A randomized controlled pilot study of VO2 max testing: a potential model for measuring relative in vivo efficacy of different red blood cell products.

BACKGROUND: Randomized trials, for example, RECESS, comparing "young" (median, 7-day) versus "middle-aged" (median, 28-day) red blood cells (RBCs), showed no difference in outcome. These data are important; however, they do not inform us about the safety and effectiveness of the oldest RBCs, which some patients receive. It may not be feasible to conduct a clinical trial randomizing patients to receive the oldest blood. Therefore, we propose strenuous exercise (VO2 max testing) as a model to study the relative efficacy to increase oxygen delivery to tissue of different RBC products, for example, extremes of storage duration. STUDY DESIGN AND METHODS: In this pilot study, eight healthy subjects had 2 units of leukoreduced RBCs collected by apheresis in AS-3 using standard methods. Subjects were randomized to receive both (2) units of their autologous RBCs at either 7 or 42 days after blood collection. VO2 max testing on a cycle ergometer was performed 2 days before (Monday) and 2 days after (Friday) the transfusion visit (Wednesday). This design avoids confounding effects on intravascular volume from the 2-unit blood transfusion. The primary outcome was the difference in VO2 max between Friday and Monday (delta VO2 max). RESULTS: VO2 max increased more in the 7-day RBC arm (8.7 ± 6.9% vs. 1.9 ± 6.5%, p = 0.202 for comparison between arms). Exercise duration (seconds) increased in the 7-day RBC arm (8.4 ± 1.7%) but actually decreased in the 42-day arm (-2.6 ± 3.6%, p = 0.002). CONCLUSIONS: This pilot study suggests that VO2 max testing has potential as a rigorous and quantitative in vivo functional assay of RBC function. Our preliminary results suggest that 42-day RBCs are inferior to 7-day RBCs at delivering oxygen to tissues.

The sequence and analysis of duplication-rich human chromosome 16.

Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.

Implementing Obstetric Early Warning Systems.

Severe maternal morbidity and mortality are often preventable and obstetric early warning systems that alert care providers of potential impending critical illness may improve maternal safety. While literature on outcomes and test characteristics of maternal early warning systems is evolving, there is limited guidance on implementation. Given current interest in early warning systems and their potential role in care, the 2017 Society for Maternal-Fetal Medicine (SMFM) Annual Meeting dedicated a session to exploring early warning implementation across a wide range of hospital settings. This manuscript reports on key points from this session. While implementation experiences varied based on factors specific to individual sites, common themes relevant to all hospitals presenting were identified. Successful implementation of early warnings systems requires administrative and leadership support, dedication of resources, improved coordination between nurses, providers, and ancillary staff, optimization of information technology, effective education, evaluation of and change in hospital culture and practices, and support in provider decision-making. Evolving data on outcomes on early warning systems suggest that maternal risk may be reduced. To effectively reduce maternal, risk early warning systems that capture deterioration from a broad range of conditions may be required in addition to bundles tailored to specific conditions such as hemorrhage, thromboembolism, and hypertension.

Sensory discrimination and intelligence: testing Spearman's other hypothesis.

At the centenary of Spearman's seminal 1904 article, his general intelligence hypothesis remains one of the most influential in psychology. Less well known is the article's other hypothesis that there is "a correspondence between what may provisionally be called 'General Discrimination' and 'General Intelligence' which works out with great approximation to one or absoluteness" (Spearman, 1904, p. 284). Studies that do not find high correlations between psychometric intelligence and single sensory discrimination tests do not falsify this hypothesis. This study is the first directly to address Spearman's general intelligence-general sensory discrimination hypothesis. It attempts to replicate his findings with a similar sample of schoolchildren. In a well-fitting structural equation model of the data, general intelligence and general discrimination correlated .92. In a reanalysis of data published byActon and Schroeder (2001), general intelligence and general sensory ability correlated .68 in men and women. One hundred years after its conception, Spearman's other hypothesis achieves some confirmation. The association between general intelligence and general sensory ability remains to be replicated and explained.

The complete genome sequence of Bacillus thuringiensis Al Hakam.

Bacillus thuringiensis is an insect pathogen that is widely used as a biopesticide (E. Schnepf, N. Crickmore, J. Van Rie, D. Lereclus, J. Baum, J. Feitelson, D. R. Zeigler, and D. H. Dean, Microbiol. Mol. Biol. Rev. 62:775-806, 1998). Here we report the finished, annotated genome sequence of B. thuringiensis Al Hakam, which was collected in Iraq by the United Nations Special Commission (L. Radnedge, P. Agron, K. Hill, P. Jackson, L. Ticknor, P. Keim, and G. Andersen, Appl. Environ. Microbiol. 69:2755-2764, 2003).

Pathogenomic sequence analysis of Bacillus cereus and Bacillus thuringiensis isolates closely related to Bacillus anthracis.

Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are closely related gram-positive, spore-forming bacteria of the B. cereus sensu lato group. While independently derived strains of B. anthracis reveal conspicuous sequence homogeneity, environmental isolates of B. cereus and B. thuringiensis exhibit extensive genetic diversity. Here we report the sequencing and comparative analysis of the genomes of two members of the B. cereus group, B. thuringiensis 97-27 subsp. konkukian serotype H34, isolated from a necrotic human wound, and B. cereus E33L, which was isolated from a swab of a zebra carcass in Namibia. These two strains, when analyzed by amplified fragment length polymorphism within a collection of over 300 of B. cereus, B. thuringiensis, and B. anthracis isolates, appear closely related to B. anthracis. The B. cereus E33L isolate appears to be the nearest relative to B. anthracis identified thus far. Whole-genome sequencing of B. thuringiensis 97-27and B. cereus E33L was undertaken to identify shared and unique genes among these isolates in comparison to the genomes of pathogenic strains B. anthracis Ames and B. cereus G9241 and nonpathogenic strains B. cereus ATCC 10987 and B. cereus ATCC 14579. Comparison of these genomes revealed differences in terms of virulence, metabolic competence, structural components, and regulatory mechanisms.

Carbon dioxide emulsion assisted loading of polymer microspheres toward sustained release materials.

An organic solvent-free method for encapsulating progesterone at high loadings within micron-sized inert latex polymer beads is reported. This approach makes use of a polymeric surfactant to emulsify carbon dioxide into an aqueous latex suspension. In this way, preformed approximately 4 microm polystyrene (PS) microparticles surface-grafted with poly(N-vinylpyrrolidone) (PVP) were plasticized and swollen followed by rapid partitioning of progesterone into the polymer matrix. The as-prepared polystyrene beads incorporated over 10% progesterone by weight while maintaining their initial size and morphological uniformity. Dissolution experiments were also carried out to obtain the release profile of progesterone entrapped within the PVP/PS particles.