Sample records for identify previously unrecognized

  1. Previously Unrecognized Large Lunar Impact Basins Revealed by Topographic Data

    NASA Technical Reports Server (NTRS)

    Frey, Herbert V.

    2008-01-01

    The discovery of a large population of apparently buried impact craters on Mars, revealed as Quasi- Circular Depressions (QCDs) in Mars Orbiting Laser Altimeter (MOLA) data [1,2,3] and as Circular Thin Areas (CTAs) [4] in crustal thickness model data [5] leads to the obvious question: are there unrecognized impact features on the Moon and other bodies in the solar system? Early analysis of Clementine topography revealed several large impact basins not previously known [6,7], so the answer certainly is "Yes." How large a population of previously undetected impact basins, their size frequency distribution, and how much these added craters and basins will change ideas about the early cratering history and Late Heavy Bombardment on the Moon remains to be determined. Lunar Orbiter Laser Altimeter (LOLA) data [8] will be able to address these issues. As a prelude, we searched the state-of-the-art global topographic grid for the Moon, the Unified Lunar Control Net (ULCN) [9] for evidence of large impact features not previously recognized by photogeologic mapping, as summarized by Wilhelms [lo].

  2. Evidence for a previously unrecognized species of owlet-nightjar

    USGS Publications Warehouse

    Pratt, T.K.

    2000-01-01

    I studied the systematic relationships of the three large owlet-nightjars (Aegothelidae) to determine the taxonomic status of a fawn-colored lowland form currently classified as Aegotheles insignis tatei. I examined most of the existing specimens of A. i. insignis (n = 158) and A. crinifrons (n = 23) and all known specimens of A. i. tatei (n = 4). I also examined specimens of A. albertisi (n = 70), A. archboldi (n = 25), A. bennettii (n = 55), A. cristatus (n = 50), A. savesi (n = 1), and A. wallacii (n = 21). Aegotheles i. tatei was distinguishable from A. i. insignis and A. crinifrons by its small size and in seven plumage characters. Aegotheles i. tatei was further distinguishable from one or the other of these taxa by four additional characters. Unique among owlet-nightjars, A. i. tatei has the shortest tarsi, does not have recurved filamentous tips on its facial feathers, and has stiffer feathers on the auricular area and throat. My search of museums revealed two new specimens of A. i. tatei, expanding the known geographic range of this taxon 1,000 km eastward along the southern coast of Papua New Guinea from the upper Fly River to Nunumai, near the Ulamanu River. Unlike the montane A. i. insignis, A. i. tatei inhabits lowland forests where rivers emerge from foothills of the main cordillera. I propose that tatei be elevated to species status and that the name Starry Owlet-Nightjar be adopted based on the bird's markings. Aegotheles crinifrons, A. insignis, and A. tatei pass through a previously unrecognized but distinctive rufous juvenal plumage. These are the only owlet-nightjars known to exhibit this plumage, which calls for reexamination of generic limits within the Aegothelidae.

  3. Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease.

    PubMed

    Kumar, Manoj; Sharma, Barjesh C; Sarin, Shiv K

    2008-06-01

    Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001). During

  4. New technologies, human-microbe interactions, and the search for previously unrecognized pathogens.

    PubMed

    Relman, David A

    2002-12-01

    Evidence suggests that a significant number of clinically important microbial pathogens remain unrecognized. Observations from the natural world, from patterns of disease in human populations, from the bedside, and from the clinical laboratory all contribute to this body of evidence. A variety of acute and chronic neurologic syndromes illustrate this point; despite features of infection, most cases of aseptic meningitis, encephalitis, and cerebral vasculitis cannot be assigned a microbiologic diagnosis. The development and clinical application of molecular methods have led to the discovery of novel members of the endogenous normal flora as well as putative disease agents. Current challenges include the establishment of criteria for disease causation and further characterization of the human microbiome during states of health. These challenges and the goal of understanding microbial contributions to inflammatory disease may be addressed effectively through the thoughtful integration of modern technologies and clinical insight.

  5. Prevalence and Significance of Unrecognized Lower Extremity Peripheral Arterial Disease in General Medicine Practice

    PubMed Central

    McGrae McDermott, Mary; Kerwin, Diana R; Liu, Kiang; Martin, Gary J; O'Brien, Erin; Kaplan, Heather; Greenland, Philip

    2001-01-01

    OBJECTIVE To determine the prevalence of unrecognized lower extremity peripheral arterial disease (PAD) among men and women aged 55 years and older in a general internal medicine (GIM) practice and to identify characteristics and functional performance associated with unrecognized PAD. DESIGN Cross-sectional. SETTING Academic medical center. PARTICIPANTS We identified 143 patients with known PAD from the noninvasive vascular laboratory, and 239 men and women aged 55 and older with no prior PAD history from a GIM practice. Group 1 consisted of patients with PAD consecutively identified from the noninvasive vascular laboratory (n = 143). Group 2 included GIM practice patients found to have an ankle brachial index less than 0.90, consistent with PAD (n = 34). Group 3 consisted of GIM practice patients without PAD (n = 205). MEASUREMENTS AND MAIN RESULTS Leg functioning was assessed with the 6-minute walk, 4-meter walking velocity, and Walking Impairment Questionnaire (WIQ). Of GIM practice patients, 14% had unrecognized PAD. Only 44% of patients in Group 2 had exertional leg symptoms. Distances achieved in the 6-minute walk were 1,130, 1,362, and 1,539 feet for Groups 1, 2, and 3, respectively, adjusting for age, gender, and race (P < .001). The degree of difficulty walking due to leg symptoms as reported on the WIQ was comparable between Groups 2 and 3 and significantly greater in Group 1 than Group 2. In multiple logistic regression analysis including Groups 2 and 3, current cigarette smoking was associated independently with unrecognized PAD (odds ratio [OR], 6.82; 95% confidence interval [95% CI], 1.55 to 29.93). Aspirin therapy was nearly independently associated with absence of PAD (OR, 0.37; 95% CI, 0.12 to 1.12). CONCLUSION Unrecognized PAD is common among men and women aged 55 years and older in GIM practice and is associated with impaired lower extremity functioning. Ankle brachial index screening may be necessary to diagnose unrecognized PAD in a GIM

  6. Quid est Clea helena? Evidence for a previously unrecognized radiation of assassin snails (Gastropoda: Buccinoidea: Nassariidae)

    PubMed Central

    Galindo, Lee Ann; Kantor, Yuri I.

    2017-01-01

    The genus Clea from SE Asia is from one of only two unrelated families among the megadiverse predatory marine Neogastropoda to have successfully conquered continental waters. While little is known about their anatomy, life history and ecology, interest has grown exponentially in recent years owing to their increasing popularity as aquarium pets. However, the systematic affinities of the genus and the validity of the included species have not been robustly explored. Differences in shell, operculum and radula characters support separation of Clea as presently defined into two distinct genera: Clea, for the type species Clea nigricans and its allies, and Anentome for Clea helena and allies. A five-gene mitochondrial (COI, 16S, 12S) and nuclear (H3, 28S) gene dataset confirms the placement of Anentome as a somewhat isolated offshoot of the family Nassariidae and sister to the estuarine Nassodonta. Anatomical data corroborate this grouping and, in conjunction with their phylogenetic placement, support their recognition as a new subfamily, the Anentominae. The assassin snail Anentome helena, a popular import through the aquarium trade so named for their voracious appetite for other snails, is found to comprise a complex of at least four species. None of these likely represents true Anentome helena described from Java, including a specimen purchased through the aquarium trade under this name in the US and one that was recently found introduced in Singapore, both of which were supported as conspecific with a species from Thailand. The introduction of Anentome “helena” through the aquarium trade constitutes a significant threat to native aquatic snail faunas which are often already highly imperiled. Comprehensive systematic revision of this previously unrecognized species complex is urgently needed to facilitate communication and manage this emerging threat. PMID:28828249

  7. Misleading hallucinations in unrecognized narcolepsy.

    PubMed

    Szucs, A; Janszky, J; Holló, A; Migléczi, G; Halász, P

    2003-10-01

    To describe psychosis-like hallucinatory states in unrecognized narcolepsy. Two patients with hypnagogic/hypnapompic hallucinations are presented. Both patients had realistic and complex - multi-modal and scenic-daytime sexual hallucinations leading, in the first case, to a legal procedure because of false accusation, and in the second, to serious workplace conflicts. Both patients were convinced of the reality of their hallucinatory experiences but later both were able to recognize their hallucinatory character. Clinical data, a multiple sleep latency test, polysomnography, and HLA typing revealed that both patients suffered from narcolepsy. We suggest that in unrecognized narcolepsy with daytime hypnagogic/hypnapompic hallucinations the diagnostic procedure may mistakenly incline towards delusional psychoses. Daytime realistic hypnagogic/hypnapompic hallucinations may also have forensic consequences and mislead legal evaluation. Useful clinical features in differentiating narcolepsy from psychoses are: the presence of other narcoleptic symptoms, features of hallucinations, and response to adequate medication.

  8. Identification of unrecognized tundra fire events on the north slope of Alaska

    USGS Publications Warehouse

    Jones, Benjamin M.; Breen, Amy L.; Gaglioti, Benjamin V.; Mann, Daniel H.; Rocha, Adrian V.; Grosse, Guido; Arp, Christopher D.; Kunz, Michael L.; Walker, Donald A.

    2013-01-01

    Characteristics of the natural fire regime are poorly resolved in the Arctic, even though fire may play an important role cycling carbon stored in tundra vegetation and soils to the atmosphere. In the course of studying vegetation and permafrost-terrain characteristics along a chronosequence of tundra burn sites from AD 1977, 1993, and 2007 on the North Slope of Alaska, we discovered two large, previously unrecognized tundra fires. The Meade River fire burned an estimated 500 km2 and the Ketik River fire burned an estimated 1200 km2. Based on radiocarbon dating of charred twigs, analysis of historic aerial photography, and regional climate proxy data, these fires likely occurred between AD 1880 and 1920. Together, these events double the estimated burn area on the North Slope of Alaska over the last ~100 to 130 years. Assessment of vegetation succession along the century-scale chronosequence of tundra fire disturbances demonstrates for the first time on the North Slope of Alaska that tundra fires can facilitate the invasion of tundra by shrubs. Degradation of ice-rich permafrost was also evident at the fire sites and likely aided in the presumed changes of the tundra vegetation postfire. Other previously unrecognized tundra fire events likely exist in Alaska and other Arctic regions and identification of these sites is important for better understanding disturbance regimes and carbon cycling in Arctic tundra.

  9. The impact of unrecognized autoimmune rheumatic diseases on the incidence of preeclampsia and fetal growth restriction: a longitudinal cohort study.

    PubMed

    Spinillo, Arsenio; Beneventi, Fausta; Locatelli, Elena; Ramoni, Vèronique; Caporali, Roberto; Alpini, Claudia; Albonico, Giulia; Cavagnoli, Chiara; Montecucco, Carlomaurizio

    2016-10-18

    The burden of pregnancy complications associated with well defined, already established systemic rheumatic diseases preexisting pregnancy such as rheumatoid arthritis, systemic lupus erythematosus or scleroderma is well known. Systemic rheumatic diseases are characterized by a long natural history with few symptoms, an undifferentiated picture or a remitting course making difficult a timely diagnosis. It has been suggested that screening measures for these diseases could be useful but the impact of unrecognized systemic rheumatic disorders on pregnancy outcome is unknown. The objective of the study was to evaluate the impact of previously unrecognized systemic autoimmune rheumatic on the incidence of preeclampsia and fetal growth restriction (FGR). A longitudinal cohort-study with enrolment during the first trimester of pregnancy of women attending routine antenatal care using a two-step approach with a self-reported questionnaire, autoantibody detection and clinical evaluation of antibody-positive subjects. The incidence of FGR and preeclampsia in subjects with newly diagnosed rheumatic diseases was compared to that of selected negative controls adjusting for potential confounders by logistic regression analysis. The prevalence of previously unrecognized systemic rheumatic diseases was 0.4 % for rheumatoid arthritis (19/5232), 0.25 % (13/5232) for systemic lupus erythematosus, 0.31 % (16/5232) for Sjögren's syndrome, 0.3 % for primary antiphospholipid syndrome (14/5232) and 0.11 % (6/5232) for other miscellaneous diseases. Undifferentiated connective tissue disease was diagnosed in an additional 131 subjects (2.5 %). The incidence of either FGR or preeclampsia was 6.1 % (36/594) among controls and 25.3 % (50/198) in subjects with unrecognized rheumatic diseases (excess incidence = 3.9 % (95 % CI = 2.6-9.6) or 34 % (95 % CI = 22-44) of all cases of FGR/preeclampsia). The incidence of small for gestational age infant (SGA) was higher among

  10. Persistently high prevalence and unrecognized HIV infection among men who have sex with men in Baltimore: the BESURE Study

    PubMed Central

    German, Danielle; Sifakis, Frangiscos; Maulsby, Cathy; Towe, Vivian L.; Flynn, Colin P.; Latkin, Carl A.; Celentano, David D.; Hauck, Heather; Holtgrave, David R.

