Surface-modified and conventional nanocapsules as novel formulations for parenteral delivery of halofantrine

The aim of this work was to develop a stable injectable formulation of the antimalarial drug halofantrine (Hf) based on nanocapsules (NC) prepared from biodegradable polymers with Miglyol 810N as the oily core. Poly(D,L-lactide) PLA and its copolymers with poly(ethyleneglycol) (PLA-PEG) were used together with the surfactants poloxamer 188 and lecithin to yield NC with different surface properties. Highly efficient loading of the free base form of Hf was obtained; zeta potential measurements indicated that a part of the associated Hf was at the NC surface, interacting with the lecithin. NC were 150-250 nm in diameter and more stable on storage than nanoemulsions formed from oil and lecithin without polymer. The most stable NC, showing minimal size changes and flocculation, were those with a high density of 20-kDa PEG chains covalently grafted at the surface. Hf release from NC occurred mainly by partition with the external medium. In PBS, even when Tween 80 was added, release was limited to 20% of the total content, whatever the formulation. Addition of serum to the medium allowed complete and rapid release from PLA NC stabilized with adsorbed poloxamer 188, because of the high affinity of Hf for lipoproteins. However, the presence of covalently grafted PEG chains at the surface limited release by providing a hydrophilic steric barrier at the particle surface. A dense coverage with long PEG chains provided the best reduction of release. Such systems could constitute a long-circulating intravenous formulation of Hf for treating severe malaria.     

Dietary exposure estimates of 30 elements from the UK Total Diet Study

Dietary exposures of consumers to 30 elements (aluminium, antimony, arsenic, barium, bismuth, boron, cadmium, calcium, chromium, cobalt, copper, germanium, gold, iridium, iron, lead, lithium, manganese, mercury, molybdenum, nickel, palladium, platinum, rhodium, ruthenium, selenium, strontium, thallium, tin and zinc) estimated from the UK 1994 Total Diet Study are reported, and compared with those from previous UK Total Diet Studies and those from other countries. Dietary exposure estimates were generally low and, where comparisons are possible, similar to those from other countries and below the relevant Provisional Tolerable Weekly Intakes and Provisional Maximum Tolerable Daily Intakes. For most of those elements included in previous UK Total Diet Studies, dietary exposures have declined.     

Variation in bull beef quality due to ultimate muscle pH is correlated to endopeptidase and small heat shock protein levels

This study set out to determine if ultimate pH (pH_u) affected the performance of intracellular small heat shock protein and endopeptidase dynamics in muscle during beef ageing. Longissimus dorsi muscles from 39 Angus or Limousin × Angus bulls were examined to see if pH_u achieved at 22 h post mortem (rigor) affected tenderness and water holding capacity of beef. Samples were segregated into three pH_u groups termed high (pH > 6.3), intermediate (5.7 < pH < 6.3) and low (pH < 5.7) pH_u beef. More than 30% of bull beef did not achieve acceptable tenderness at 8 days post mortem with this ageing regime. No significant differences in calpain or cathepsin enzyme levels due to meat pH were observed until after 22 h post mortem, but low pH_u beef had elevated caspase 3/7 activity soon after slaughter. At 22 h post mortem, greater levels of μ-calpain enzyme were found in the high and intermediate pH_u beef and cathepsin B levels were superior in the low pH_u beef after 2 days post mortem. Different rates of desmin and troponin T protein degradation were also observed in aged bull beef. Both proteins were degraded within 6 h post mortem for high pH_u beef, but took >3 days post mortem for intermediate pH_u beef. High levels of alpha β-crystallin (aβC) at 22 h post mortem coincided with delayed muscle protein degradation for low pH_u beef. Our results support the hypothesis that aβC shields myofibrils and buffers against endopeptidase degradation of beef structure during ageing.     

Efficient processing of streaming updates with archived master data in near-real-time data warehousing

In order to make timely and effective decisions, businesses need the latest information from data warehouse repositories. To keep these repositories up-to-date with respect to end user updates, near-real-time data integration is required. An important phase in near-real-time data integration is data transformation where the stream of updates is joined with disk-based master data. The stream-based algorithm MESHJOIN (Mesh Join) has been proposed to amortize disk access over fast streams. MESHJOIN makes no assumptions about the data distribution. In real-world applications, however, skewed distributions can be found, such as a stream of products sold, where certain products are sold more frequently than the remainder of the products. The question arises is how much does MESHJOIN lose in terms of performance by not adapting to data skew. In this paper we perform a rigorous experimental study analyzing the possible performance improvements while considering typical data distributions. For this purpose we design an algorithm Extended Hybrid Join (X-HYBRIDJOIN) that is complementary to MESHJOIN in that it can adapt to data skew and stores parts of the master data in memory permanently, reducing the disk access overhead significantly. We compare the performance of X-HYBRIDJOIN against the performance of MESHJOIN. We take several precautions to make sure the comparison is adequate and focuses on the utilization of data skew. The experiments show that considering data skew offers substantial room for performance gains that cannot be found in non-adaptive approaches such as MESHJOIN. We also present a cost model for X-HYBRIDJOIN, and based on that cost model, the algorithm is tuned.     

On the declarative and procedural semantics of deductive object-oriented systems

We present declarative and procedural semantics for a deductive object-oriented language, Gulog. The declarative semantics is based on preferred minimal models. We describe both bottom-up and top-down query evaluation procedures and show that they are sound with respect to the declarative semantics. The results contribute to our understanding of the interaction of inheritance, overriding and deduction in the presence of both functional and set-valued methods, and multiple inheritance.     

Comprehensive process analysis of insight events in cognitive-behavioral and psychodynamic-interpersonal psychotherapies.

Comprehensive Process Analysis (CPA) is an interpretive, qualitative research method for analyzing significant therapy events. CPA was used to analyze 6 client-identified significant insight events in 2 treatments. Two events are presented in depth. The psychodynamic-interpersonal therapy event documented the existence of 2-part significant events and the value of key words. The cognitive-behavioral therapy event illustrated the role of context in transforming small therapy events into significant events. Events in both therapies involved therapist interpretations of recent difficult life events that were delivered in a firm but interactive style. Interpersonal therapy events were distinguished by links to themes from previous sessions and led to awareness of painful emotions. Cognitive therapy events were externalizing reattributions given to more clinically distressed clients. A revised 5-stage microprocess model of the insight is presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)