Highly Constrained Intergenic Drosophila Ultraconserved Elements Are Candidate ncRNAs

Eukaryotes contain short (∼80–200 bp) regions that have few or no substitutions among species that represent hundreds of millions of years of evolutionary divergence. These ultraconserved elements (UCEs) are candidates for containing essential functions, but their biological roles remain largely unknown. Here, we report the discovery and characterization of UCEs from 12 sequenced Drosophilaspecies. We identified 98 elements ≥80 bp long with very high conservation across the Drosophila phylogeny. Population genetic analyses reveal that these UCEs are not present in mutational cold spots. Instead we infer that they experience a level of selective constraint almost 10-fold higher compared with missense mutations in protein-coding sequences, which is substantially higher than that observed previously for human UCEs. About one-half of these Drosophila UCEs overlap the transcribed portion of genes, with many of those that are within coding sequences likely to correspond to sites of ADAR-dependent RNA editing. For the remaining UCEs that are in nongenic regions, we find that many are potentially capable of forming RNA secondary structures. Among ten chosen for further analysis, we discovered that the majority are transcribed in multiple tissues of Drosophila melanogaster. We conclude that Drosophilaspecies are rich with UCEs and that many of them may correspond to novel noncoding RNAs

Transcript of The Dory Derby Accident

This story is an excerpt from a longer interview that was collected as part of the Launching through the Surf: The Dory Fleet of Pacific City project. In this story, Don Grotjohn recounts an accident that occurred during a Dory Derby competition

Functional conservation of the Drosophila hybrid incompatibility gene Lhr

<p>Abstract</p> <p>Background</p> <p>Hybrid incompatibilities such as sterility and lethality are commonly modeled as being caused by interactions between two genes, each of which has diverged separately in one of the hybridizing lineages. The gene <it>Lethal hybrid rescue </it>(<it>Lhr</it>) encodes a rapidly evolving heterochromatin protein that causes lethality of hybrid males in crosses between <it>Drosophila melanogaster </it>females and <it>D. simulans </it>males. Previous genetic analyses showed that hybrid lethality is caused by <it>D. simulans Lhr </it>but not by <it>D. melanogaster Lhr</it>, confirming a critical prediction of asymmetry in the evolution of a hybrid incompatibility gene.</p> <p>Results</p> <p>Here we have examined the functional properties of <it>Lhr </it>orthologs from multiple Drosophila species, including interactions with other heterochromatin proteins, localization to heterochromatin, and ability to complement hybrid rescue in <it>D. melanogaster</it>/<it>D. simulans </it>hybrids. We find that these properties are conserved among most <it>Lhr </it>orthologs, including <it>Lhr </it>from <it>D. melanogaster</it>, <it>D. simulans </it>and the outgroup species <it>D. yakuba</it>.</p> <p>Conclusions</p> <p>We conclude that evolution of the hybrid lethality properties of <it>Lhr </it>between <it>D. melanogaster </it>and <it>D. simulans </it>did not involve extensive loss or gain of functions associated with protein interactions or localization to heterochromatin.</p

Mammography Facility Characteristics Associated With Interpretive Accuracy of Screening Mammography

BackgroundAlthough interpretive performance varies substantially among radiologists, such variation has not been examined among mammography facilities. Understanding sources of facility variation could become a foundation for improving interpretive performance.MethodsIn this cross-sectional study conducted between 1996 and 2002, we surveyed 53 facilities to evaluate associations between facility structure, interpretive process characteristics, and interpretive performance of screening mammography (ie, sensitivity, specificity, positive predictive value [PPV1], and the likelihood of cancer among women who were referred for biopsy [PPV2]). Measures of interpretive performance were ascertained prospectively from mammography interpretations and cancer data collected by the Breast Cancer Surveillance Consortium. Logistic regression and receiver operating characteristic (ROC) curve analyses estimated the association between facility characteristics and mammography interpretive performance or accuracy (area under the ROC curve [AUC]). All P values were two-sided.ResultsOf the 53 eligible facilities, data on 44 could be analyzed. These 44 facilities accounted for 484 463 screening mammograms performed on 237 669 women, of whom 2686 were diagnosed with breast cancer during follow-up. Among the 44 facilities, mean sensitivity was 79.6% (95% confidence interval [CI] = 74.3% to 84.9%), mean specificity was 90.2% (95% CI = 88.3% to 92.0%), mean PPV1 was 4.1% (95% CI = 3.5% to 4.7%), and mean PPV2 was 38.8% (95% CI = 32.6% to 45.0%). The facilities varied statistically significantly in specificity (P &lt; .001), PPV1 (P &lt; .001), and PPV2 (P = .002) but not in sensitivity (P = .99). AUC was higher among facilities that offered screening mammograms alone vs those that offered screening and diagnostic mammograms (0.943 vs 0.911, P = .006), had a breast imaging specialist interpreting mammograms vs not (0.932 vs 0.905, P = .004), did not perform double reading vs independent double reading vs consensus double reading (0.925 vs 0.915 vs 0.887, P = .034), or conducted audit reviews two or more times per year vs annually vs at an unknown frequency (0.929 vs 0.904 vs 0.900, P = .018).ConclusionMammography interpretive performance varies statistically significantly by facility

