period. So, the logistics goal of getting the right product to the right place and right time for the least cost, does not completely realize.

Identifying reasons for failure in biomedical research and publishing

The regular assessment of Brazilian scientific output means that individual university departments need to constantly improve the quantity and quality of their scientific output. A significant proportion of this output involves the work of Master’s and Doctoral students, but getting this work published in a suitable journal can often prove to be a challenge. Although students’ lack of fluency in English is a contributing factor, many of the problems observed have an early origin in the formulation of the research problem and its relevance to current research trends in the international literature. In short, more time needs to be spent in the library and less in the laboratory, and more effort needs to be made in teaching students basic research skills such as the effective use of bibliographic databases like PubMed, Web of Science and Scopus.

Quality of yellow passion fruit stored under refrigeration and controlled atmosphere

In this study, it was evaluated the quality of yellow passion fruits stored under refrigeration and controlled atmospheres of different composition aiming to extend the postharvest life of the fruits. The characteristics of skin color, appearance, mass loss, as well as the chemical quality of the juice of yellow passion fruits stored at: 21% O2 plus 0.03% CO2; 1% O2 plus 0.03% CO2; 5% O2 plus 0.03% CO2; 12% O2 plus 5% CO2; and 5% O2 plus 15% CO2, with 1 control treatment (refrigeration at 13 ºC and 90% UR) were determined. The analyses were performed before and after 30 days of storage and after removing the controlled atmospheres and storage for 9 days under refrigeration at ambient atmosphere. The data were interpreted by simple statistical analysis using the test by confidence intervals with 95% of probability. It was concluded that the application of atmospheres with low oxygen concentration and high carbon dioxide level minimized quality losses. At atmosphere with 5% O2 and 15% CO2, it was observed the lowest color change indexes and mass loss, and also the smallest decrease in acidity, soluble solids content, vitamin C, reducing sugars, and total soluble sugars.

Failure Mode and Effect Analysis (FMEA) for confectionery manufacturing in developing countries: Turkish delight production as a case study

The Failure Mode and Effect Analysis (FMEA) was applied for risk assessment of confectionary manufacturing, in whichthe traditional methods and equipment were intensively used in the production. Potential failure modes and effects as well as their possible causes were identified in the process flow. Processing stages that involve intensive handling of food by workers had the highest risk priority numbers (RPN = 216 and 189), followed by chemical contamination risks in different stages of the process. The application of corrective actions substantially reduced the RPN (risk priority number) values. Therefore, the implementation of FMEA (The Failure Mode and Effect Analysis) model in confectionary manufacturing improved the safety and quality of the final products.

Forced-air, vacuum, and hydro precooling of cauliflower (Brassica oleracea L. var. botrytis cv. Freemont): Part II. Determination of quality parameters during storage

Cauliflower heads, which were precooled using four different methods including vacuum, forced-air, and high and low flow hydro precooling, were stored under controlled atmosphere and room conditions. Controlled atmosphere conditions (CA) were as follows: 1°C temperature, 90 ± 5% relative humidity, and 0:21 [(%CO2:%O2) – (0:21) control] atmosphere composition. Room conditions (RC) were: 22±1°C temperature and 55-60% humidity. Various quality parameters of the cauliflower heads were assessed during storage (days 0, 7, 14, 21, 28, and 35) under controlled atmosphere and room conditions (days 0, 5, and 10). During storage, weight loss, deterioration rate, overall sensory quality score, hardness, and colour (L, a, b, C and α) were evaluated. In the present study, the strength and quality parameters of cauliflower under CA and RC conditions were obtained. Vacuum precooling was found to be most suitable method before cauliflower was submitted to cold storage and sent to market. Furthermore, the storage of cauliflower without precooling resulted in a significant decrease in quality parameters.

Influence of compounding and process variables on quality of condams made from natural rubber latex

Condoms are widely accepted as a contraceptive for family planning and population control. It is also accepted as the most effective barrier against sexually transmitted diseases, especially AIDS, the incurable disease. But presence of pinholes and low film strength of condoms make it unsuitable for the purpose. Quality improvement of condoms by reducing the pinhole formation and increasing the film strength is thus an essential requirement for population control as well as for preventing the spread of sexually transmitted diseases. Strict implementation of WHO specification of condoms further increases the rejection percentage. This causes higher rejection loss to condom manufacturers because the defects could be identified only at the final stage of processing. If the influence of various factors which cause these defects is known, manufacturers can take remedial measures to reduce the defectives so that rejection loss can be decreased and quality of condoms increased. In the present study, it was proposed to conduct experiments to improve the quality of condoms by reducing the pinhole rejection percentage and increasing the tensile properties, burst volume, and burst pressure. Ageing property improvement also was an important target among other parameters. Until a cure for AIDS is found, a high quality latex condom is the only effective device in the prevention of the spread of HIV, AIDS and STD's. Hence it is all the more necessary to have high quality condoms.

Nuclear accumulation of myocyte muscle LIM protein is regulated by heme oxygenase 1 and correlates with cardiac function in the transition to failure

Impaired mechanosensing leads to heart failure and we have previously shown that a decreased ratio of cytoplasmic to nuclear CSRP3/Muscle LIM protein (MLP ratio) is associated with a loss of mechanosensitivity. Here we tested whether passive or active stress/strain was important in modulating the MLP ratio and determined whether this correlated with heart function during the transition to failure. We exposed cultured neonatal rat myocytes to 10% cyclic mechanical stretch at 1 Hz, or electrically paced myocytes at 6.8 V (1 Hz) for 48 h. The MLP ratio decreased 50% (P < 0.05, n = 4) only in response to electrical pacing, suggesting impaired mechanosensitivity. Inhibition of contractility with 10 μM blebbistatin resulted in a ∼3 fold increase in the MLP ratio (n = 8, P < 0.05), indicating that myocyte contractility regulates nuclear MLP. Inhibition of histone deacetylase (HDAC) signaling with trichostatin A increased nuclear MLP following passive stretch, suggesting that HDACs block MLP nuclear accumulation. Inhibition of heme-oxygenase1 (HO-1) activity with PPZII blocked MLP nuclear accumulation. To examine how mechanosensitivity changes during the transition to heart failure, we studied a guinea pig model of angiotensin II infusion (400 ng/kg/min) over 12 weeks. Using subcellular fractionation we showed that the MLP ratio increased 88% (n = 4, P < 0.01) during compensated hypertrophy, but decreased significantly during heart failure (P < 0.001, n = 4). The MLP ratio correlated significantly with the E/A ratio (r = 0.71, P < 0.01 n = 12), a clinical measure of diastolic function. These data indicate for the first time that myocyte mechanosensitivity as indicated by the MLP ratio is regulated primarily by myocyte contractility via HO-1 and HDAC signaling.

Egg quality during storage and deposition of minerals in eggs from quails fed diets supplemented with organic selenium, zinc and manganese

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chicken meat quality as a function of fasting period and water spray

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genetic association study between Interleukin 10 gene and dental implant loss

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)