    2017-01-01

    Background Given high rates of HIV among Baltimore MSM, we examined characteristics associated with HIV prevalence and unrecognized HIV infection among Baltimore MSM at two time points. Methods Cross-sectional behavioral surveys and HIV testing in 2004–2005 and 2008 using venue-based sampling among adult Baltimore men at MSM-identified locations. MSM was defined as sex with a male partner in the past year. Bivariate and backwards stepwise regression identified characteristics associated with HIV and unrecognized infection. Findings HIV prevalence was 37.7% overall in 2004–2005 (n=645) and 37.5% in 2008 (n=448), 51.4% and 44.7% among Black MSM, and 12.9% and 18.3% among non-Hispanic White MSM. Compared to non-Hispanic White MSM, Black MSM were 4.0 times (95% C.I.: 2.3, 7.0) more likely to be HIV-positive in 2004–2005 and 2.5 times (95% C.I.: 1.5, 4.0) more likely in 2008. Prevalence of unrecognized HIV infection was 58.4% overall in 2004–2005 and 74.4% in 2008, 63.8% and 76.9% among Black MSM, and 15.4% and 47.4% among non-Hispanic White MSM. In adjusted models, unrecognized infection was significantly associated with minority race/ethnicity, younger age, and no prior year doctor visits in 2004–5 and with younger age and no prior year doctor visits in 2008. Conclusion High rates of HIV infection and substantial rates of unrecognized HIV infection among Baltimore MSM, particularly men of color and young men, require urgent public and private sector attention and increased prevention response. PMID:21297479

  11. Unrecognized pediatric and adult family members of children with acute brucellosis.

    PubMed

    Çiftdoğan, Dilek Yılmaz; Aslan, Selda

    Brucellosis is an infectious, contagious and zoonotic disease that occurs worldwide. The family members of an index case of brucellosis may be especially susceptible, due to sharing the same source of infection and similar risk factors for brucellosis. In this study, we propose to screen pediatric and adult family members of brucellosis index cases for detecting additional unrecognized infected family members. 114 family members of 41 pediatric patients with brucellosis were evaluated. All family members completed a brief questionnaire and were tested by a standard tube agglutination test (STA). The majority of family members (n=96, 84.2%) were children. Among the 114 family members, 42 (36.8%) were seropositive, and 15 (35.7%) were symptomatic. The majority of the symptomatic seropositive family members (n=12, 80%) had STA titers (≥1:640) higher than asymptomatic seropositive family members (n=9, 33%; p=0.004). The routine screening of both pediatric and adult family members of index cases is a priority in endemic areas. Using this screening approach, unrecognized family members who are seropositive for brucellosis will be identified earlier and be able to receive prompt treatment. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  12. A single macrolichen constitutes hundreds of unrecognized species.

    PubMed

    Lücking, Robert; Dal-Forno, Manuela; Sikaroodi, Masoumeh; Gillevet, Patrick M; Bungartz, Frank; Moncada, Bibiana; Yánez-Ayabaca, Alba; Chaves, José Luis; Coca, Luis Fernando; Lawrey, James D

    2014-07-29

    The number of Fungi is estimated at between 1.5 and 3 million. Lichenized species are thought to make up a comparatively small portion of this figure, with unrecognized species richness hidden among little-studied, tropical microlichens. Recent findings, however, suggest that some macrolichens contain a large number of unrecognized taxa, increasing known species richness by an order of magnitude or more. Here we report the existence of at least 126 species in what until recently was believed to be a single taxon: the basidiolichen fungus Dictyonema glabratum, also known as Cora pavonia. Notably, these species are not cryptic but morphologically distinct. A predictive model suggests an even larger number, with more than 400 species. These results call into question species concepts in presumably well-known macrolichens and demonstrate the need for accurately documenting such species richness, given the importance of these lichens in endangered ecosystems such as paramos and the alarming potential for species losses throughout the tropics.

  13. A single macrolichen constitutes hundreds of unrecognized species

    PubMed Central

    Lücking, Robert; Dal-Forno, Manuela; Sikaroodi, Masoumeh; Gillevet, Patrick M.; Bungartz, Frank; Moncada, Bibiana; Yánez-Ayabaca, Alba; Chaves, José Luis; Coca, Luis Fernando; Lawrey, James D.

    2014-01-01

    The number of Fungi is estimated at between 1.5 and 3 million. Lichenized species are thought to make up a comparatively small portion of this figure, with unrecognized species richness hidden among little-studied, tropical microlichens. Recent findings, however, suggest that some macrolichens contain a large number of unrecognized taxa, increasing known species richness by an order of magnitude or more. Here we report the existence of at least 126 species in what until recently was believed to be a single taxon: the basidiolichen fungus Dictyonema glabratum, also known as Cora pavonia. Notably, these species are not cryptic but morphologically distinct. A predictive model suggests an even larger number, with more than 400 species. These results call into question species concepts in presumably well-known macrolichens and demonstrate the need for accurately documenting such species richness, given the importance of these lichens in endangered ecosystems such as paramos and the alarming potential for species losses throughout the tropics. PMID:24982168

  14. Functional Metagenomics Reveals Previously Unrecognized Diversity of Antibiotic Resistance Genes in Gulls

    PubMed Central

    Martiny, Adam C.; Martiny, Jennifer B. H.; Weihe, Claudia; Field, Andrew; Ellis, Julie C.

    2011-01-01

    Wildlife may facilitate the spread of antibiotic resistance (AR) between human-dominated habitats and the surrounding environment. Here, we use functional metagenomics to survey the diversity and genomic context of AR genes in gulls. Using this approach, we found a variety of AR genes not previously detected in gulls and wildlife, including class A and C β-lactamases as well as six tetracycline resistance gene types. An analysis of the flanking sequences indicates that most of these genes are present in Enterobacteriaceae and various Gram-positive bacteria. In addition to finding known gene types, we detected 31 previously undescribed AR genes. These undescribed genes include one most similar to an uncharacterized gene in Verrucomicrobium and another to a putative DNA repair protein in Lactobacillus. Overall, the study more than doubled the number of clinically relevant AR gene types known to be carried by gulls or by wildlife in general. Together with the propensity of gulls to visit human-dominated habitats, this high diversity of AR gene types suggests that gulls could facilitate the spread of AR. PMID:22347872

  15. Small and large vessel disease in persons with unrecognized compared to recognized myocardial infarction: The Tromsø Study 2007-2008.

    PubMed

    Øhrn, Andrea Milde; Schirmer, Henrik; von Hanno, Therese; Mathiesen, Ellisiv B; Arntzen, Kjell Arne; Bertelsen, Geir; Njølstad, Inger; Løchen, Maja-Lisa; Wilsgaard, Tom; Bairey Merz, C Noel; Lindekleiv, Haakon

    2018-02-15

    Unrecognized myocardial infarction (MI) is a frequent condition with unknown underlying reason. We hypothesized the lack of recognition of MI is related to pathophysiology, specifically differences in underlying small and large vessel disease. 6128 participants were examined with retinal photography, ultrasound of the carotid artery and a 12‑lead electrocardiography (ECG). Small vessel disease was defined as narrower retinal arterioles and/or wider retinal venules measured on retinal photographs. Large vessel disease was defined as carotid artery pathology. We defined unrecognized MI as ECG-evidence of MI without a clinically recognized event. We analyzed the cross-sectional relationship between MI recognition and markers of small and large vessel disease, adjusted for age and sex. Unrecognized MI was present in 502 (8.2%) and recognized MI in 326 (5.3%) of the 6128 participants. Compared to recognized MI, unrecognized MI was associated with small vessel disease indicated by narrower retinal arterioles (OR 1.66, 95% CI 1.05-2.62, highest vs. lowest quartile). Unrecognized MI was less associated with wider retinal venules (OR 0.55, 95% CI 0.35-0.87, lowest vs. highest quartile). Compared to recognized MI, unrecognized MI was less associated with large vessel disease indicated by presence of plaque in the carotid artery (OR for presence of carotid artery plaque in unrecognized MI 0.51, 95% CI 0.37-0.69). No significant sex interaction was present. Unrecognized MI was more associated with small vessel disease and less associated with large vessel disease compared to recognized MI. These findings suggest that the pathophysiology behind unrecognized and recognized MI may differ. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  16. Unrecognized Fibrinogen A α-Chain Amyloidosis: Results From Targeted Genetic Testing.

    PubMed

    Tavares, Isabel; Oliveira, João Paulo; Pinho, Ana; Moreira, Luciana; Rocha, Liliana; Santos, Josefina; Pinheiro, Joaquim; Costa, Paulo Pinho; Lobato, Luísa

    2017-08-01

    Fibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases. Case series. 3 groups of participants: (1) kidney biopsy registry, n=4; (2) hemodialysis facility, n=122 of 267 patients; and (3) genetically at-risk individuals; n=69 of 167 family members. Kidney disease, kidney disease progression, and survival. The p.Glu545Val variant was identified in all 4 patients of the biopsy registry, 12 of 122 (9.8%) hemodialysis patients tested, and 34 of 69 (49%) relatives tested. These 50 cases belonged to 13 unrelated families with kidney disease or amyloidosis identified in 61% of probands. 35 individuals presented with hypertension at a mean of 51.0±10.4 years. Of these, 30 developed kidney disease at a mean of 56.7±12.0 years, and 21 initiated dialysis therapy at a mean of 61.4±11.3 years. Heart, liver, spleen, colon, and ileum were involved along the progression of the disease. Kidney disease was formerly attributed to hypertension in 25% of patients with AFib amyloidosis undergoing hemodialysis. Retrospective data collection for patients with amyloidosis previously diagnosed. AFib amyloidosis appears to be an under-recognized disorder in Braga, Portugal, where we found a high frequency of the FGA p.Glu545Val variant. Due to the nonspecific nature of its major clinical features, the diagnosis of AFib amyloidosis should have a high index of suspicion, particularly in populations in which hypertension is prevalent. Copyright © 2017

  17. Prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in southwest China

    PubMed Central

    Liu, Ya; Hu, Rong; Ouyang, Ling-yun; Liu, Jian-xiong; Li, Xiu-jun; Yi, Yan-jing; Wang, Tzung-Dau; Zhao, Shui-ping

    2017-01-01

    This study aimed to assess the prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in Southwest China. From September 2013 to March 2014, a cross-sectional survey was conducted in 4021 hypertensive patients aged 40 to 79 years living in Chengdu and Chongqing, China. Fasting plasma glucose (FPG) and 2h plasma glucose (2-hPG) in an oral glucose-tolerance test (OGTT) were used for assessments. Whether the patients previously had diabetes (DM) was determined by their own reports. The survey was carried out by the same questionnaire for all respondents. DM prevalence was 32.0% in hypertensive patients aged 40 to 79 years in Southwest China, with the rates of 29.6% and 33.5% in men and women, respectively (P<0.001). DM prevalence increased with age age and body-mass index. DM prevalence rates were 16.9%, 24.7%, 38.2% and 41.9% in hypertensive patients aged 40–49, 50–59, 60–69 and over 70, respectively. DM prevalence were 30.6%, 27.9%, 37.1%, and 37.4%, for BMI<18.5, 18.5–24.9, 25.0–29.9, and ≥30, respectively. Prevalence of unrecognized DM were 20.8% in hypertensive patients aged 40 to 79 years in Southwest China. Using only fasting blood glucose testing without OGTT would have resulted in 65.0% of missed DM diagnosis in these newly diagnosed patients. The prevalence of DM and unrecognized DM were high in hypertensive patients aged 40 to 79 years in Southwest China.These findings indicate that hypertensive patients aged 40 to 79 years should regularly submit to community-based OGTT screening for timely DM diagnosis. PMID:28192474

  18. Clinically unrecognized miliary tuberculosis: an autopsy study.

    PubMed

    Savic, Ivana; Trifunovic-Skodric, Vesna; Mitrovic, Dragan

    2016-01-01

    Miliary tuberculosis (TB) usually presents with atypical clinical manifestations; thus it is often recognized only at autopsy. Our objectives were to study the frequency of MT diagnosed at autopsy and determine clinical diagnoses that masked TB, as well as causes of death and comorbidities. Retrospective study of all autopsies performed between 2008 and 2014. Institute of Pathology, Belgrade, Serbia. in subjects where autopsy showed the presence of MT that was not recognized clinically, we recorded the clinical diagnoses (presumed causes of death) as reported in autopsy request forms, as well as actual cause of death and comorbidities as determined at autopsy. Clinically unrecognized MT. The total number of autopsies in this period was 6206. thirty-five individuals showed clinically unrecognized MT (0.56% of all autopsies, age: 62.2 [17.2] years, M:F=2:3). Common clinical diagnoses masking pulmonary MT were exacerbation of COPD (25%) and pulmonary thromboembolism (25%), with common radiological presentation of diffuse pulmonary infiltrates (56.3%). Dominant clinical diagnoses in patients with generalized MT were adult respiratory distress syndrome, sepsis, gastrointestinal bleeding and meningoencephalitis. Disseminated MT was often associated with secondary anemia or thrombocytopenia (15.8%) and recent surgery (15.8%). Frequent comorbidities included chronic renal failure and malignancies, whereas MT was a dominant cause of death. Greater awareness of MT is needed to improve recognition in clinical settings. In particular, MT should be considered in patients with atypical clinical presentation and diffuse pulmonary infiltrates on chest X-ray, particularly if they have chronic renal failure, malignancy, hematological disorders or a history of recent surgery. None.

  19. Unrecognized heart failure and chronic obstructive pulmonary disease (COPD) in frail elderly detected through a near-home targeted screening strategy.

    PubMed

    van Mourik, Yvonne; Bertens, Loes C M; Cramer, Maarten J M; Lammers, Jan-Willem J; Reitsma, Johannes B; Moons, Karel G M; Hoes, Arno W; Rutten, Frans H

    2014-01-01

    Reduced exercise tolerance and dyspnea are common in older people, and heart failure (HF) and chronic obstructive pulmonary disease (COPD) are the main causes. We want to determine the prevalence of previously unrecognized HF, COPD, and other chronic diseases in frail older people using a near-home targeted screening strategy. Community-dwelling frail persons aged ≥65 years underwent a 2-step screening strategy. First, they received a questionnaire inquiring about dyspnea and exercise tolerance. Those with exercise intolerance and/or dyspnea were invited to visit their primary care physician's office for a screening program, including medical history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. The final diagnosis of every patient was determined by a panel consisting of 3 physicians. Of the 570 elderly who filled out the questionnaire, 395 (69%) had reduced exercise tolerance or dyspnea. Of these, 389 underwent the screening program: 127 (33.5%, 95% confidence interval, 28.9-38.4%) were newly diagnosed with HF (mainly HF with a preserved ejection fraction [23.5%]), and previously unrecognized COPD was detected in 16.8% (95% confidence interval, 13.4-20.9%). In total, 165 patients (43.9%) received a new diagnosis of either HF, COPD, or both. Other new diagnoses (in 32.7% of the screening program patients) included atrial fibrillation (1.8%), valvular disease (21.4%), (persisting) asthma (3.1%), anemia (12.7%), and thyroid disease (0.6%). No clear explanation for the complaints of 47 patients (12.2%) was found using our strategy. Unrecognized chronic diseases might be detected in community-dwelling frail elderly using a near-home screening strategy that is simple to implement. It remains to be proven, however, whether optimizing treatment of the newly detected diagnoses in this fragile population with multimorbidities and polypharmacy improves quality of life and reduces morbidity and mortality. © Copyright 2014

  20. The evolution of avian wing shape and previously unrecognized trends in covert feathering

    PubMed Central

    Wang, Xia; Clarke, Julia A.

