Comprehensive Peroxidase-Based Hematologic Profiling for The Prediction of 1-Year Myocardial Infarction and Death

Background— Recognition of biological patterns holds promise for improved identification of patients at risk for myocardial infarction (MI) and death. We hypothesized that identifying high- and low-risk patterns from a broad spectrum of hematologic phenotypic data related to leukocyte peroxidase-, erythrocyte- and platelet-related parameters may better predict future cardiovascular risk in stable cardiac patients than traditional risk factors alone. Methods and Results— Stable patients (n=7369) undergoing elective cardiac evaluation at a tertiary care center were enrolled. A model (PEROX) that predicts incident 1-year death and MI was derived from standard clinical data combined with information captured by a high-throughput peroxidase-based hematology analyzer during performance of a complete blood count with differential. The PEROX model was developed using a random sampling of subjects in a derivation cohort (n=5895) and then independently validated in a nonoverlapping validation cohort (n=1474). Twenty-three high-risk (observed in ≥10% of subjects with events) and 24 low-risk (observed in ≥10% of subjects without events) patterns were identified in the derivation cohort. Erythrocyte- and leukocyte (peroxidase)-derived parameters dominated the variables predicting risk of death, whereas variables in MI risk patterns included traditional cardiac risk factors and elements from all blood cell lineages. Within the validation cohort, the PEROX model demonstrated superior prognostic accuracy (78%) for 1-year risk of death or MI compared with traditional risk factors alone (67%). Furthermore, the PEROX model reclassified 23.5% (P\u3c0.001) of patients to different risk categories for death/MI when added to traditional risk factors. Conclusion— Comprehensive pattern recognition of high- and low-risk clusters of clinical, biochemical, and hematologic parameters provided incremental prognostic value in stable patients having elective diagnostic cardiac catheterization for 1-year risks of death and MI

Comprehensive Peroxidase-Based Hematologic Profiling for The Prediction of 1-Year Myocardial Infarction and Death

Background— Recognition of biological patterns holds promise for improved identification of patients at risk for myocardial infarction (MI) and death. We hypothesized that identifying high- and low-risk patterns from a broad spectrum of hematologic phenotypic data related to leukocyte peroxidase-, erythrocyte- and platelet-related parameters may better predict future cardiovascular risk in stable cardiac patients than traditional risk factors alone. Methods and Results— Stable patients (n=7369) undergoing elective cardiac evaluation at a tertiary care center were enrolled. A model (PEROX) that predicts incident 1-year death and MI was derived from standard clinical data combined with information captured by a high-throughput peroxidase-based hematology analyzer during performance of a complete blood count with differential. The PEROX model was developed using a random sampling of subjects in a derivation cohort (n=5895) and then independently validated in a nonoverlapping validation cohort (n=1474). Twenty-three high-risk (observed in ≥10% of subjects with events) and 24 low-risk (observed in ≥10% of subjects without events) patterns were identified in the derivation cohort. Erythrocyte- and leukocyte (peroxidase)-derived parameters dominated the variables predicting risk of death, whereas variables in MI risk patterns included traditional cardiac risk factors and elements from all blood cell lineages. Within the validation cohort, the PEROX model demonstrated superior prognostic accuracy (78%) for 1-year risk of death or MI compared with traditional risk factors alone (67%). Furthermore, the PEROX model reclassified 23.5% (P\u3c0.001) of patients to different risk categories for death/MI when added to traditional risk factors. Conclusion— Comprehensive pattern recognition of high- and low-risk clusters of clinical, biochemical, and hematologic parameters provided incremental prognostic value in stable patients having elective diagnostic cardiac catheterization for 1-year risks of death and MI

Public health professionals' perceptions toward provision of health protection in England: a survey of expectations of Primary Care Trusts and Health Protection Units in the delivery of health protection

BACKGROUND: Effective health protection requires systematised responses with clear accountabilities. In England, Primary Care Trusts and the Health Protection Agency both have statutory responsibilities for health protection. A Memorandum of Understanding identifies responsibilities of both parties, but there is a potential lack of clarity about responsibility for specific health protection functions. We aimed to investigate professionals' perceptions of responsibility for different health protection functions, to inform future guidance for, and organisation of, health protection in England. METHODS: We sent a postal questionnaire to all health protection professionals in England from the following groups: (a) Directors of Public Health in Primary Care Trusts; (b) Directors of Health Protection Units within the Health Protection Agency; (c) Directors of Public Health in Strategic Health Authorities and; (d) Regional Directors of the Health Protection Agency RESULTS: The response rate exceeded 70%. Variations in perceptions of who should be, and who is, delivering health protection functions were observed within, and between, the professional groups (a)-(d). Concordance in views of which organisation should, and which does deliver was high (≥90%) for 6 of 18 health protection functions, but much lower (≤80%) for 6 other functions, including managing the implications of a case of meningitis out of hours, of landfill environmental contamination, vaccination in response to mumps outbreaks, nursing home infection control, monitoring sexually transmitted infections and immunisation training for primary care staff. The proportion of respondents reporting that they felt confident most or all of the time in the safe delivery of a health protection function was strongly correlated with the concordance (r = 0.65, P = 0.0038). CONCLUSION: Whilst we studied professionals' perceptions, rather than actual responses to incidents, our study suggests that there are important areas of health protection where consistent understanding of responsibility for delivery is lacking. There are opportunities to clarify the responsibility for health protection in England, perhaps learning from the approaches used for those health protection functions where we found consistent perceptions of accountability

Diverse protostellar evolutionary states in the young cluster AFGL961

We present arcsecond resolution mid-infrared and millimeter observations of the center of the young stellar cluster AFGL961 in the Rosette molecular cloud. Within 0.2 pc of each other, we find an early B star embedded in a dense core, a neighboring star of similar luminosity with no millimeter counterpart, a protostar that has cleared out a cavity in the circumcluster envelope, and two massive, dense cores with no infrared counterparts. An outflow emanates from one of these cores, indicating a deeply embedded protostar, but the other is starless, bound, and appears to be collapsing. The diversity of states implies either that protostellar evolution is faster in clusters than in isolation or that clusters form via quasi-static rather than dynamic collapse. The existence of a pre-stellar core at the cluster center shows that that some star formation continues after and in close proximity to massive, ionizing stars.Comment: 22 pages, 7 figures, accepted for publication in Ap

High on-off conductance switching ratio in optically-driven self-assembled conjugated molecular systems

A new azobenzene-thiophene molecular switch is designed, synthesized and used to form self-assembled monolayers (SAM) on gold. An "on/off" conductance ratio up to 7x1E3 (with an average value of 1.5x1E3) is reported. The "on" conductance state is clearly identified to the cis isomer of the azobenzene moiety. The high "on/off" ratio is explained in terms of photo-induced, configuration-related, changes in the electrode-molecule interface energetics (changes in the energy position of the molecular orbitals with respect to the Fermi energy of electrodes) in addition to changes in the tunnel barrier length (length of the molecules). First principles DFT calculations demonstrate a better delocalization of the frontier orbitals, as well as a stronger electronic coupling between the azobenzene moiety and the electrode for the cis configuration over the trans one. Measured photoionization cross-sections for the molecules in the SAM are close to the known values for azobenzene derivatives in solution.Comment: 1 file with main text, figure and suppementary informatio

Liposomal Packaging Generates Wnt Protein with In Vivo Biological Activity

Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context

DRD4 Polymorphism Moderates the Effect of Alcohol Consumption on Social Bonding

Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition) ×2 (genotype) design (N = 422) to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR) polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse