Real time spatial cluster detection using interpoint distances among precise patient locations

BACKGROUND: Public health departments in the United States are beginning to gain timely access to health data, often as soon as one day after a visit to a health care facility. Consequently, new approaches to outbreak surveillance are being developed. When cases cluster geographically, an analysis of their spatial distribution can facilitate outbreak detection. Our method focuses on detecting perturbations in the distribution of pair-wise distances among all patients in a geographical region. Barring outbreaks, this distribution can be quite stable over time. We sought to exemplify the method by measuring its cluster detection performance, and to determine factors affecting sensitivity to spatial clustering among patients presenting to hospital emergency departments with respiratory syndromes. METHODS: The approach was to (1) define a baseline spatial distribution of home addresses for a population of patients visiting an emergency department with respiratory syndromes using historical data; (2) develop a controlled feature set simulation by inserting simulated outbreak data with varied parameters into authentic background noise, thereby creating semisynthetic data; (3) compare the observed with the expected spatial distribution; (4) establish the relative value of different alarm strategies so as to maximize sensitivity for the detection of clustering; and (5) measure factors which have an impact on sensitivity. RESULTS: Overall sensitivity to detect spatial clustering was 62%. This contrasts with an overall alarm rate of less than 5% for the same number of extra visits when the extra visits were not characterized by geographic clustering. Clusters that produced the least number of alarms were those that were small in size (10 extra visits in a week, where visits per week ranged from 120 to 472), diffusely distributed over an area with a 3 km radius, and located close to the hospital (5 km) in a region most densely populated with patients to this hospital. Near perfect alarm rates were found for clusters that varied on the opposite extremes of these parameters (40 extra visits, within a 250 meter radius, 50 km from the hospital). CONCLUSION: Measuring perturbations in the interpoint distance distribution is a sensitive method for detecting spatial clustering. When cases are clustered geographically, there is clearly power to detect clustering when the spatial distribution is represented by the M statistic, even when clusters are small in size. By varying independent parameters of simulated outbreaks, we have demonstrated empirically the limits of detection of different types of outbreaks

Concurrent and longitudinal correlates of preschool peer sociometrics: Comparing rating scale and nomination measures

Nomination and rating scale measures of preschool sociometric status were compared with respect to their patterns of concurrent and longitudinal developmental correlates. The study was undertaken to help fill a void in the empirical literature on young children's peer adjustment. Subjects were 79 4-5 year-old children, currently enrolled in preschool classes. In addition to the sociometric interviews, diverse measures of children's social and cognitive competence were administered concurrently, and longitudinally one year later. These measures included teacher ratings of peer acceptance and behavior problems, and performance measures of social problem-solving ability, impulse control, and vocabulary competence. As expected, the reliability of the rating scale technique was superior to that of the nomination measures. Furthermore, all three sociometric measures had modest but meaningful patterns of concurrent and longitudinal correlates. However, the negative nomination measure was distinguished from the others by its consistent association with measures of impulsivity, and its predictive link with aggressive social problem solving. Therefore, negative peer nomination measures supply unique information about children's social functioning that should be represented in studies of children at risk for social maladjustment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27123/1/0000115.pd

Quantitative PCR assays for detection of five Alaskan fish species: Lota lota, Salvelinus alpinus, Salvelinus malma, Thymallus arcticus, and Cottus cognatus from environmental DNA

The North Slope of Alaska contains arctic fish populations that are important for subsistence of local human populations, and under threat from natural resource extraction and climate change. We designed and evaluated four quantitative PCR assays for detection of environmental DNA from five Alaskan fish species present on the North Slope of Alaska: burbot (Lota lota), arctic char (Salvelinus alpinus), Dolly Varden (Salvelinus malma), arctic grayling (Thymallus arcticus), and slimy sculpin (Cottus cognatus). All assays were designed and tested for species specificity and sensitivity, and all assays detected target species from filtered water samples collected from the field. These assays will enable efficient and economical detection of the above species from lakes and rivers. This in turn will provide managers with improved knowledge of current distributions and future range shifts associated with climate and development threats, enabling more timely management