    2015-01-01

    Avian wing shape has been related to flight performance, migration, foraging behaviour and display. Historically, linear measurements of the feathered aerofoil and skeletal proportions have been used to describe this shape. While the distribution of covert feathers, layered over the anterior wing, has long been assumed to contribute to aerofoil properties, to our knowledge no previous studies of trends in avian wing shape assessed their variation. Here, these trends are explored using a geometric–morphometric approach with landmarks describing the wing outline as well as the extent of dorsal and ventral covert feathers for 105 avian species. We find that most of the observed variation is explained by phylogeny and ecology but shows only a weak relationship with previously described flight style categories, wing loading and an investigated set of aerodynamic variables. Most of the recovered variation is in greater primary covert feather extent, followed by secondary feather length and the shape of the wing tip. Although often considered a plastic character strongly linked to flight style, the estimated ancestral wing morphology is found to be generally conservative among basal parts of most major avian lineages. The radiation of birds is characterized by successive diversification into largely distinct areas of morphospace. However, aquatic taxa show convergence in feathering despite differences in flight style, and songbirds move into a region of morphospace also occupied by basal taxa but at markedly different body sizes. These results have implications for the proposed inference of flight style in extinct taxa. PMID:26446812

  1. The evolution of avian wing shape and previously unrecognized trends in covert feathering.

    PubMed

    Wang, Xia; Clarke, Julia A

    2015-10-07

    Avian wing shape has been related to flight performance, migration, foraging behaviour and display. Historically, linear measurements of the feathered aerofoil and skeletal proportions have been used to describe this shape. While the distribution of covert feathers, layered over the anterior wing, has long been assumed to contribute to aerofoil properties, to our knowledge no previous studies of trends in avian wing shape assessed their variation. Here, these trends are explored using a geometric-morphometric approach with landmarks describing the wing outline as well as the extent of dorsal and ventral covert feathers for 105 avian species. We find that most of the observed variation is explained by phylogeny and ecology but shows only a weak relationship with previously described flight style categories, wing loading and an investigated set of aerodynamic variables. Most of the recovered variation is in greater primary covert feather extent, followed by secondary feather length and the shape of the wing tip. Although often considered a plastic character strongly linked to flight style, the estimated ancestral wing morphology is found to be generally conservative among basal parts of most major avian lineages. The radiation of birds is characterized by successive diversification into largely distinct areas of morphospace. However, aquatic taxa show convergence in feathering despite differences in flight style, and songbirds move into a region of morphospace also occupied by basal taxa but at markedly different body sizes. These results have implications for the proposed inference of flight style in extinct taxa. © 2015 The Author(s).

  2. Fracture trends identified by ERTS-1 imagery in Utah and Nevada

    NASA Technical Reports Server (NTRS)

    Jensen, M. L. (Principal Investigator); Erickson, M. P.; Smith, M. R.

    1973-01-01

    The author has identified the following significant results. In the Utah-Nevada area, linear structural trends recorded on ERTS-1 imagery conform in part to previously recognized structures. In addition, the ERTS-1 imagery reveals cryptic structures not previously identified and not readily apparent in other imagery. These structures are illustrated by prominent east-west trending structures which appear to be concentrated in pre-volcanic rocks. This suggests that the structures are older than many of those with other trends which are equally prominent in volcanic and non-volcanic terrain. Since the older east-west structures may have controlled early Tertiary emplacement of magma or the ascent of mineralizing fluids, their recognition is important in minerial exploration. Soil-gas sampling and analysis for mercury content is being continued over structures, and projected trends of buried structures which appear, from studies of ERTS-1 imagery, to be favorable to mineralization. Comparison of ERTS-1 and Skylab imagery indicated that ERTS-1 imagery records more previously unrecognized linear structures than the Skylab imagery. In differentiating and identifying different rock types, the Skylab imagery appears to be more effective.

  3. GDH3 encodes a glutamate dehydrogenase isozyme, a previously unrecognized route for glutamate biosynthesis in Saccharomyces cerevisiae.

    PubMed Central

    Avendaño, A; Deluna, A; Olivera, H; Valenzuela, L; Gonzalez, A

    1997-01-01

    It has been considered that the yeast Saccharomyces cerevisiae, like many other microorganisms, synthesizes glutamate through the action of NADP+-glutamate dehydrogenase (NADP+-GDH), encoded by GDH1, or through the combined action of glutamine synthetase and glutamate synthase (GOGAT), encoded by GLN1 and GLT1, respectively. A double mutant of S. cerevisiae lacking NADP+-GDH and GOGAT activities was constructed. This strain was able to grow on ammonium as the sole nitrogen source and thus to synthesize glutamate through an alternative pathway. A computer search for similarities between the GDH1 nucleotide sequence and the complete yeast genome was carried out. In addition to identifying its cognate sequence at chromosome XIV, the search found that GDH1 showed high identity with a previously recognized open reading frame (GDH3) of chromosome I. Triple mutants impaired in GDH1, GLT1, and GDH3 were obtained. These were strict glutamate auxotrophs. Our results indicate that GDH3 plays a significant physiological role, providing glutamate when GDH1 and GLT1 are impaired. This is the first example of a microorganism possessing three pathways for glutamate biosynthesis. PMID:9287019

  4. HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.

    PubMed

    Scott, A A; Head, D R; Kopecky, K J; Appelbaum, F R; Theil, K S; Grever, M R; Chen, I M; Whittaker, M H; Griffith, B B; Licht, J D

    1994-07-01

    We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer (NK) cells. From a consecutive series of 350 cases of adult de novo acute myeloid leukemia (AML), we identified 20 cases (6%) with a unique immunophenotype: CD33+, CD56+, CD11a+, CD13lo, CD15lo, CD34+/-, HLA-DR-, CD16-. Multicolor flow cytometric assays confirmed the coexpression of myeloid (CD33, CD13, CD15) and NK cell-associated (CD56) antigens in each case, whereas reverse transcription polymerase chain reaction (RT-PCR) assays confirmed the identity of CD56 (neural cell adhesion molecule) in leukemic blasts. Although two cases expressed CD4, no case expressed CD2, CD3, or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor (TCR beta, gamma, delta). Leukemic blasts in the majority of cases shared unique morphologic features (deeply invaginated nuclear membranes, scant cytoplasm with fine azurophilic granularity, and finely granular Sudan black B and myeloperoxidase cytochemical reactivity) that were remarkably similar to those of acute promyelocytic leukemia (APL); particularly the microgranular variant (FAB AML-M3v). However, all 20 cases lacked the t(15;17) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha (RAR alpha) fusion transcript in RT-PCR assays; 12 cases had 46,XX or 46,XY karyotypes, whereas 2 cases had abnormalities of chromosome 17q: 1 with del(17)(q25) and the other with t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript. All cases tested (6/20), including the case with t(11;17), failed to differentiate in vitro in response to all-trans retinoic acid (ATRA), suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA. Four of 6 cases tested showed functional NK cell-mediated cytotoxicity, suggesting a relationship between these unique CD33+, CD56+, CD16- acute leukemias and

  5. A previously unrecognized role of C3a in proteinuric progressive nephropathy

    PubMed Central

    Morigi, Marina; Locatelli, Monica; Rota, Cinzia; Buelli, Simona; Corna, Daniela; Rizzo, Paola; Abbate, Mauro; Conti, Debora; Perico, Luca; Longaretti, Lorena; Benigni, Ariela; Zoja, Carlamaria; Remuzzi, Giuseppe

    2016-01-01

    Podocyte loss is the initial event in the development of glomerulosclerosis, the structural hallmark of progressive proteinuric nephropathies. Understanding mechanisms underlying glomerular injury is the key challenge for identifying novel therapeutic targets. In mice with protein-overload induced by bovine serum albumin (BSA), we evaluated whether the alternative pathway (AP) of complement mediated podocyte depletion and podocyte-dependent parietal epithelial cell (PEC) activation causing glomerulosclerosis. Factor H (Cfh−/−) or factor B-deficient mice were studied in comparison with wild-type (WT) littermates. WT+BSA mice showed podocyte depletion accompanied by glomerular complement C3 and C3a deposits, PEC migration to capillary tuft, proliferation, and glomerulosclerosis. These changes were more prominent in Cfh−/− +BSA mice. The pathogenic role of AP was documented by data that factor B deficiency preserved glomerular integrity. In protein-overload mice, PEC dysregulation was associated with upregulation of CXCR4 and GDNF/c-Ret axis. In vitro studies provided additional evidence of a direct action of C3a on proliferation and CXCR4-related migration of PECs. These effects were enhanced by podocyte-derived GDNF. In patients with proteinuric nephropathy, glomerular C3/C3a paralleled PEC activation, CXCR4 and GDNF upregulation. These results indicate that mechanistically uncontrolled AP complement activation is not dispensable for podocyte-dependent PEC activation resulting in glomerulosclerosis. PMID:27345360

  6. Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements.

    PubMed

    Andreasson, P; Johansson, B; Billström, R; Garwicz, S; Mitelman, F; Höglund, M

    1998-03-01

    Thirty-two hematologic malignancies--nine with cytogenetically identified 12p abnormalities and 23 with whole or partial losses of chromosome 12--were selected for fluorescence in situ hybridization (FISH) investigations of 12p. These analyses revealed structural 12p changes, such as translocations, deletions, insertions, inversions and amplification, in 20 cases. ETV6 rearrangements were detected in three acute leukemias. One acute undifferentiated leukemia had t(4;12)(q12;p13) as the sole anomaly. The second case, an acute myeloid leukemia (AML), displayed complex abnormalities involving, among others, chromosomes 9 and 12. The third case, also an AML, had an insertion of the distal part of ETV6 into chromosome arm 11q and into multiple ring chromosomes, which also contained chromosome 11 material, resulting in an amplification of a possible fusion gene. The fusion partners in these cases remain to be identified. Thirty-one additional breakpoints on 12p could be characterized in detail. The majority of these breaks were shown to result in interchromosomal rearrangements, possibly indicating the location of hitherto unrecognized genes of importance in the pathogenesis of hematologic malignancies. The FISH analyses disclosed terminal or interstitial 12p deletions in 18 cases. Seven myeloid malignancies showed deletions restricted to a region, including ETV6 and CDKN1B, which has been reported to be frequently lost in leukemias. In four cases, the deletions involved both these genes, whereas two AML displayed loss of CDKN1B but not ETV6, supporting previously reported findings indicating a region of deletion not including this gene. However, one myelodysplastic syndrome lacked one copy of ETV6 but not CDKN1B. Hence, we suggest a minimal region of deletion on 12p located between the ETV6 and CDKN1B genes.

  7. Prevalence of unrecognized diabetes, prediabetes and metabolic syndrome in patients undergoing elective percutaneous coronary intervention.

    PubMed

    Balakrishnan, Revathi; Berger, Jeffrey S; Tully, Lisa; Vani, Anish; Shah, Binita; Burdowski, Joseph; Fisher, Edward; Schwartzbard, Arthur; Sedlis, Steven; Weintraub, Howard; Underberg, James A; Danoff, Ann; Slater, James A; Gianos, Eugenia

    2015-09-01

    Diabetes mellitus (DM) and metabolic syndrome are important targets for secondary prevention in cardiovascular disease. However, the prevalence in patients undergoing elective percutaneous coronary intervention is not well defined. We aimed to analyse the prevalence and characteristics of patients undergoing percutaneous coronary intervention with previously unrecognized prediabetes, diabetes and metabolic syndrome. Data were collected from 740 patients undergoing elective percutaneous coronary intervention between November 2010 and March 2013 at a tertiary referral center. Prevalence of DM and prediabetes was evaluated using Haemoglobin A1c (A1c ≥ 6.5% for DM, A1c 5.7-6.4% for prediabetes). A modified definition was used for metabolic syndrome [three or more of the following criteria: body mass index ≥30 kg/m2; triglycerides ≥ 150 mg/dL; high density lipoprotein <40 mg/dL in men and <50 mg/dL in women; systolic blood pressure ≥ 130 mmHg and/or diastolic ≥ 85 mmHg; and A1c ≥ 5.7% or on therapy]. Mean age was 67 years, median body mass index was 28.2 kg/m(2) and 39% had known DM. Of those without known DM, 8.3% and 58.5% met A1c criteria for DM and for prediabetes at time of percutaneous coronary intervention. Overall, 54.9% met criteria for metabolic syndrome (69.2% of patients with DM and 45.8% of patients without DM). Among patients undergoing elective percutaneous coronary intervention, a substantial number were identified with a new DM, prediabetes, and/or metabolic syndrome. Routine screening for an abnormal glucometabolic state at the time of revascularization may be useful for identifying patients who may benefit from additional targeting of modifiable risk factors. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Community-acquired adult Escherichia coli meningitis leading to diagnosis of unrecognized retropharyngeal abscess and cervical spondylodiscitis: a case report.

