Validity of the Polar V800 heart rate monitor to measure RR intervals at rest

Purpose To assess the validity of RR intervals and short-term heart rate variability (HRV) data obtained from the Polar V800 heart rate monitor, in comparison to an electrocardiograph (ECG). Method Twenty participants completed an active orthostatic test using the V800 and ECG. An improved method for the identification and correction of RR intervals was employed prior to HRV analysis. Agreement of the data was assessed using intra-class correlation coefficients (ICC), Bland–Altman limits of agreement (LoA), and effect size (ES). Results A small number of errors were detected between ECG and Polar RR signal, with a combined error rate of 0.086 %. The RR intervals from ECG to V800 were significantly different, but with small ES for both supine corrected and standing corrected data (ES 0.999 for both supine and standing corrected intervals. When analysed with the same HRV software no significant differences were observed in any HRV parameters, for either supine or standing; the data displayed small bias and tight LoA, strong ICC (>0.99) and small ES (≤0.029). Conclusions The V800 improves over previous Polar models, with narrower LoA, stronger ICC and smaller ES for both the RR intervals and HRV parameters. The findings support the validity of the Polar V800 and its ability to produce RR interval recordings consistent with an ECG. In addition, HRV parameters derived from these recordings are also highly comparable

Enumeration of islets by nuclei counting and light microscopic analysis

Author Manuscript 2011 May 1.Islet enumeration in impure preparations by conventional dithizone staining and visual counting is inaccurate and operator dependent. We examined nuclei counting for measuring the total number of cells in islet preparations, and we combined it with morphological analysis by light microscopy (LM) for estimating the volume fraction of islets in impure preparations. Cells and islets were disrupted with lysis solution and shear, and accuracy of counting successively diluted nuclei suspensions was verified with (1) visual counting in a hemocytometer after staining with crystal violet, and automatic counting by (2) aperture electrical resistance measurement and (3) flow cytometer measurement after staining with 7-aminoactinomycin-D. DNA content averaged 6.5 and 6.9 pg of DNA per cell for rat and human islets, respectively, in agreement with literature estimates. With pure rat islet preparations, precision improved with increasing counts, and samples with about greater than or equal to 160 islets provided a coefficient of variation of about 6%. Aliquots of human islet preparations were processed for LM analysis by stereological point counting. Total nuclei counts and islet volume fraction from LM analysis were combined to obtain the number of islet equivalents (IEs). Total number of IE by the standard method of dithizone staining/manual counting was overestimated by about 90% compared with LM/nuclei counting for 12 freshly isolated human islet research preparations. Nuclei counting combined with islet volume fraction measurements from LM is a novel method for achieving accurate islet enumeration.National Institutes of Health (U.S.) (Grant NCRR ICR U4Z 16606)National Institutes of Health (U.S.) (Grant R01-DK063108-01A1)National Institutes of Health (U.S.) (Grant NCRR ICR U42 RR0023244-01)Joslin Diabetes and Endocrinology Research Center (Grant DK36836)Diabetes Research & Wellness FoundationJuvenile Diabetes Research Foundation International (Islet Transplantation, Harvard Medical School

High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo

Economic and other barriers to adopting recommendations to prevent childhood obesity: results of a focus group study with parents