Quantitative PCR Assays for Detection of Five Arctic Fish Species: \u3ci\u3eLota lota\u3c/i\u3e, \u3ci\u3eCottus cognatus\u3c/i\u3e, \u3ci\u3eSalvelinus alpinus\u3c/i\u3e, \u3ci\u3eSalvelinus malma\u3c/i\u3e, and \u3ci\u3eThymallus arcticus\u3c/i\u3e from Environmental DNA

The North Slope of Alaska contains arctic fish populations that are important for subsistence of local human populations, and are under threat from natural resource extraction and climate change. We designed and evaluated four quantitative PCR assays for the detection of environmental DNA from five Alaskan fish species present on the North Slope of Alaska: burbot (Lota lota), arctic char (Salvelinus alpinus), Dolly Varden (Salvelinus malma), arctic grayling (Thymallus arcticus), and slimy sculpin (Cottus cognatus). All assays were designed and tested for species specificity and sensitivity, and all assays detected target species from filtered water samples collected from the field. These assays will enable efficient and economical detection and monitoring of these species in lakes and rivers. This in turn will provide managers with improved knowledge of current distributions and future range shifts associated with climate and development threats, enabling more timely management

Corporate Security Responsibility: Towards a Conceptual Framework for a Comparative Research Agenda

The political debate about the role of business in armed conflicts has increasingly raised expectations as to governance contributions by private corporations in the fields of conflict prevention, peace-keeping and postconflict peace-building. This political agenda seems far ahead of the research agenda, in which the negative image of business in conflicts, seen as fuelling, prolonging and taking commercial advantage of violent conflicts,still prevails. So far the scientific community has been reluctant to extend the scope of research on ‘corporate social responsibility’ to the area of security in general and to intra-state armed conflicts in particular. As a consequence, there is no basis from which systematic knowledge can be generated about the conditions and the extent to which private corporations can fulfil the role expected of them in the political discourse. The research on positive contributions of private corporations to security amounts to unconnected in-depth case studies of specific corporations in specific conflict settings. Given this state of research, we develop a framework for a comparative research agenda to address the question: Under which circumstances and to what extent can private corporations be expected to contribute to public security

Hemoglobin level is an independent predictor for adverse cardiovascular outcomes in women undergoing evaluation for chest pain Results from the National Heart, Lung, and Blood Institute women's ischemia syndrome evaluation study

AbstractObjectivesThis study was designed to investigate the relationship between hemoglobin level (Hgb) and adverse cardiovascular outcomes in women with suspected ischemia.BackgroundLow Hgb levels correlate with increased cardiovascular morbidity and mortality in patients presenting with acute myocardial infarction (MI) or congestive heart failure (CHF). However, the prognostic significance of Hgb in women with suspected ischemia is unclear.MethodsAs part of the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE), we prospectively studied 936 women referred for coronary angiography to evaluate suspected ischemia. We compared Hgb levels with cardiovascular risk factors, core lab interpreted angiograms, inflammatory markers, and adverse cardiovascular outcomes.ResultsOf women enrolled, 864 (mean age 58.4 ±11.6 years) had complete Hgb, angiogram, and follow-up (mean 3.3 ± 1.7 years) data. The mean Hgb was 12.9 g/dl (range 7.7 to 16.4 g/dl) and 184 women (21%) were anemic (Hgb <12 g/dl). Anemic women had higher creatinine and were more likely to be nonwhite and have a history of diabetes, hypertension, and CHF (p < 0.05). However, we found no difference in EF or severity of coronary artery disease. Anemic women had a higher risk of death from any cause (10.3% vs. 5.4%; p = 0.02) and total adverse outcomes (26% vs. 16%, p < 0.01). In a multivariable model, decreasing Hgb was associated with significantly higher risk of adverse outcomes (hazard ratio = 1.20, p = 0.002). Also, anemic women had shorter survival time free of adverse outcome (p < 0.001).ConclusionsOur findings extend previous reports, linking lower hemoglobin levels with higher risk for adverse cardiovascular outcomes, to women evaluated for suspected ischemia in the absence of acute MI or CHF

Small Molecule Inhibitors of Staphylococcus aureus RnpA Alter Cellular mRNA Turnover, Exhibit Antimicrobial Activity, and Attenuate Pathogenesis

Methicillin-resistant Staphylococcus aureus is estimated to cause more U.S. deaths annually than HIV/AIDS. The emergence of hypervirulent and multidrug-resistant strains has further amplified public health concern and accentuated the need for new classes of antibiotics. RNA degradation is a required cellular process that could be exploited for novel antimicrobial drug development. However, such discovery efforts have been hindered because components of the Gram-positive RNA turnover machinery are incompletely defined. In the current study we found that the essential S. aureus protein, RnpA, catalyzes rRNA and mRNA digestion in vitro. Exploiting this activity, high through-put and secondary screening assays identified a small molecule inhibitor of RnpA-mediated in vitro RNA degradation. This agent was shown to limit cellular mRNA degradation and exhibited antimicrobial activity against predominant methicillin-resistant S. aureus (MRSA) lineages circulating throughout the U.S., vancomycin intermediate susceptible S. aureus (VISA), vancomycin resistant S. aureus (VRSA) and other Gram-positive bacterial pathogens with high RnpA amino acid conservation. We also found that this RnpA-inhibitor ameliorates disease in a systemic mouse infection model and has antimicrobial activity against biofilm-associated S. aureus. Taken together, these findings indicate that RnpA, either alone, as a component of the RNase P holoenzyme, and/or as a member of a more elaborate complex, may play a role in S. aureus RNA degradation and provide proof of principle for RNA catabolism-based antimicrobial therapy

CST does not evict elongating telomerase but prevents initiation by ssDNA binding

The CST complex (CTC1-STN1-TEN1) has been shown to inhibit telomerase extension of the G-strand of telomeres and facilitate the switch to C-strand synthesis by DNA polymerase alpha-primase (pol α-primase). Recently the structure of human CST was solved by cryo-EM, allowing the design of mutant proteins defective in telomeric ssDNA binding and prompting the reexamination of CST inhibition of telomerase. The previous proposal that human CST inhibits telomerase by sequestration of the DNA primer was tested with a series of DNA-binding mutants of CST and modeled by a competitive binding simulation. The DNA-binding mutants had substantially reduced ability to inhibit telomerase, as predicted from their reduced affinity for telomeric DNA. These results provide strong support for the previous primer sequestration model. We then tested whether addition of CST to an ongoing processive telomerase reaction would terminate DNA extension. Pulse-chase telomerase reactions with addition of either wild-type CST or DNA-binding mutants showed that CST has no detectable ability to terminate ongoing telomerase extension in vitro. The same lack of inhibition was observed with or without pol α-primase bound to CST. These results suggest how the switch from telomerase extension to C-strand synthesis may occur

The complete genome sequence and comparative genome analysis of the high pathogenicity Yersinia enterocolitica strain 8081

The human enteropathogen, Yersinia enterocolitica, is a significant link in the range of Yersinia pathologies extending from mild gastroenteritis to bubonic plague. Comparison at the genomic level is a key step in our understanding of the genetic basis for this pathogenicity spectrum. Here we report the genome of Y. enterocolitica strain 8081 (serotype 0:8; biotype 1B) and extensive microarray data relating to the genetic diversity of the Y. enterocolitica species. Our analysis reveals that the genome of Y. enterocolitica strain 8081 is a patchwork of horizontally acquired genetic loci, including a plasticity zone of 199 kb containing an extraordinarily high density of virulence genes. Microarray analysis has provided insights into species-specific Y. enterocolitica gene functions and the intraspecies differences between the high, low, and nonpathogenic Y. enterocolitica biotypes. Through comparative genome sequence analysis we provide new information on the evolution of the Yersinia. We identify numerous loci that represent ancestral clusters of genes potentially important in enteric survival and pathogenesis, which have been lost or are in the process of being lost, in the other sequenced Yersinia lineages. Our analysis also highlights large metabolic operons in Y. enterocolitica that are absent in the related enteropathogen, Yersinia pseudotuberculosis, indicating major differences in niche and nutrients used within the mammalian gut. These include clusters directing, the production of hydrogenases, tetrathionate respiration, cobalamin synthesis, and propanediol utilisation. Along with ancestral gene clusters, the genome of Y. enterocolitica has revealed species-specific and enteropathogen-specific loci. This has provided important insights into the pathology of this bacterium and, more broadly, into the evolution of the genus. Moreover, wider investigations looking at the patterns of gene loss and gain in the Yersinia have highlighted common themes in the genome evolution of other human enteropathogens