    PubMed

    Kohlmann, Rebekka; Nefedev, Andrey; Kaase, Martin; Gatermann, Sören G

    2015-12-12

    Escherichia coli is a rare cause of community-acquired meningitis in adults unless predisposing factors are present (e.g., previous penetrating cranio-cerebral injury or neurosurgery, immunosuppression, chronic alcoholism, history of cancer, diabetes mellitus, advanced age). We describe the case of a 53-year-old woman, resident in Germany, suffering from community-acquired bacterial meningitis caused by CTX-M-9 type extended spectrum β-lactamase producing Escherichia coli. Because typical predisposing factors were not apparent, pathogen identification resulted in expanded diagnostics to exclude a distant or contiguous primary focus. By magnetic resonance tomography, a previously unrecognized large retropharyngeal abscess with cervical spondylodiscitis was detected. In retrospect, the patient had complained about neck pain for a few weeks prior to meningitis onset, but the symptoms were interpreted as being related to a herniated disk. Meningitis and osteomyelitis resolved completely under surgical treatment and meropenem therapy. In case of adult Escherichia coli meningitis, underlying diseases should always be carefully excluded, especially if predisposing factors are not apparent.

  9. Previously unrecognized behavioral phenotype in Gaucher disease type 3

    PubMed Central

    Potegal, Michael; Shapiro, Elsa G.; Nestrasil, Igor

    2017-01-01

    Objective: To provide a comprehensive description of abnormal behaviors in patients with Gaucher disease type 3 (GD3) and relate these behaviors to demographic, neurodevelopmental, and neurologic characteristics. Methods: Thirty-four Egyptian patients with GD3 (mean age of 7.9 years) were enrolled in the study. They were selected based on parent report and/or physician observation of one or more abnormal behaviors documented in 2 settings and by 2 different individuals and/or by video recording. Behaviors were grouped into 4 categories: Crying/Withdrawal, Impatience/Overactivity, Anger/Aggression, and Repetitive Acts. Baseline and follow-up 6–12 monthly neurologic evaluations included IQ assessment and an EEG. All patients were receiving enzyme replacement therapy (30–60 IU/kg every 2 weeks) and were followed for periods of 3–10 years. Results: Supranuclear palsy of horizontal gaze, and of both horizontal and vertical gaze, bulbar symptoms, seizures, convergent strabismus, abnormal gait, and neck retroflexion were present in 97.1%, 50%, 55.9%, 29.4%, 29.4%, 20.6%, and 4.4% of patients, respectively. The most abnormal behavioral features were excessive anger (88.2%) and aggression (64.7%), and both were significantly higher in males. Anger/Aggression scores were highly correlated with IQ but not with either EEG/Seizure status or neurologic signs. Conclusions: We describe behavioral problems with a unique pattern of excessive anger and aggression in patients with GD3. Defining these components using quantitative behavioral scoring methods holds promise to provide a marker of neurologic disease progression and severity. PMID:28634598

  10. RavN is a member of a previously unrecognized group of Legionella pneumophila E3 ubiquitin ligases

    PubMed Central

    Lin, Yi-Han; Evans, Timothy R.; Doms, Alexandra G.; Beauchene, Nicole A.; Hierro, Aitor

    2018-01-01

    The eukaryotic ubiquitylation machinery catalyzes the covalent attachment of the small protein modifier ubiquitin to cellular target proteins in order to alter their fate. Microbial pathogens exploit this post-translational modification process by encoding molecular mimics of E3 ubiquitin ligases, eukaryotic enzymes that catalyze the final step in the ubiquitylation cascade. Here, we show that the Legionella pneumophila effector protein RavN belongs to a growing class of bacterial proteins that mimic host cell E3 ligases to exploit the ubiquitylation pathway. The E3 ligase activity of RavN was located within its N-terminal region and was dependent upon interaction with a defined subset of E2 ubiquitin-conjugating enzymes. The crystal structure of the N-terminal region of RavN revealed a U-box-like motif that was only remotely similar to other U-box domains, indicating that RavN is an E3 ligase relic that has undergone significant evolutionary alteration. Substitution of residues within the predicted E2 binding interface rendered RavN inactive, indicating that, despite significant structural changes, the mode of E2 recognition has remained conserved. Using hidden Markov model-based secondary structure analyses, we identified and experimentally validated four additional L. pneumophila effectors that were not previously recognized to possess E3 ligase activity, including Lpg2452/SdcB, a new paralog of SidC. Our study provides strong evidence that L. pneumophila is dedicating a considerable fraction of its effector arsenal to the manipulation of the host ubiquitylation pathway. PMID:29415051

  11. Identification and characterization of unrecognized viruses in stool samples of non-polio acute flaccid paralysis children by simplified VIDISCA.

    PubMed

    Shaukat, Shahzad; Angez, Mehar; Alam, Muhammad Masroor; Jebbink, Maarten F; Deijs, Martin; Canuti, Marta; Sharif, Salmaan; de Vries, Michel; Khurshid, Adnan; Mahmood, Tariq; van der Hoek, Lia; Zaidi, Syed Sohail Zahoor

    2014-08-12

    The use of sequence independent methods combined with next generation sequencing for identification purposes in clinical samples appears promising and exciting results have been achieved to understand unexplained infections. One sequence independent method, Virus Discovery based on cDNA Amplified Fragment Length Polymorphism (VIDISCA) is capable of identifying viruses that would have remained unidentified in standard diagnostics or cell cultures. VIDISCA is normally combined with next generation sequencing, however, we set up a simplified VIDISCA which can be used in case next generation sequencing is not possible. Stool samples of 10 patients with unexplained acute flaccid paralysis showing cytopathic effect in rhabdomyosarcoma cells and/or mouse cells were used to test the efficiency of this method. To further characterize the viruses, VIDISCA-positive samples were amplified and sequenced with gene specific primers. Simplified VIDISCA detected seven viruses (70%) and the proportion of eukaryotic viral sequences from each sample ranged from 8.3 to 45.8%. Human enterovirus EV-B97, EV-B100, echovirus-9 and echovirus-21, human parechovirus type-3, human astrovirus probably a type-3/5 recombinant, and tetnovirus-1 were identified. Phylogenetic analysis based on the VP1 region demonstrated that the human enteroviruses are more divergent isolates circulating in the community. Our data support that a simplified VIDISCA protocol can efficiently identify unrecognized viruses grown in cell culture with low cost, limited time without need of advanced technical expertise. Also complex data interpretation is avoided thus the method can be used as a powerful diagnostic tool in limited resources. Redesigning the routine diagnostics might lead to additional detection of previously undiagnosed viruses in clinical samples of patients.

  12. Screening for autism identifies behavioral disorders in children functional defecation disorders.

    PubMed

    Kuizenga-Wessel, Sophie; Di Lorenzo, Carlo; Nicholson, Lisa M; Butter, Eric M; Ratliff-Schaub, Karen L; Benninga, Marc A; Williams, Kent C

    2016-10-01

    This study prospectively assessed whether positive screening surveys for autism spectrum disorders (ASDs) in children with functional defecation disorders (FDDs) accurately identify ASD. Parents of children (4-12 years) who met Rome III criteria for functional constipation (FC), FC with fecal incontinence (FI) and functional nonretentive FI (FNRFI) completed two ASD screening surveys. Children with positive screens were referred for psychological evaluation, and a year later, follow-up surveys were conducted. Of the 97 study participants, 30.9 % were diagnosed with FC, 62.9 % with FC with FI, and 6.2 % with FNRFI. ASD surveys were positive for 27 children (27.8 %). New DSM diagnoses were made in 10 out of the 15 children that completed further evaluation. Two (2.1 %) met criteria for ASD, and 12 (12.4 %) met criteria for other behavioral disorders. Average SRS and SCQ-L scores were higher in subjects with FC with FI as compared to FC alone and in those who reported no improvement versus those who reported improvement 1 year later. While positive ASD screening surveys did not correctly identify ASD in the majority, it did help to identify other unrecognized behavioral disorders in children with FDD. High screening scores were more common in children with FC with FI and in children with poorer responses to current medical treatments. •A prior study found that 29 % of children with FDD scored positive on ASD screening questionnaires. •Whether positive screens correctly identify ASD in children with FDD is unknown. What is New: •This study shows that positive ASD screens do not correctly identify ASD in children with FDD. However, the use of ASD screening questionnaires can identify previously unrecognized and untreated behavioral/developmental disorders in children with FDD. •High screening scores are more common in children with FC with FI and in children with poorer responses to current medical treatments.

  13. Unrecognized astrometric confusion in the Galactic Centre

    NASA Astrophysics Data System (ADS)

    Plewa, P. M.; Sari, R.

    2018-06-01

    The Galactic Centre is a crowded stellar field and frequent unrecognized events of source confusion, which involve undetected faint stars, are expected to introduce astrometric noise on a sub-mas level. This confusion noise is the main non-instrumental effect limiting the astrometric accuracy and precision of current near-infrared imaging observations and the long-term monitoring of individual stellar orbits in the vicinity of the central supermassive black hole. We self-consistently simulate the motions of the known and the yet unidentified stars to characterize this noise component and show that a likely consequence of source confusion is a bias in estimates of the stellar orbital elements, as well as the inferred mass and distance of the black hole, in particular if stars are being observed at small projected separations from it, such as the star S2 during pericentre passage. Furthermore, we investigate modelling the effect of source confusion as an additional noise component that is time-correlated, demonstrating a need for improved noise models to obtain trustworthy estimates of the parameters of interest (and their uncertainties) in future astrometric studies.

  14. Pulmonary hypertension in patients with congenital portosystemic venous shunt: a previously unrecognized association.

    PubMed

    Ohno, Takuro; Muneuchi, Jun; Ihara, Kenji; Yuge, Tetsuji; Kanaya, Yoshiaki; Yamaki, Shigeo; Hara, Toshiro

    2008-04-01

    Pulmonary arterial hypertension has been reported to be observed in association with acquired portal hypertension. However, the contribution of congenital anomalies occurring in the portal system to the development of pulmonary arterial hypertension remains to be elucidated. Nine patients with congenital portosystemic venous shunt were studied from January 1990 through September 2005. Patent ductus venosus was detected in 5 patients, including 3 patients with an absence of the portal vein. The presence of either a gastrorenal or splenorenal shunt was evident in another 4 patients. Six patients had a history of hypergalactosemia with normal enzyme activities, as seen during neonatal screening. Six (66.7%) of the 9 patients were identified to have clinically significant pulmonary arterial hypertension (mean pulmonary artery pressure: 34-79 mm Hg; pulmonary vascular resistances: 5.12-38.07 U). The median age at the onset of pulmonary arterial hypertension was 12 years and 3 months. Histologic studies of lung specimens, which were available in 4 of the 9 patients with congenital portosystemic venous shunt, showed small arterial microthrombotic lesions in 3 patients. This characteristic finding was recognized even in the congenital portosystemic venous shunt patients without PAH. This study demonstrated thromboembolic pulmonary arterial hypertension to be a crucial complication in congenital portosystemic venous shunt, and this pathologic state may be latently present in patients with pulmonary arterial hypertension of unknown etiology.

  15. Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke.

    PubMed

    Wozniak, Marcella A; Kittner, Steven J; Tuhrim, Stanley; Cole, John W; Stern, Barney; Dobbins, Mark; Grace, Marie E; Nazarenko, Irina; Dobrovolny, Robert; McDade, Eric; Desnick, Robert J

    2010-01-01

    The cause of initial ischemic stroke in up to 30% of young patients remains unclear. Fabry disease, due to deficient alpha-galactosidase A (alpha-Gal A) activity, is a vascular endothelial glycosphingolipid storage disease typically presenting in childhood. With advancing age, patients develop renal, cardiac, and cerebrovascular disease and die prematurely. A European study suggested an increased prevalence of unrecognized Fabry disease in patients with cryptogenic stroke. We hypothesized that alpha-Gal A deficiency is a rare cause of initial early-onset ischemic stroke in men. The Stroke Prevention in Young Men Study enrolled >550 men (15 to 49 years) with first ischemic stroke in the Baltimore-Washington area in 2004 to 2007. Frozen plasma samples were assayed for alpha-Gal A activity, and DNA from patients with consistently low plasma alpha-Gal A activities were sequenced. The study sample consisted of 558 men (42% African-American; median age 44 years). Stroke was cryptogenic in 154 men (40% African-American). In 10 patients with low plasma alpha-Gal A activities, DNA sequencing identified alterations in the alpha-Gal A gene in 2 patients. The polymorphism, D313Y, which results in low plasma enzyme activity, but near normal levels of cellular activity was seen in one European-American male. The Fabry disease-causing A143T mutation was seen in an African-American male with cryptogenic stroke (0.18% of all strokes: upper 95% CI=0.53%; 0.65% of cryptogenic strokes: upper 95% CI=1.92%). In this biracial population, unrecognized Fabry disease is a rare but treatable cause of initial ischemic stroke in young men.

  16. Nocturnal Wakefulness as a Previously Unrecognized Risk Factor for Suicide.

    PubMed

    Perlis, Michael L; Grandner, Michael A; Brown, Gregory K; Basner, Mathias; Chakravorty, Subhajit; Morales, Knashawn H; Gehrman, Philip R; Chaudhary, Ninad S; Thase, Michael E; Dinges, David F

    2016-06-01

    Suicide is a major public health problem and the 10th leading cause of death in the United States. The identification of modifiable risk factors is essential for reducing the prevalence of suicide. Recently, it has been shown that insomnia and nightmares significantly increase the risk for suicidal ideation, attempted suicide, and death by suicide. While both forms of sleep disturbance may independently confer risk, and potentially be modifiable risk factors, it is also possible that simply being awake at night represents a specific vulnerability for suicide. The present analysis evaluates the frequency of completed suicide per hour while taking into account the percentage of individuals awake at each hour. Archival analyses were conducted estimating the time of fatal injury using the National Violent Death Reporting System for 2003-2010 and the proportion of the American population awake per hour across the 24-hour day using the American Time Use Survey. The mean ± SD incident rate from 06:00-23:59 was 2.2% ± 0.7%, while the mean ± SD incident rate from 00:00-05:59 was 10.3% ± 4.9%. The maximum incident rate was from 02:00-02:59 (16.3%). Hour-by-hour observed values differed from those that would be expected by chance (P < .001), and when 6-hour blocks were examined, the observed frequency at night was 3.6 times higher than would be expected by chance (P < .001). Being awake at night confers greater risk for suicide than being awake at other times of the day, suggesting that disturbances of sleep or circadian neurobiology may potentiate suicide risk. © Copyright 2016 Physicians Postgraduate Press, Inc.