Abstract Background Parents are integral to the implementation of obesity prevention and management recommendations for children. Exploration of barriers to and facilitators of parental decisions to adopt obesity prevention recommendations will inform future efforts to reduce childhood obesity. Methods We conducted 4 focus groups (2 English, 2 Spanish) among a total of 19 parents of overweight (BMI ≥ 85th percentile) children aged 5-17 years. The main discussion focused on 7 common obesity prevention recommendations: reducing television (TV) watching, removing TV from child's bedroom, increasing physically active games, participating in community or school-based athletics, walking to school, walking more in general, and eating less fast food. Parents were asked to discuss what factors would make each recommendation more difficult (barriers) or easier (facilitators) to follow. Participants were also asked about the relative importance of economic (time and dollar costs/savings) barriers and facilitators if these were not brought into the discussion unprompted. Results Parents identified many barriers but few facilitators to adopting obesity prevention recommendations for their children. Members of all groups identified economic barriers (time and dollar costs) among a variety of pertinent barriers, although the discussion of dollar costs often required prompting. Parents cited other barriers including child preference, difficulty with changing habits, lack of information, lack of transportation, difficulty with monitoring child behavior, need for assistance from family members, parity with other family members, and neighborhood walking safety. Facilitators identified included access to physical activity programs, availability of alternatives to fast food and TV which are acceptable to the child, enlisting outside support, dietary information, involving the child, setting limits, making behavior changes gradually, and parental change in shopping behaviors and own eating behaviors. Conclusions Parents identify numerous barriers to adopting obesity prevention recommendations, most notably child and family preferences and resistance to change, but also economic barriers. Intervention programs should consider the context of family priorities and how to overcome barriers and make use of relevant facilitators during program development.http://deepblue.lib.umich.edu/bitstream/2027.42/78270/1/1471-2431-9-81.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78270/2/1471-2431-9-81.pdfPeer Reviewe

Community first responders and responder schemes in the United Kingdom: systematic scoping review

Background: Community First Responder (CFR) schemes support lay people to respond to medical emergencies, working closely with ambulance services. They operate widely in the UK. There has been no previous review of UK literature on these schemes. This is the first systematic scoping review of UK literature on CFR schemes, which identifies the reasons for becoming a CFR, requirements for training and feedback and confusion between the CFR role and that of ambulance service staff. This study also reveals gaps in the evidence base for CFR schemes. Methods: We conducted a systematic scoping review of the published literature, in the English language from 2000 onwards using specific search terms in six databases. Narrative synthesis was used to analyse article content. Results: Nine articles remained from the initial search of 15,969 articles after removing duplicates, title and abstract and then full text review. People were motivated to become CFRs through an altruistic desire to help others. They generally felt rewarded by their work but recognised that the help they provided was limited by their training compared with ambulance staff. There were concerns about the possible emotional impact on CFRs responding to incidents. CFRs felt that better feedback would enhance their learning. Ongoing training and support were viewed as essential to enable CFRs to progress. They perceived that public recognition of the CFR role was low, patients sometimes confusing them with ambulance staff. Relationships with the ambulance service were sometimes ambivalent due to confusion over roles. There was support for local autonomy of CFR schemes but with greater sharing of best practice. Discussion: Most studies dated from 2005 and were descriptive rather than analytical. In the UK and Australia CFRs are usually lay volunteers equipped with basic skills for responding to medical emergencies, whereas in the US they include other emergency staff as well as lay people. Conclusion: Opportunities for future research include exploring experiences and perceptions of patients who have been treated by CFRs and other stakeholders, while also evaluating the effectiveness and costs of CFR schemes

Cirsium species show disparity in patterns of genetic variation at their range-edge, despite similar patterns of reproduction and isolation

Genetic variation was assessed across the UK geographical range of Cirsium acaule and Cirsium heterophyllum. A decline in genetic diversity and increase in population divergence approaching the range edge of these species was predicted based on parallel declines in population density and seed production reported seperately. Patterns were compared with UK populations of the widespread Cirsium arvense.Populations were sampled along a latitudinal transect in the UK and genetic variation assessed using microsatellite markers. Cirsium acaule shows strong isolation by distance, a significant decline in diversity and an increase in divergence among range-edge populations. Geographical structure is also evident in C. arvense, whereas no such patterns are seen in C.heterophyllum. There is a major disparity between patterns of genetic variation in C. acaule and C. heterophyllum despite very similar patterns in seed production and population isolation in these species. This suggests it may be misleading to make assumptions about the geographical structure of genetic variation within species based solely on the present-day reproduction and distribution of populations

Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner