Adverse Effects of Trichothiodystrophy DNA Repair and Transcription Gene Abnormalities on Human Fetal Development

The effects of DNA repair and transcription genes in human prenatal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10^-6^) recessive disorder caused by mutations in genes involved in the nucleotide excision repair (NER) pathway and in transcription. Based on our clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD-affected offspring (N=24) with respect to abnormalities in their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (N=18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD-affected pregnancies. Gestational complications were noted in nearly all pregnancies resulting in TTD-affected offspring with _XPD_ and _TTDN1_, but not _TTD-A_, gene mutations. Abnormal placental development may explain the constellation of observed complications; therefore, we hypothesize that some TTD genes play an important role in normal placental and fetal development. We investigated this hypothesis by analyzing the expression patterns of TTD genes. Expression of _TTDA_ was strongly negatively correlated (r=-0.7,P<0.0001) with gestational age, while _XPD, XPB_ and _TTDN1_ were consistently expressed from 14 to 40 weeks gestation. *Conclusion:* Our results indicate an important role for _XPD, XPB_ and _TTDN1_ gene products during normal human placental and fetal development

Feminist Geopolitics: Material States

No abstract available

Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I:A United States-Based Stepped-Wedge, Randomized Trial

STUDY OBJECTIVE: The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol.METHODS: The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI.RESULTS: There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68).CONCLUSION: A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.</p

Hard Science and Soft Interpersonal Skills

Carl Carter is a professional photographer who once worked as a grip in movies filmed in New York City. The job of the grip is to install the tracks upon which cameras are mounted and also performs other manual labor as needed on a movie set. Carl was hired many times by both Woody Allen and Sidney Lumet, directors and movie makers who filmed most of their movies in New York City. Allen and Lumet made movies that were very different. Allen is famous for light, romantic comedies, such as Annie Hall, Bullets over Broadway and Everybody says I Love You. Sidney Lumet’s movies are much darker and more dramatic. Among his most famous works are Twelve Angry Men, Dog Day Afternoon and Serpico

Using PLSI-U to Detect Insider Threats by Datamining Email

Despite a technology bias that focuses on external electronic threats, insiders pose the greatest threat to an organisation. This paper discusses an approach to assist investigators in identifying potential insider threats. We discern employees\u27 interests from e-mail using an extended version of PLSI. These interests are transformed into implicit and explicit social network graphs, which are used to locate potential insiders by identifying individuals who feel alienated from the organisation or have a hidden interest in a sensitive topic. By applying this technique to the Enron e-mail corpus, a small number of employees appear as potential insider threats

Genetic implications of reduced survival of male red deer \u3ci\u3eCervus elaphus\u3c/i\u3e under harvest

We use simple, multivariate evolutionary models to evaluate the short-term potential for size-selective harvest to reduce genetic variability and alter life history in cervids. These genetic effects limit sustainable levels of harvest of the animals because they determine how changes in sex ratio, generation length and traits contributing to fitness influence population growth rate and local adaptation. Our analysis of harvest-mediated adaptive evolution employs a genetic approach that parameterizes models with empirical data obtained from European red deer Cervus elaphus. The analysis indicates that harvest, if sufficiently high to reduce the breeding ratio of males to females to below about 15:100, can reduce effective population size to a level that threatens adaptive potential. The reduction in effective size is realized through decreases in both sex ratio of breeders and the age of breeding males. Predicted selective effects of harvest on body size indicates a weak potential to alter most life-history traits over 10 generations under two harvest scenarios; the patterns suggest that current modes of harvest are unlikely to produce substantial life-history changes in red deer over 10 or fewer generations unless the genetic influences on red deer traits are considerably higher than those predicted here. Nevertheless, male reproductive success is expected to decline detectably if male harvest rate is sufficiently high (\u3e30%). Collectively, our results imply that harvest methods should permit higher post-hunt male:female ratios (18:100 or higher) and ensure that a sufficient number of larger, older males survive the breeding season. The capacity of selective harvest to alter demography and life history depends heavily on the genetic covariance structure underlying variation in these traits, information that is unknown for many red deer populations. Prudent harvest management should therefore implement and monitor approaches to hunting that aim to conserve life-history variation; meanwhile, use of less selective methods can reduce the risk to long-term adaptive potential and may permit higher sustainable harvest rates

The search for architectural remains at the planter\u27s house and the slave settlement, Richmond Hill Plantation, Georgetown County, South Carolina

Research Manuscript Series No. 205. Published by the University of South Carolina. Institute of Archaeology and Anthropology.https://digitalcommons.coastal.edu/michie-reports/1032/thumbnail.jp

Long-term studies of hantavirus reservoir populations in the southwestern United States: rationale, potential, and methods.

Hantaviruses are rodent-borne zoonotic agents that cause hemorrhagic fever with renal syndrome in Asia and Europe and hantavirus pulmonary syndrome (HPS) in North and South America. The epidemiology of human diseases caused by these viruses is tied to the ecology of the rodent hosts, and effective control and prevention relies on a through understanding of host ecology. After the 1993 HPS outbreak in the southwestern United States, the Centers for Disease Control and Prevention initiated long-term studies of the temporal dynamics of hantavirus infection in host populations. These studies, which used mark-recapture techniques on 24 trapping webs at nine sites in the southwestern United States, were designed to monitor changes in reservoir population densities and in the prevalence and incidence of infection; quantify environmental factors associated with these changes; and when linked to surveillance databases for HPS, lead to predictive models of human risk to be used in the design and implementation of control and prevention measures for human hantavirus disease

Sequence Pattern Mining with Variables

Sequence pattern mining (SPM) seeks to find multiple items that commonly occur together in a specific order. One common assumption is that all of the relevant differences between items are captured through creating distinct items, e.g., if color matters then the same item in two different colors would have two items created, one for each color. In some domains, that is unrealistic. This paper makes two contributions. The first extends SPM algorithms to allow item differentiation through attribute variables for domains with large numbers of items, e.g, by having one item with a variable with a color attribute rather than distinct items for each color. It demonstrates this by incorporating variables into Discontinuous Varied Order Sequence Mining (DVSM). The second contribution is the creation of Sequence Mining of Temporal Clusters (SMTC), a new SPM that addresses the interleaving issue common to SPM algorithms. Most SPM algorithms address interleaving by using a distance measure to separate co-occurring sequences. SMTC addresses interleaving by clustering all subsets of temporally close items and deferring the sequencing of mined patterns until the entire dataset if examined. Evaluation of the SPM algorithms on a digital forensics media analysis task results in a 96% reduction in terms to review, 100% detection of true positives and no false positives