  17. Combinatorial phenotypic screen uncovers unrecognized family of extended thiourea inhibitors with copper-dependent anti-staphylococcal activity.

    PubMed

    Dalecki, Alex G; Malalasekera, Aruni P; Schaaf, Kaitlyn; Kutsch, Olaf; Bossmann, Stefan H; Wolschendorf, Frank

    2016-04-01

    The continuous rise of multi-drug resistant pathogenic bacteria has become a significant challenge for the health care system. In particular, novel drugs to treat infections of methicillin-resistant Staphylococcus aureus strains (MRSA) are needed, but traditional drug discovery campaigns have largely failed to deliver clinically suitable antibiotics. More than simply new drugs, new drug discovery approaches are needed to combat bacterial resistance. The recently described phenomenon of copper-dependent inhibitors has galvanized research exploring the use of metal-coordinating molecules to harness copper's natural antibacterial properties for therapeutic purposes. Here, we describe the results of the first concerted screening effort to identify copper-dependent inhibitors of Staphylococcus aureus. A standard library of 10 000 compounds was assayed for anti-staphylococcal activity, with hits defined as those compounds with a strict copper-dependent inhibitory activity. A total of 53 copper-dependent hit molecules were uncovered, similar to the copper independent hit rate of a traditionally executed campaign conducted in parallel on the same library. Most prominent was a hit family with an extended thiourea core structure, termed the NNSN motif. This motif resulted in copper-dependent and copper-specific S. aureus inhibition, while simultaneously being well tolerated by eukaryotic cells. Importantly, we could demonstrate that copper binding by the NNSN motif is highly unusual and likely responsible for the promising biological qualities of these compounds. A subsequent chemoinformatic meta-analysis of the ChEMBL chemical database confirmed the NNSNs as an unrecognized staphylococcal inhibitor, despite the family's presence in many chemical screening libraries. Thus, our copper-biased screen has proven able to discover inhibitors within previously screened libraries, offering a mechanism to reinvigorate exhausted molecular collections.

  18. Minimizing the influence of unconscious bias in evaluations: a practical guide.

    PubMed

    Goldyne, Adam J

    2007-01-01

    The forensic psychiatrist's efforts to strive for objectivity may be impaired by unrecognized unconscious biases. The author presents a framework for understanding such biases. He then offers a practical approach for individual forensic psychiatrists who want to identify and minimize the influence of previously unrecognized biases on their evaluations.

  19. Unrecognized "AIDS" in Monkeys, 1969-1980: Explanations and Implications.

    PubMed

    Hammett, Theodore M; Bronson, Roderick T

    2016-06-01

    AIDS was recognized in humans in 1981 and a simian form was described in the years 1983 to 1985. However, beginning in the late 1960s, outbreaks of opportunistic infections of AIDS were seen in monkeys in the United States. This apparent syndrome went unrecognized at the time. We have assembled those early cases in monkeys and offer reasons why they did not result in earlier recognition of simian or human AIDS, including weaknesses in understanding disease mechanisms, absence of evidence of human retroviruses, and a climate of opinion that devalued investigation of infectious disease and immunologic origins of disease. The "epistemological obstacle" explains important elements of this history in that misconceptions blocked understanding of the dependent relationship among viral infection, immunodeficiency, and opportunistic diseases. Had clearer understanding of the evidence from monkeys allowed human AIDS to be recognized earlier, life-saving prevention and treatment interventions might have been implemented sooner.

  20. Chronic sinusitis associated with the use of unrecognized bone substitute: a case report.

    PubMed

    Beklen, Arzu; Pihakari, Antti; Rautemaa, Riina; Hietanen, Jarkko; Ali, Ahmed; Konttinen, Yrjö T

    2008-05-01

    Bone grafts are used for bone augmentation to ensure optimal implant placement. However, this procedure may sometimes cause sinusitis. The case of a 44-year-old woman with the diagnosis of recurrent and chronic sinusitis of her right maxillary sinus with a history of dental implant surgery is presented. After several attempts with normal standard sinusitis therapy, unrecognized bone substitute was removed from the sinus cavity, which finally led to resolution of the sinusitis. This case reiterates the importance of a careful examination, consultation, and second opinion for the selection of optimal treatment.

  1. Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation.

    PubMed

    Odell, Anahi V; Tran, Fanny; Foderaro, Jenna E; Poupart, Séverine; Pathak, Ravi; Westwood, Nicholas J; Ward, Gary E

    2015-01-01

    Differentiation of the protozoan parasite Toxoplasma gondii into its latent bradyzoite stage is a key event in the parasite's life cycle. Compound 2 is an imidazopyridine that was previously shown to inhibit the parasite lytic cycle, in part through inhibition of parasite cGMP-dependent protein kinase. We show here that Compound 2 can also enhance parasite differentiation, and we use yeast three-hybrid analysis to identify TgBRADIN/GRA24 as a parasite protein that interacts directly or indirectly with the compound. Disruption of the TgBRADIN/GRA24 gene leads to enhanced differentiation of the parasite, and the TgBRADIN/GRA24 knockout parasites show decreased susceptibility to the differentiation-enhancing effects of Compound 2. This study represents the first use of yeast three-hybrid analysis to study small-molecule mechanism of action in any pathogenic microorganism, and it identifies a previously unrecognized inhibitor of differentiation in T. gondii. A better understanding of the proteins and mechanisms regulating T. gondii differentiation will enable new approaches to preventing the establishment of chronic infection in this important human pathogen.

  2. [Biometric method for the description of the head of an unrecognized corpse for the purpose of personality individualization and identification].

    PubMed

    Zviagin, V N; Galitskaia, O I; Negasheva, M A

    2012-01-01

    We have determined absolute dimensions of the head and the relationship between the dimensions of its selected parts. The study enrolled adult subjects (mostly of Russian ethnicity) at the age from 17 to 22 years (1108 men and 1153 women). We calculated the normal values for the estimation of real dimensional characteristics and the frequency of their occurrence in the population. The proposed approach makes it possible to reliably identify the dimensional features of human appearance in terms of the quantitative verbal description (categories 1-5) and to reveal its most characteristic features. The results of this biometric study of the heads of unrecognized corpses obtained by the specially developed technology may be used in operational and search investigations, in the procedure of corpse identification, and forensic medical personality identification of a missing subject.

  3. Unrecognized Ingestion of Toxoplasma gondii Oocysts Leads to Congenital Toxoplasmosis and Causes Epidemics in North America

    PubMed Central

    Boyer, Kenneth; Hill, Dolores; Mui, Ernest; Wroblewski, Kristen; Karrison, Theodore; Dubey, J. P.; Sautter, Mari; Noble, A. Gwendolyn; Withers, Shawn; Swisher, Charles; Heydemann, Peter; Hosten, Tiffany; Babiarz, Jane; Lee, Daniel

    2011-01-01

    (See the Editorial Commentary by Linn, on pages 1090–1.) Background. Congenital toxoplasmosis presents as severe, life-altering disease in North America. If mothers of infants with congenital toxoplasmosis could be identified by risks, it would provide strong support for educating pregnant women about risks, to eliminate this disease. Conversely, if not all risks are identifiable, undetectable risks are suggested. A new test detecting antibodies to sporozoites demonstrated that oocysts were the predominant source of Toxoplasma gondii infection in 4 North American epidemics and in mothers of children in the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS). This novel test offered the opportunity to determine whether risk factors or demographic characteristics could identify mothers infected with oocysts. Methods. Acutely infected mothers and their congenitally infected infants were evaluated, including in-person interviews concerning risks and evaluation of perinatal maternal serum samples. Results. Fifty-nine (78%) of 76 mothers of congenitally infected infants in NCCCTS had primary infection with oocysts. Only 49% of these mothers identified significant risk factors for sporozoite acquisition. Socioeconomic status, hometown size, maternal clinical presentations, and ethnicity were not reliable predictors. Conclusions. Undetected contamination of food and water by oocysts frequently causes human infections in North America. Risks are often unrecognized by those infected. Demographic characteristics did not identify oocyst infections. Thus, although education programs describing hygienic measures may be beneficial, they will not suffice to prevent the suffering and economic consequences associated with congenital toxoplasmosis. Only a vaccine or implementation of systematic serologic testing of pregnant women and newborns, followed by treatment, will prevent most congenital toxoplasmosis in North America. PMID:22021924

  4. Previously unrecognized stages of species-specific colonization in the mutualism between Xenorhabdus bacteria and Steinernema nematodes

    PubMed Central

    Chaston, John M.; Murfin, Kristen E.; Heath-Heckman, Elizabeth A.; Goodrich-Blair, Heidi

    2013-01-01

    Summary The specificity of a horizontally transmitted microbial symbiosis is often defined by molecular communication between host and microbe during initial engagement, which can occur in discrete stages. In the symbiosis between Steinernema nematodes and Xenorhabdus bacteria, previous investigations focused on bacterial colonization of the intestinal lumen (receptacle) of the nematode infective juvenile (IJ), as this was the only known persistent, intimate, and species-specific contact between the two. Here we show that bacteria colonize the anterior intestinal cells of other nematode developmental stages in a species-specific manner. Also, we describe three processes that only occur in juveniles that are destined to become IJs. First, a few bacterial cells colonize the nematode pharyngeal-intestinal valve (PIV) anterior to the intestinal epithelium. Second, the nematode intestine constricts while bacteria initially remain in the PIV. Third, anterior intestinal constriction relaxes and colonizing bacteria occupy the receptacle. At each stage, colonization requires X. nematophila symbiosis region 1 (SR1) genes and is species-specific: X. szentirmaii, which naturally lacks SR1, does not colonize unless SR1 is ectopically expressed. These findings reveal new aspects of Xenorhabdus bacteria interactions with and transmission by their Steinernema nematode hosts, and demonstrate that bacterial SR1 genes aid in colonizing nematode epithelial surfaces. PMID:23480552

  5. NCI Helps Children’s Hospital of Philadelphia to Identify and Treat New Target in Pediatric Cancer | Poster

    Cancer.gov

    There may be a new, more effective method for treating high-risk neuroblastoma, according to scientists at the Children’s Hospital of Philadelphia and collaborators in the Cancer and Inflammation Program at NCI at Frederick. Together, the groups published a study describing a previously unrecognized protein on neuroblastoma cells, called GPC2, as well as the creation of a

  6. Erythrocyte shape abnormalities, membrane oxidative damage, and β-actin alterations: an unrecognized triad in classical autism.

    PubMed

    Ciccoli, Lucia; De Felice, Claudio; Paccagnini, Eugenio; Leoncini, Silvia; Pecorelli, Alessandra; Signorini, Cinzia; Belmonte, Giuseppe; Guerranti, Roberto; Cortelazzo, Alessio; Gentile, Mariangela; Zollo, Gloria; Durand, Thierry; Valacchi, Giuseppe; Rossi, Marcello; Hayek, Joussef

    2013-01-01

    Autism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily rising in frequency and treatment refractory, where the search for biological markers is of paramount importance. Although red blood cells (RBCs) membrane lipidomics and rheological variables have been reported to be altered, with some suggestions indicating an increased lipid peroxidation in the erythrocyte membrane, to date no information exists on how the oxidative membrane damage may affect cytoskeletal membrane proteins and, ultimately, RBCs shape in autism. Here, we investigated RBC morphology by scanning electron microscopy in patients with classical autism, that is, the predominant ASDs phenotype (age range: 6-26 years), nonautistic neurodevelopmental disorders (i.e., "positive controls"), and healthy controls (i.e., "negative controls"). A high percentage of altered RBCs shapes, predominantly elliptocytes, was observed in autistic patients, but not in both control groups. The RBCs altered morphology in autistic subjects was related to increased erythrocyte membrane F2-isoprostanes and 4-hydroxynonenal protein adducts. In addition, an oxidative damage of the erythrocyte membrane β-actin protein was evidenced. Therefore, the combination of erythrocyte shape abnormalities, erythrocyte membrane oxidative damage, and β-actin alterations constitutes a previously unrecognized triad in classical autism and provides new biological markers in the diagnostic workup of ASDs.

  7. Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical Autism

    PubMed Central

    Ciccoli, Lucia; De Felice, Claudio; Pecorelli, Alessandra; Belmonte, Giuseppe; Guerranti, Roberto; Cortelazzo, Alessio; Durand, Thierry; Valacchi, Giuseppe; Rossi, Marcello; Hayek, Joussef

    2013-01-01

    Autism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily rising in frequency and treatment refractory, where the search for biological markers is of paramount importance. Although red blood cells (RBCs) membrane lipidomics and rheological variables have been reported to be altered, with some suggestions indicating an increased lipid peroxidation in the erythrocyte membrane, to date no information exists on how the oxidative membrane damage may affect cytoskeletal membrane proteins and, ultimately, RBCs shape in autism. Here, we investigated RBC morphology by scanning electron microscopy in patients with classical autism, that is, the predominant ASDs phenotype (age range: 6–26 years), nonautistic neurodevelopmental disorders (i.e., “positive controls”), and healthy controls (i.e., “negative controls”). A high percentage of altered RBCs shapes, predominantly elliptocytes, was observed in autistic patients, but not in both control groups. The RBCs altered morphology in autistic subjects was related to increased erythrocyte membrane F2-isoprostanes and 4-hydroxynonenal protein adducts. In addition, an oxidative damage of the erythrocyte membrane β-actin protein was evidenced. Therefore, the combination of erythrocyte shape abnormalities, erythrocyte membrane oxidative damage, and β-actin alterations constitutes a previously unrecognized triad in classical autism and provides new biological markers in the diagnostic workup of ASDs. PMID:24453417

  8. Nitrotoga-like bacteria are previously unrecognized key nitrite oxidizers in full-scale wastewater treatment plants.

    PubMed

    Lücker, Sebastian; Schwarz, Jasmin; Gruber-Dorninger, Christiane; Spieck, Eva; Wagner, Michael; Daims, Holger

    2015-03-01

    Numerous past studies have shown members of the genus Nitrospira to be the predominant nitrite-oxidizing bacteria (NOB) in nitrifying wastewater treatment plants (WWTPs). Only recently, the novel NOB 'Candidatus Nitrotoga arctica' was identified in permafrost soil and a close relative was enriched from activated sludge. Still, little is known about diversity, distribution and functional importance of Nitrotoga in natural and engineered ecosystems. Here we developed Nitrotoga 16S rRNA-specific PCR primers and fluorescence in situ hybridization (FISH) probes, which were applied to screen activated sludge samples from 20 full-scale WWTPs. Nitrotoga-like bacteria were detected by PCR in 11 samples and reached abundances detectable by FISH in seven sludges. They coexisted with Nitrospira in most of these WWTPs, but constituted the only detectable NOB in two systems. Quantitative FISH revealed that Nitrotoga accounted for nearly 2% of the total bacterial community in one of these plants, a number comparable to Nitrospira abundances in other WWTPs. Spatial statistics revealed that Nitrotoga coaggregated with ammonia-oxidizing bacteria, strongly supporting a functional role in nitrite oxidation. This activity was confirmed by FISH in combination with microradiography, which revealed nitrite-dependent autotrophic carbon fixation by Nitrotoga in situ. Correlation of the presence or absence with WWTP operational parameters indicated low temperatures as a main factor supporting high Nitrotoga abundances, although in incubation experiments these NOB remained active over an unexpected range of temperatures, and also at different ambient nitrite concentrations. In conclusion, this study demonstrates that Nitrotoga can be functionally important nitrite oxidizers in WWTPs and can even represent the only known NOB in engineered systems.

  9. In silico molecular comparisons of C. elegans and mammalian pharmacology identify distinct targets that regulate feeding.

    PubMed

    Lemieux, George A; Keiser, Michael J; Sassano, Maria F; Laggner, Christian; Mayer, Fahima; Bainton, Roland J; Werb, Zena; Roth, Bryan L; Shoichet, Brian K; Ashrafi, Kaveh

    2013-11-01

    Phenotypic screens can identify molecules that are at once penetrant and active on the integrated circuitry of a whole cell or organism. These advantages are offset by the need to identify the targets underlying the phenotypes. Additionally, logistical considerations limit screening for certain physiological and behavioral phenotypes to organisms such as zebrafish and C. elegans. This further raises the challenge of elucidating whether compound-target relationships found in model organisms are preserved in humans. To address these challenges we searched for compounds that affect feeding behavior in C. elegans and sought to identify their molecular mechanisms of action. Here, we applied predictive chemoinformatics to small molecules previously identified in a C. elegans phenotypic screen likely to be enriched for feeding regulatory compounds. Based on the predictions, 16 of these compounds were tested in vitro against 20 mammalian targets. Of these, nine were active, with affinities ranging from 9 nM to 10 µM. Four of these nine compounds were found to alter feeding. We then verified the in vitro findings in vivo through genetic knockdowns, the use of previously characterized compounds with high affinity for the four targets, and chemical genetic epistasis, which is the effect of combined chemical and genetic perturbations on a phenotype relative to that of each perturbation in isolation. Our findings reveal four previously unrecognized pathways that regulate feeding in C. elegans with strong parallels in mammals. Together, our study addresses three inherent challenges in phenotypic screening: the identification of the molecular targets from a phenotypic screen, the confirmation of the in vivo relevance of these targets, and the evolutionary conservation and relevance of these targets to their human orthologs.

  10. High-Throughput Screening To Identify Potent and Specific Inhibitors of Microbial Sulfate Reduction.

    PubMed

    Carlson, Hans K; Mullan, Mark R; Mosqueda, Lorraine A; Chen, Steven; Arkin, Michelle R; Coates, John D

    2017-06-20

    The selective perturbation of complex microbial ecosystems to predictably influence outcomes in engineered and industrial environments remains a grand challenge for geomicrobiology. In some industrial ecosystems, such as oil reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which is toxic, explosive, and corrosive. Despite the economic cost of sulfidogenesis, there has been minimal exploration of the chemical space of possible inhibitory compounds, and very little work has quantitatively assessed the selectivity of putative souring treatments. We have developed a high-throughput screening strategy to identify potent and selective inhibitors of SRM, quantitatively ranked the selectivity and potency of hundreds of compounds and identified previously unrecognized SRM selective inhibitors and synergistic interactions between inhibitors. Zinc pyrithione is the most potent inhibitor of sulfidogenesis that we identified, and is several orders of magnitude more potent than commonly used industrial biocides. Both zinc and copper pyrithione are also moderately selective against SRM. The high-throughput (HT) approach we present can be readily adapted to target SRM in diverse environments and similar strategies could be used to quantify the potency and selectivity of inhibitors of a variety of microbial metabolisms. Our findings and approach are relevant to efforts to engineer environmental ecosystems and also to understand the role of natural gradients in shaping microbial niche space.

  11. Unrecognized “AIDS” in Monkeys, 1969–1980: Explanations and Implications

    PubMed Central

    Bronson, Roderick T.

    2016-01-01

    AIDS was recognized in humans in 1981 and a simian form was described in the years 1983 to 1985. However, beginning in the late 1960s, outbreaks of opportunistic infections of AIDS were seen in monkeys in the United States. This apparent syndrome went unrecognized at the time. We have assembled those early cases in monkeys and offer reasons why they did not result in earlier recognition of simian or human AIDS, including weaknesses in understanding disease mechanisms, absence of evidence of human retroviruses, and a climate of opinion that devalued investigation of infectious disease and immunologic origins of disease. The “epistemological obstacle” explains important elements of this history in that misconceptions blocked understanding of the dependent relationship among viral infection, immunodeficiency, and opportunistic diseases. Had clearer understanding of the evidence from monkeys allowed human AIDS to be recognized earlier, life-saving prevention and treatment interventions might have been implemented sooner. PMID:27077355

  12. A Republican Egalitarian Approach to Bioethics: The Case of the Unrecognized Bedouin Villages in Israel.

    PubMed

    Filc, Dani; Davidovich, Nadav; Gottlieb, Nora

    2016-10-01

    This article argues that current, mainstream, liberal approaches to the right to health and to bioethics are not adequately aware of the structural and political character of health and illness. We propose a radical egalitarian definition of the right to health as the basis for the discussion of a republican egalitarian perspective on bioethics that redefines autonomy and stresses the importance of equality, political participation, and the common good. The violations of the right to health in unrecognized Bedouin villages in Israel are analyzed to exemplify the possibilities opened by the republican egalitarian approach. © The Author(s) 2015.

  13. Adenomyoepithelioma of the breast with associated atypical lobular hyperplasia: a previously unrecognized association with management implications.

    PubMed

    Zhang, Shuang; Huo, Lei; Arribas, Elsa; Middleton, Lavinia P

    2015-02-01

    Adenomyoepitheliomas of breast are rare tumors. We report for the first time a case of an adenomyoepithelioma of the breast with associated lobular neoplasia. A 53-year-old woman had an annual screening mammogram, which identified areas of asymmetry in her left breast at 4-5-o'clock position. Resection of the masses revealed a well-circumscribed, gray-white, firm discrete nodule (0.8 × 0.4 × 0.3 cm). The tumor was composed of both adenomyoepithelial cell hyperplasia and focal atypical lobular hyperplasia. The 2 cell populations had some overlapping histologic features. Immunohistochemical analysis demonstrated a biphasic proliferation with approximately equal parts of luminal epithelial cells with clear and rounded appearance and myoepithelial cells. The myoepithelial component of the proliferation expressed myosin, p63, CK5/6, S-100, and dimly expressed E-cadherin. The epithelial component of the proliferation strongly expressed E-cadherin. In the areas of atypical lobular hyperplasia, there was distinct loss E-cadherin expression. Awareness of this association is highly important to provide these patients adequate follow-up and treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Metal exposures from aluminum cookware: An unrecognized public health risk in developing countries.

    PubMed

    Weidenhamer, Jeffrey D; Fitzpatrick, Meghann P; Biro, Alison M; Kobunski, Peter A; Hudson, Michael R; Corbin, Rebecca W; Gottesfeld, Perry

    2017-02-01

    Removing lead from gasoline has resulted in decreases in blood lead levels in most of the world, but blood lead levels remain elevated in low and middle-income countries compared to more developed countries. Several reasons for this difference have been investigated, but few studies have examined the potential contribution from locally-made aluminum cookware. In a previous study of cookware from a single African country, Cameroon, artisanal aluminum cookware that is made from scrap metal released significant quantities of lead. In this study, 42 intact aluminum cookware items from ten developing countries were tested for their potential to release lead and other metals during cooking. Fifteen items released ≥1 microgram of lead per serving (250mL) when tested by boiling with dilute acetic acid for 2h. One pot, from Viet Nam, released 33, 1126 and 1426 micrograms per serving in successive tests. Ten samples released >1 microgram of cadmium per serving, and fifteen items released >1 microgram of arsenic per serving. The mean exposure estimate for aluminum was 125mg per serving, more than six times the World Health Organization's Provisional Tolerable Weekly Intake of 20mg/day for a 70kg adult, and 40 of 42 items tested exceeded this level. We conducted preliminary assessments of three potential methods to reduce metal leaching from this cookware. Coating the cookware reduced aluminum exposure per serving by >98%, and similar reductions were seen for other metals as well. Potential exposure to metals by corrosion during cooking may pose a significant and largely unrecognized public health risk which deserves urgent attention. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. The Impact of Repeated Health Checks for Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Felce, David; Baxter, Helen; Lowe, Kathy; Dunstan, Frank; Houston, Helen; Jones, Glyn; Felce, Janet; Kerr, Michael

    2008-01-01

    Background: An earlier study (Baxter "et al." 2006) found that a structured health check conducted in primary care identified clinically significant previously unrecognized morbidity among adults with intellectual disabilities. The aim here was to examine whether follow-up health checks would identify equally significant newly identified morbidity…

  16. Preeclampsia: is it because of the asymptomatic, unrecognized renal scars caused by urinary tract infections in childhood that become symptomatic with pregnancy?

    PubMed

    Ozlü, Tülay; Alçelik, Aytekin; Calişkan, Billur; Dönmez, Melahat Emine

    2012-11-01

    Preeclampsia is an important disease of pregnancy whose exact etiology is still unknown despite continuing developments in medicine. Although most commonly it is believed to be caused by a defective placentation, in this paper, we hypothesize that the primary underlying problem in the development of preeclampsia can be in kidneys in a greater proportion of cases than it is believed today. The increased intravascular volume and the increased work load of kidneys together with the resulting glomerular hypertrophy may precipitate nephrotic syndrome, which in this case is called "preeclampsia" in a previously affected kidney. Urinary tract infections in childhood leaving silent, unrecognized small scars in the kidneys may be the underlying renal cause which disrupts its silence with an increased work load of kidneys prominently occurring after the midtrimester. The histopathologic finding in kidneys with renal scars after childhood urinary tract infections and in preeclampsia is focal segmental glomerulosclerosis in the majority of cases and this similarity strengthens our hypothesis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Genetic structure of pike (Esox lucius) reveals a complex and previously unrecognized colonization history of Ireland

    PubMed Central

    Pedreschi, Debbi; Kelly-Quinn, Mary; Caffrey, Joe; O’Grady, Martin; Mariani, Stefano; Phillimore, Albert

    2014-01-01

    Aim We investigated genetic variation of Irish pike populations and their relationship with European outgroups, in order to elucidate the origin of this species to the island, which is largely assumed to have occurred as a human-mediated introduction over the past few hundred years. We aimed thereby to provide new insights into population structure to improve fisheries and biodiversity management in Irish freshwaters. Location Ireland, Britain and continental Europe. Methods A total of 752 pike (Esox lucius) were sampled from 15 locations around Ireland, and 9 continental European sites, and genotyped at six polymorphic microsatellite loci. Patterns and mechanisms of population genetic structure were assessed through a diverse array of methods, including Bayesian clustering, hierarchical analysis of molecular variance, and approximate Bayesian computation. Results Varying levels of genetic diversity and a high degree of population genetic differentiation were detected. Clear substructure within Ireland was identified, with two main groups being evident. One of the Irish populations showed high similarity with British populations. The other, more widespread, Irish strain did not group with any European population examined. Approximate Bayesian computation suggested that this widespread Irish strain is older, and may have colonized Ireland independently of humans. Main conclusions Population genetic substructure in Irish pike is high and comparable to the levels observed elsewhere in Europe. A comparison of evolutionary scenarios upholds the possibility that pike may have colonized Ireland in two ‘waves’, the first of which, being independent of human colonization, would represent the first evidence for natural colonization of a non-anadromous freshwater fish to the island of Ireland. Although further investigations using comprehensive genomic techniques will be necessary to confirm this, the present results warrant a reappraisal of current management strategies

  18. Genetic structure of pike (Esox lucius) reveals a complex and previously unrecognized colonization history of Ireland.

    PubMed

    Pedreschi, Debbi; Kelly-Quinn, Mary; Caffrey, Joe; O'Grady, Martin; Mariani, Stefano; Phillimore, Albert

    2014-03-01

    We investigated genetic variation of Irish pike populations and their relationship with European outgroups, in order to elucidate the origin of this species to the island, which is largely assumed to have occurred as a human-mediated introduction over the past few hundred years. We aimed thereby to provide new insights into population structure to improve fisheries and biodiversity management in Irish freshwaters. Ireland, Britain and continental Europe. A total of 752 pike ( Esox lucius ) were sampled from 15 locations around Ireland, and 9 continental European sites, and genotyped at six polymorphic microsatellite loci. Patterns and mechanisms of population genetic structure were assessed through a diverse array of methods, including Bayesian clustering, hierarchical analysis of molecular variance, and approximate Bayesian computation. Varying levels of genetic diversity and a high degree of population genetic differentiation were detected. Clear substructure within Ireland was identified, with two main groups being evident. One of the Irish populations showed high similarity with British populations. The other, more widespread, Irish strain did not group with any European population examined. Approximate Bayesian computation suggested that this widespread Irish strain is older, and may have colonized Ireland independently of humans. Population genetic substructure in Irish pike is high and comparable to the levels observed elsewhere in Europe. A comparison of evolutionary scenarios upholds the possibility that pike may have colonized Ireland in two 'waves', the first of which, being independent of human colonization, would represent the first evidence for natural colonization of a non-anadromous freshwater fish to the island of Ireland. Although further investigations using comprehensive genomic techniques will be necessary to confirm this, the present results warrant a reappraisal of current management strategies for this species.

  19. Novel application of the published kinase inhibitor set to identify therapeutic targets and pathways in triple negative breast cancer subtypes

    PubMed Central

    Phamduy, Theresa B.; Chrisey, Douglas B.

    2017-01-01

    Triple negative breast cancers (TNBCs) have high recurrence and metastasis rates. Acquisition of a mesenchymal morphology and phenotype in addition to driving migration is a consequential process that promotes metastasis. Although some kinases are known to regulate a mesenchymal phenotype, the role for a substantial portion of the human kinome remains uncharacterized. Here we evaluated the Published Kinase Inhibitor Set (PKIS) and screened a panel of TNBC cell lines to evaluate the compounds’ effects on a mesenchymal phenotype. Our screen identified 36 hits representative of twelve kinase inhibitor chemotypes based on reversal of the mesenchymal cell morphology, which was then prioritized to twelve compounds based on gene expression and migratory behavior analyses. We selected the most active compound and confirmed mesenchymal reversal on transcript and protein levels with qRT-PCR and Western Blot. Finally, we utilized a kinase array to identify candidate kinases responsible for the EMT reversal. This investigation shows the novel application to identify previously unrecognized kinase pathways and targets in acquisition of a mesenchymal TNBC phenotype that warrant further investigation. Future studies will examine specific roles of the kinases in mechanisms responsible for acquisition of the mesenchymal and/or migratory phenotype. PMID:28771473

  20. Development of a Simple Tool for Identifying Alcohol Use Disorder in Female Korean Drinkers from Previous Questionnaires.

    PubMed

    Seo, Yu Ri; Kim, Jong Sung; Kim, Sung Soo; Yoon, Seok Joon; Suh, Won Yoon; Youn, Kwangmi

    2016-01-01

    This study aimed to develop a simple tool for identifying alcohol use disorders in female Korean drinkers from previous questionnaires. This research was conducted on 400 women who consumed at least one alcoholic drink during the past month and visited the health promotion center at Chungnam National University Hospital between June 2013 to May 2014. Drinking habits and alcohol use disorders were assessed by structured interviews using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnostic criteria. The subjects were also asked to answer the Alcohol Use Disorders Identification Test (AUDIT), AUDIT-Consumption, CAGE (Cut down, Annoyed, Guilty, Eye-opener), TWEAK (Tolerance, Worried, Eye-opener, Amnesia, Kut down), TACE (Tolerance, Annoyed, Cut down, Eye-opener), and NET (Normal drinker, Eye-opener, Tolerance) questionnaires. The area under receiver operating characteristic (AUROC) of each question of the questionnaires on alcohol use disorders was assessed. After combining two questions with the largest AUROC, it was compared to other previous questionnaires. Among the 400 subjects, 58 (14.5%) were identified as having an alcohol use disorder. Two questions with the largest AUROC were question no. 7 in AUDIT, "How often during the last year have you had a feeling of guilt or remorse after drinking?" and question no. 5 in AUDIT, "How often during the past year have you failed to do what was normally expected from you because of drinking?" with an AUROC (95% confidence interval [CI]) of 0.886 (0.850-0.915) and 0.862 (0.824-0.894), respectively. The AUROC (95% CI) of the combination of the two questions was 0.958 (0.934-0.976) with no significant difference as compared to the existing AUDIT with the largest AUROC. The above results suggest that the simple tool consisting of questions no. 5 and no. 7 in AUDIT is useful in identifying alcohol use disorders in Korean female drinkers.

  1. Familial testicular germ cell tumor: no associated syndromic pattern identified

    PubMed Central

    2014-01-01

    Background Testicular germ cell tumor (TGCT) is the most common malignancy in young men. Familial clustering, epidemiologic evidence of increased risk with family or personal history, and the association of TGCT with genitourinary (GU) tract anomalies have suggested an underlying genetic predisposition. Linkage data have not identified a rare, highly-penetrant, single gene in familial TGCT (FTGCT) cases. Based on its association with congenital GU tract anomalies and suggestions that there is an intrauterine origin to TGCT, we hypothesized the existence of unrecognized dysmorphic features in FTGCT. Methods We evaluated 38 FTGCT individuals and 41 first-degree relatives from 22 multiple-case families with detailed dysmorphology examinations, physician-based medical history and physical examination, laboratory testing, and genitourinary imaging studies. Results The prevalence of major abnormalities and minor variants did not significantly differ between either FTGCT individuals or their first-degree relatives when compared with normal population controls, except for tall stature, macrocephaly, flat midface, and retro-/micrognathia. However, these four traits were not manifest as a constellation of features in any one individual or family. We did detect an excess prevalence of the genitourinary anomalies cryptorchidism and congenital inguinal hernia in our population, as previously described in sporadic TGCT, but no congenital renal, retroperitoneal or mediastinal anomalies were detected. Conclusions Overall, our study did not identify a constellation of dysmorphic features in FTGCT individuals, which is consistent with results of genetic studies suggesting that multiple low-penetrance genes are likely responsible for FTGCT susceptibility. PMID:24559313

  2. Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice.

    PubMed

    Boosalis, Michael S; Sangerman, Jose I; White, Gary L; Wolf, Roman F; Shen, Ling; Dai, Yan; White, Emily; Makala, Levi H; Li, Biaoru; Pace, Betty S; Nouraie, Mehdi; Faller, Douglas V; Perrine, Susan P

    2015-01-01

    High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.

  3. Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice

    PubMed Central

    Boosalis, Michael S.; Sangerman, Jose I.; White, Gary L.; Wolf, Roman F.; Shen, Ling; Dai, Yan; White, Emily; Makala, Levi H.; Li, Biaoru; Pace, Betty S.; Nouraie, Mehdi; Faller, Douglas V.; Perrine, Susan P.

    2015-01-01

    High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies. PMID:26713848

  4. Intestinal Perforation Following Ileoscopy Through a Prolapsed Stoma in an Pediatric Intestinal Transplant Recipient With an Unrecognized Parastomal Hernia

    PubMed Central

    Yeh, Joanna; Hall, Theodore R.; Agopian, Vatche G.; Farmer, Douglas G.; Marcus, Elizabeth A.; Venick, Robert S.; Wozniak, Laura J.

    2016-01-01

    Ileoscopy with mucosal biopsy is fundamental in the management and surveillance of inflammatory bowel disease patients and intestinal transplant recipients. There is a paucity of data describing the risks of ileoscopy in the presence of a prolapsed stoma. Parastomal hernias are frequently associated with prolapsed stomas. We report the first case of perforation during ileoscopy in the setting of a prolapsed stoma and unrecognized parastomal hernia. Recognition of parastomal hernia associated with stoma prolapse is of paramount importance in patients undergoing ileoscopy as it may increase the risk of perforation. PMID:27807575

  5. NCI Helps Children’s Hospital of Philadelphia to Identify and Treat New Target in Pediatric Cancer | Poster

    Cancer.gov

    There may be a new, more effective method for treating high-risk neuroblastoma, according to scientists at the Children’s Hospital of Philadelphia and collaborators in the Cancer and Inflammation Program at NCI at Frederick. Together, the groups published a study describing a previously unrecognized protein on neuroblastoma cells, called GPC2, as well as the creation of a novel antibody-drug conjugate, a combination of a human antibody and a naturally occurring anticancer drug, that locates and binds to GPC2 in a highly efficient way.

  6. Previously unrecognized regional structure of the Coastal Belt of the Franciscan Complex, northern California, revealed by magnetic data

    USGS Publications Warehouse

    Langenheim, Victoria; Jachens, Robert C.; Wentworth, Carl M.; McLaughlin, Robert J.

    2013-01-01

    Magnetic anomalies provide surprising structural detail within the previously undivided Coastal Belt, the westernmost, youngest, and least-metamorphosed part of the Franciscan Complex of northern California. Although the Coastal Belt consists almost entirely of arkosic graywacke and shale of mainly Eocene age, new detailed aeromagnetic data show that it is pervasively marked by long, narrow, and regularly spaced anomalies. These anomalies arise from relatively simple tabular bodies composed principally of magnetic basalt or graywacke confi ned mainly to the top couple of kilometers, even though metamorphic grade indicates that these rocks have been more deeply buried, at depths of 5–8 km. If true, this implies surprisingly uniform uplift of these rocks. The basalt (and associated Cretaceous limestone) occurs largely in the northern part of the Coastal Belt; the graywacke is recognized only in the southern Coastal Belt and is magnetic because it contains andesitic grains. The magnetic grains were not derived from the basalt, and thus require a separate source. The anomalies defi ne simple patterns that can be related to folding and faulting within the Coastal Belt. This apparent simplicity belies complex structure mapped at outcrop scale, which can be explained if the relatively simple tabular bodies are internally deformed, fault-bounded slabs. One mechanism that can explain the widespread lateral extent of the thin layers of basalt is peeling up of the uppermost part of the oceanic crust into the accretionary prism, controlled by porosity and permeability contrasts caused by alteration in the upper part of the subducting slab. It is not clear, however, how this mechanism might generate fault-bounded layers containing magnetic graywacke. We propose that structural domains defined by anomaly trend, wavelength, and source reflect imbrication and folding during the accretion process and local plate interactions as the Mendocino triple junction migrated north, a

  7. Previously unrecognized regional structure of the Coastal Belt of the Franciscan Complex, northern California, revealed by magnetic data

    USGS Publications Warehouse

    Langenheim, V.E.; Jachens, R.C.; Wentworth, C.M.; McLaughlin, R.J.

    2013-01-01

    Magnetic anomalies provide surprising structural detail within the previously undivided Coastal Belt, the westernmost, youngest, and least-metamorphosed part of the Franciscan Complex of northern California. Although the Coastal Belt consists almost entirely of arkosic graywacke and shale of mainly Eocene age, new detailed aeromagnetic data show that it is pervasively marked by long, narrow, and regularly spaced anomalies. These anomalies arise from relatively simple tabular bodies composed principally of magnetic basalt or graywacke confined mainly to the top couple of kilometers, even though metamorphic grade indicates that these rocks have been more deeply buried, at depths of 5–8 km. If true, this implies surprisingly uniform uplift of these rocks. The basalt (and associated Cretaceous limestone) occurs largely in the northern part of the Coastal Belt; the graywacke is recognized only in the southern Coastal Belt and is magnetic because it contains andesitic grains. The magnetic grains were not derived from the basalt, and thus require a separate source. The anomalies define simple patterns that can be related to folding and faulting within the Coastal Belt. This apparent simplicity belies complex structure mapped at outcrop scale, which can be explained if the relatively simple tabular bodies are internally deformed, fault-bounded slabs. One mechanism that can explain the widespread lateral extent of the thin layers of basalt is peeling up of the uppermost part of the oceanic crust into the accretionary prism, controlled by porosity and permeability contrasts caused by alteration in the upper part of the subducting slab. It is not clear, however, how this mechanism might generate fault-bounded layers containing magnetic graywacke. We propose that structural domains defined by anomaly trend, wavelength, and source reflect imbrication and folding during the accretion process and local plate interactions as the Mendocino triple junction migrated north, a

  8. Diabetic eye disease among adults in Fiji with previously undiagnosed diabetes.

    PubMed

    Brian, Garry; Sikivou, Biu; Fischer-Harder, Konstanze; Szetu, John; Qoqonokana, Mundi Qalo; Ramke, Jacqueline

    2011-01-01

    To determine the prevalence and severity of diabetic eye disease among adults aged ≥40 years with unrecognized diabetes in Fiji. Population-based cross-sectional survey using multistage cluster random sampling. 1381 (=73.0% participation). Interview-based questionnaire; visual acuity measured; dilated ocular examination performed; glycosylated haemoglobin (HbA1c) concentration determined. Prevalence and grade of diabetic retinopathy/maculopathy. Sample prevalence of diabetes was 44.8% (95%CI 42.2-47.5%), with 63.4% (95%CI 59.5-67.1%) previously undiagnosed (384/606). Predictors of undiagnosed compared with previously diagnosed diabetes were female gender (P = 0.001), rural residence (P = 0.049) and not having a relative with known diabetes (P < 0.001). Twenty-two retinae of participants with previously undiagnosed diabetes were unexaminable (predominantly cataract). Of the remaining 746 eyes, 3.5% (95%CI 2.4-5.1%) had diabetic retinopathy/maculopathy, 1 (0.1%) had proliferative retinopathy and 4 (0.5%) had active significant maculopathy. Of eyes with diabetic disease, two (7.7%, 95%CI 1.0-25.3%) had diabetes-related vision impairment (3/60; 6/60). Sixteen previously undiagnosed participants (4.2%, 95%CI 2.5-6.7%) had diabetic disease evident in at least one eye: for four (all Melanesian women aged >50 years), this was vision-threatening (1.0%; 95%CI 0.3-2.8). Mean HbA1c (10.7 ± 2.6%) of participants undiagnosed and with diabetes eye disease was higher (P < 0.001) than that of those undiagnosed and without. The prevalence of diabetic eye disease was low among this cohort, but where present, severe vision-threatening retinopathy/maculopathy was relatively common. If diabetic eye disease is to be avoided or ameliorated in Fiji, then community awareness of and access to diabetes diagnostic services must improve, particularly for women and rural dwellers. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of

  9. A comparative study of family functioning, health, and mental health awareness and utilization among female Bedouin-Arabs from recognized and unrecognized villages in the Negev.