Medical image colorization for better visualization and segmentation

Medical images contain precious anatomical information for clinical procedures. Improved understanding of medical modality may contribute significantly in arena of medical image analysis. This paper investigates enhancement of monochromatic medical modality into colorized images. Improving the contrast of anatomical structures facilitates precise segmentation. The proposed framework starts with pre-processing to remove noise and improve edge information. Then colour information is embedded to each pixel of a subject image. A resulting image has a potential to portray better anatomical information than a conventional monochromatic image. To evaluate the performance of colorized medical modality, the structural similarity index and the peak signal to noise ratio are computed. Supremacy of proposed colorization is validated by segmentation experiments and compared with greyscale monochromatic images

The effect of tobacco smoking and treatment strategy on the one-year mortality of patients with acute non-ST-segment elevation myocardial infarction

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to investigate whether a previously shown survival benefit resulting from routine early invasive management of unselected patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) may differ according to smoking status and age.</p> <p>Methods</p> <p>Post-hoc analysis of a prospective observational cohort study of consecutive patients admitted for NSTEMI in 2003 (conservative strategy cohort [CS]; n = 185) and 2006 (invasive strategy cohort [IS]; n = 200). A strategy for transfer to a high-volume invasive center and routine early invasive management was implemented in 2005. Patients were subdivided into current smokers and non-smokers (including ex-smokers) on admission.</p> <p>Results</p> <p>The one-year mortality rate of smokers was reduced from 37% in the CS to 6% in the IS (p < 0.001), and from 30% to 23% for non-smokers (p = 0.18). Non-smokers were considerably older than smokers (median age 80 vs. 63 years, p < 0.001). The percentage of smokers who underwent revascularization (angioplasty or coronary artery bypass grafting) within 7 days increased from 9% in the CS to 53% in the IS (p < 0.001). The corresponding numbers for non-smokers were 5% and 27% (p < 0.001). There was no interaction between strategy and age (p = 0.25), as opposed to a significant interaction between strategy and smoking status (p = 0.024). Current smoking was an independent predictor of one-year mortality (hazard ratio 2.61, 95% confidence interval 1.43-4.79, p = 0.002).</p> <p>Conclusions</p> <p>The treatment effect of an early invasive strategy in unselected patients with NSTEMI was more pronounced among smokers than non-smokers. The benefit for smokers was not entirely explained by differences in baseline confounders, such as their younger age.</p

Heterochromatin: A Rapidly Evolving Species Barrier

Recent work has shown that changes in the sequence composition of heterochromatin, or in the factors that maintain that heterochromatin, may play an important role in speciation

The "smoker's paradox" in patients with acute coronary syndrome: a systematic review

<p>Abstract</p> <p>Background</p> <p>Smokers have been shown to have lower mortality after acute coronary syndrome than non-smokers. This has been attributed to the younger age, lower co-morbidity, more aggressive treatment and lower risk profile of the smoker. Some studies, however, have used multivariate analyses to show a residual survival benefit for smokers; that is, the "smoker's paradox". The aim of this study was, therefore, to perform a systematic review of the literature and evidence surrounding the existence of the "smoker's paradox".</p> <p>Methods</p> <p>Relevant studies published by September 2010 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1963) and the Cochrane Central Register of Controlled Trials, with a combination of text words and subject headings used. English-language original articles were included if they presented data on hospitalised patients with defined acute coronary syndrome, reported at least in-hospital mortality, had a clear definition of smoking status (including ex-smokers), presented crude and adjusted mortality data with effect estimates, and had a study sample of > 100 smokers and > 100 non-smokers. Two investigators independently reviewed all titles and abstracts in order to identify potentially relevant articles, with any discrepancies resolved by repeated review and discussion.</p> <p>Results</p> <p>A total of 978 citations were identified, with 18 citations from 17 studies included thereafter. Six studies (one observational study, three registries and two randomised controlled trials on thrombolytic treatment) observed a "smoker's paradox". Between the 1980s and 1990s these studies enrolled patients with acute myocardial infarction (AMI) according to criteria similar to the World Health Organisation criteria from 1979. Among the remaining 11 studies not supporting the existence of the paradox, five studies represented patients undergoing contemporary management.</p> <p>Conclusion</p> <p>The "smoker's paradox" was observed in some studies of AMI patients in the pre-thrombolytic and thrombolytic era, whereas no studies of a contemporary population with acute coronary syndrome have found evidence for such a paradox.</p

Recent physician strike in Israel: a health system under stress?

In 2011, a series of physician strikes in Israel followed eight months of unsuccessful negotiations with the government (Ministry of Health and the Ministry of Finance). Strikes by physicians may be a warning that all is not well in a health system and protestors have claimed that they signify a system failure. In contrast, others argue that strikes have been a feature of the Israeli health system from its inception and should not be a cause for alarm. This paper analyses the Israeli health system from the perspective of the strikers' demands using the World Health Organisation's six health system building blocks as a framework, including: service delivery; health workforce; information; medical products, vaccines and technologies; leadership and governance; and financing. While we recognise that the immediate causes of the 2011 strikes were concerns about salaries and working conditions, we argue that a complex set of interacting factors underlie the strikers' demands, resonating with issues relating to five of the WHO building blocks. We argue that of the five, three are most significant and limit progress with all the others: a disgruntled health workforce, many of whom believe that striking is the only way to be heard; a lack of leadership by the government in understanding and responding to physicians' concerns; and a purported information insufficiency, manifest as a lack of critique and analysis that may have prevented those at the top from making a reliable diagnosis of the system's problems. This paper argues that there are cracks within the Israeli health system but that these are not irresolvable. The Israeli health system is a relatively new and popular health system, but there are no grounds for complacency

Performance Benchmarks for Screening Mammography

PURPOSE: To retrospectively evaluate the range of performance outcomes of the radiologist in an audit of screening mammography by using a representative sample of U.S. radiologists to allow development of performance benchmarks for screening mammography. MATERIALS AND METHODS: Institutional review board approval was obtained, and study was HIPAA compliant. Informed consent was or was not obtained according to institutional review board guidelines. Data from 188 mammographic facilities and 807 radiologists obtained between 1996 and 2002 were analyzed from six registries from the Breast Cancer Surveillance Consortium (BCSC). Contributed data included demographic information, clinical findings, mammographic interpretation, and biopsy results. Measurements calculated were positive predictive values (PPVs) from screening mammography (PPV(1)), biopsy recommendation (PPV(2)), biopsy performed (PPV(3)), recall rate, cancer detection rate, mean cancer size, and cancer stage. Radiologist performance data are presented as 50th (median), 10th, 25th, 75th, and 90th percentiles and as graphic presentations by using smoothed curves. RESULTS: There were 2 580 151 screening mammographic studies from 1 117 390 women (age range, /=80 years). The respective means and ranges of performance outcomes for the middle 50% of radiologists were as follows: recall rate, 9.8% and 6.4%-13.3%; PPV(1), 4.8% and 3.4%-6.2%; and PPV(2), 24.6% and 18.8%-32.0%. Mean cancer detection rate was 4.7 per 1000, and the median [corrected] mean size of invasive cancers was 13 mm. The range of performance outcomes for the middle 80% of radiologists also was presented. CONCLUSION: Community screening mammographic performance measurements of cancer outcomes for the majority of radiologists in the BCSC surpass performance recommendations. Recall rate for almost half of radiologists, however, is higher than the recommended rate