    PubMed

    Al-Krenawi, Alean; Graham, John R

    2006-02-01

    A good portion of geography is contested by the Israeli state and the country's Bedouin-Arab population. There are two categories of Bedouin villages: those areas that are "officially" recognized by the state and those that are not. In this article we determine utilization and awareness of health and mental health services among 376 Bedouin-Arab women in recognized and unrecognized villages in the Negev. Although there are differences between them, primary health care (PHC) services usually are available within recognized villages, accessible to those from unrecognized villages, and tend to precipitate user satisfaction. We conclude with various suggestions for improving health service delivery and making PHC and mental health delivery more accessible. Through this article we intend to help mental health practitioners on two levels: the policy level, regarding the design of mental health services for societies in transition, such as the Bedouin Arab, and the practical level by helping practitioners better appreciate the psychosocial status of women in Bedouin-Arab societies and the factors associated with Bedouin-Arab PHC utilization.

  10. Methylation array data can simultaneously identify individuals and convey protected health information: an unrecognized ethical concern.

    PubMed

    Philibert, Robert A; Terry, Nicolas; Erwin, Cheryl; Philibert, Winter J; Beach, Steven Rh; Brody, Gene H

    2014-01-01

    Genome-wide methylation arrays are increasingly used tools in studies of complex medical disorders. Because of their expense and potential utility to the scientific community, current federal policy dictates that data from these arrays, like those from genome-wide genotyping arrays, be deposited in publicly available databases. Unlike the genotyping information, access to the expression data is not restricted. An underlying supposition in the current nonrestricted access to methylation data is the belief that protected health and personal identifying information cannot be simultaneously extracted from these arrays. In this communication, we analyze methylation data from the Illumina HumanMethylation450 array and show that genotype at 1,069 highly informative loci, and both alcohol and smoking consumption information, can be derived from the array data. We conclude that both potentially personally identifying information and substance-use histories can be simultaneously derived from methylation array data. Because access to genetic information about a database subject or one of their relatives is critical to the de-identification process, this risk of de-identification is limited at the current time. We propose that access to genome-wide methylation data be restricted to institutionally approved investigators who accede to data use agreements prohibiting re-identification.

  11. Carving out turf in a biodiversity hotspot: multiple, previously unrecognized shrew species co-occur on Java Island, Indonesia.

    PubMed

    Esselstyn, Jacob A; Maharadatunkamsi; Achmadi, Anang S; Siler, Cameron D; Evans, Ben J

    2013-10-01

    In theory, competition among species in a shared habitat results in niche separation. In the case of small recondite mammals such as shrews, little is known about their autecologies, leaving open questions regarding the degree to which closely related species co-occur and how or whether ecological niches are partitioned. The extent to which species are able to coexist may depend on the degree to which they exploit different features of their habitat, which may in turn influence our ability to recognize them as species. We explored these issues in a biodiversity hotspot, by surveying shrew (genus Crocidura) diversity on the Indonesian island of Java. We sequenced portions of nine unlinked genes in 100-117 specimens of Javan shrews and incorporated homologous data from most known Crocidura species from other parts of island South-East Asia. Current taxonomy recognizes four Crocidura species on Java, including two endemics. However, our phylogenetic, population genetic and species delimitation analyses identify five species on the island, and all are endemic to Java. While the individual ranges of these species may not overlap in their entirety, we found up to four species living syntopically and all five species co-occurring on one mountain. Differences in species' body size, use of above ground-level habitats by one species and habitat partitioning along ecological gradients may have facilitated species diversification and coexistence. © 2013 John Wiley & Sons Ltd.

  12. Previously identified patellar tendinopathy risk factors differ between elite and sub-elite volleyball players.

    PubMed

    Janssen, I; Steele, J R; Munro, B J; Brown, N A T

    2015-06-01

    Patellar tendinopathy is the most common knee injury incurred in volleyball, with its prevalence in elite athletes more than three times that of their sub-elite counterparts. The purpose of this study was to determine whether patellar tendinopathy risk factors differed between elite and sub-elite male volleyball players. Nine elite and nine sub-elite male volleyball players performed a lateral stop-jump block movement. Maximum vertical jump, training history, muscle extensibility and strength, three-dimensional landing kinematics (250 Hz), along with lower limb neuromuscular activation patterns (1500 Hz), and patellar tendon loading were collected during each trial. Multivariate analyses of variance (P < 0.05) assessed for between-group differences in risk factors or patellar tendon loading. Significant interaction effects were further evaluated using post-hoc univariate analysis of variance tests. Landing kinematics, neuromuscular activation patterns, patellar tendon loading, and most of the previously identified risk factors did not differ between the elite and sub-elite players. However, elite players participated in a higher training volume and had less quadriceps extensibility than sub-elite players. Therefore, high training volume is likely the primary contributor to the injury discrepancy between elite and sub-elite volleyball players. Interventions designed to reduce landing frequency and improve quadriceps extensibility are recommended to reduce patellar tendinopathy prevalence in volleyball players. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Transcriptome Analysis of Mycobacteria-Specific CD4+ T Cells Identified by Activation-Induced Expression of CD154.

    PubMed

    Kunnath-Velayudhan, Shajo; Goldberg, Michael F; Saini, Neeraj K; Johndrow, Christopher T; Ng, Tony W; Johnson, Alison J; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A

    2017-10-01

    Analysis of Ag-specific CD4 + T cells in mycobacterial infections at the transcriptome level is informative but technically challenging. Although several methods exist for identifying Ag-specific T cells, including intracellular cytokine staining, cell surface cytokine-capture assays, and staining with peptide:MHC class II multimers, all of these have significant technical constraints that limit their usefulness. Measurement of activation-induced expression of CD154 has been reported to detect live Ag-specific CD4 + T cells, but this approach remains underexplored and, to our knowledge, has not previously been applied in mycobacteria-infected animals. In this article, we show that CD154 expression identifies adoptively transferred or endogenous Ag-specific CD4 + T cells induced by Mycobacterium bovis bacillus Calmette-Guérin vaccination. We confirmed that Ag-specific cytokine production was positively correlated with CD154 expression by CD4 + T cells from bacillus Calmette-Guérin-vaccinated mice and show that high-quality microarrays can be performed from RNA isolated from CD154 + cells purified by cell sorting. Analysis of microarray data demonstrated that the transcriptome of CD4 + CD154 + cells was distinct from that of CD154 - cells and showed major enrichment of transcripts encoding multiple cytokines and pathways of cellular activation. One notable finding was the identification of a previously unrecognized subset of mycobacteria-specific CD4 + T cells that is characterized by the production of IL-3. Our results support the use of CD154 expression as a practical and reliable method to isolate live Ag-specific CD4 + T cells for transcriptomic analysis and potentially for a range of other studies in infected or previously immunized hosts. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. High-throughput screening to identify selective inhibitors of microbial sulfate reduction (and beyond)

    NASA Astrophysics Data System (ADS)

    Carlson, H. K.; Coates, J. D.; Deutschbauer, A. M.

    2015-12-01

    The selective perturbation of complex microbial ecosystems to predictably influence outcomes in engineered and industrial environments remains a grand challenge for geomicrobiology. In some industrial ecosystems, such as oil reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which is toxic, explosive and corrosive. Current strategies to selectively inhibit sulfidogenesis are based on non-specific biocide treatments, bio-competitive exclusion by alternative electron acceptors or sulfate-analogs which are competitive inhibitors or futile/alternative substrates of the sulfate reduction pathway. Despite the economic cost of sulfidogenesis, there has been minimal exploration of the chemical space of possible inhibitory compounds, and very little work has quantitatively assessed the selectivity of putative souring treatments. We have developed a high-throughput screening strategy to target SRM, quantitatively ranked the selectivity and potency of hundreds of compounds and identified previously unrecognized SRM selective inhibitors and synergistic interactions between inhibitors. Once inhibitor selectivity is defined, high-throughput characterization of microbial community structure across compound gradients and identification of fitness determinants using isolate bar-coded transposon mutant libraries can give insights into the genetic mechanisms whereby compounds structure microbial communities. The high-throughput (HT) approach we present can be readily applied to target SRM in diverse environments and more broadly, could be used to identify and quantify the potency and selectivity of inhibitors of a variety of microbial metabolisms. Our findings and approach are relevant for engineering environmental ecosystems and also to understand the role of natural gradients in shaping microbial niche space.

  15. Prevalence of unrecognized dyslipidaemia in Dubai and Northern Emirates: a cross-sectional hospital based study.

    PubMed

    Vela, Barbara Karin; Alhessi, Alaaeldin Y; Popović, Marko; Al-Shaqra, Maryam A

    2008-12-01

    The aim of this study is to determine the prevalence of unrecognized dyslipidaemia and a specific correlation between lipid values and age, gender or ethnic origin in the study population. This retrospective cross-sectional study included 311 subjects who had their lipid profiles checked for the first time in a private hospital in Dubai in a six month - period. The analysis shows an increased prevalence of Low Density Lipoprotein (LDL) hypercholesterolemia with relatively higher Low Density Lipoprotein Cholesterol (LDL-c) values in male subjects (p < 0.016) as well as with the Middle East ethnic origin group (p < 0.025), while desirable High Density Lipoprotein (HDL-c) was found among female subjects (p = 0). The discordance between the percentages of elevated LDL-c and Total cholesterol (T-c) signifies the role of the LDL-c/non-HDL-c as the main surrogate for dyslipidaemia as a risk for atherosclerosis, and as a primary target of therapy.

  16. Previously unrecognized now-inactive strand of the North Anatolian fault in the Thrace basin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Perincek, D.

    1988-08-01

    The North Anatolian fault is a major 1,200 km-long transform fault bounding the Anatolian plate to the north. It formed in late middle Miocene time as a broad shear zone with a number of strands splaying westward in a horsetail fashion. Later, movement became localized along the stem, and the southerly and northerly splays became inactive. One such right-lateral, now-inactive splay is the west-northwest-striking Thrace strike-slip fault system, consisting of three subparallel strike-slip faults. From north to south these are the Kirklareli, Lueleburgaz, and Babaeski fault zones, extending {plus minus} 130 km along the strike. The Thrace fault zone probablymore » connected with the presently active northern strand of the North Anatolian fault in the Sea of Marmara in the southeast and may have joined the Plovdiv graben zone in Bulgaria in the northwest. The Thrace basin in which the Thrace fault system is located, is Cenozoic with a sedimentary basin fill from middle Eocene to Pliocene. The Thrace fault system formed in pre-Pliocene time and had become inactive by the Pliocene. Strike-slip fault zones with normal and reverse separation are detected by seismic reflection profiles and subsurface data. Releasing bend extensional structures (e.g., near the town of Lueleburgaz) and restraining bend compressional structures (near Vakiflar-1 well) are abundant on the fault zones. Umurca and Hamitabad fields are en echelon structures on the Lueleburgaz fault zone. The Thrace strike-slip fault system has itself a horsetail shape, the various strands of which become younger southward. The entire system died before the Pliocene, and motion on the North Anatolian fault zone began to be accommodated in the Sea of Marmara region. Thus the Thrace fault system represents the oldest strand of the North Anatolian fault in the west.« less

  17. Three cases of donor-derived pulmonary tuberculosis in lung transplant recipients and review of 12 previously reported cases: opportunities for early diagnosis and prevention.

    PubMed

    Mortensen, E; Hellinger, W; Keller, C; Cowan, L S; Shaw, T; Hwang, S; Pegues, D; Ahmedov, S; Salfinger, M; Bower, W A

    2014-02-01

    Solid organ transplant recipients have a higher frequency of tuberculosis (TB) than the general population, with mortality rates of approximately 30%. Although donor-derived TB is reported to account for <5% of TB in solid organ transplants, the source of Mycobacterium tuberculosis infection is infrequently determined. We report 3 new cases of pulmonary TB in lung transplant recipients attributed to donor infection, and review the 12 previously reported cases to assess whether cases could have been prevented and whether any cases that might occur in the future could be detected and investigated more quickly. Specifically, we evaluate whether opportunities existed to determine TB risk on the basis of routine donor history, to expedite diagnosis through routine mycobacterial smears and cultures of respiratory specimens early post transplant, and to utilize molecular tools to investigate infection sources epidemiologically. On review, donor TB risk was present among 7 cases. Routine smears and cultures diagnosed 4 asymptomatic cases. Genotyping was used to support epidemiologic findings in 6 cases. Validated screening protocols, including microbiological testing and newer technologies (e.g., interferon-gamma release assays) to identify unrecognized M. tuberculosis infection in deceased donors, are warranted. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Lack of in vitro constitutive activity for four previously reported TSH receptor mutations identified in patients with nonautoimmune hyperthyroidism and hot thyroid carcinomas.

    PubMed

    Jaeschke, Holger; Mueller, Sandra; Eszlinger, Markus; Paschke, Ralf

    2010-12-01

    Constitutively activating mutations (CAMs) of the TSHR are the major cause for nonautoimmune hyperthyroidism. Re-examination of constitutive activity previously determined in CHO cell lines recently demonstrated the caveats for the in vitro determination of constitutive TSHR activity, which leads to false positive conclusions regarding the molecular origin of hyperthyroidism or hot thyroid carcinomas. Mutations L677V and T620I identified in hot thyroid carcinomas were previously characterized in CHO and in 3T3-Vill cell lines, respectively, stably expressing the mutant without determination of TSHR expression. F666L identified in a patient with hot thyroid nodules, I691F in a family with nonautoimmune hyperthyroidism and F631I identified in a hot thyroid carcinoma were not characterized for their in vitro function. Therefore, we decided to (re)evaluate the in vitro function of these five TSHR variants by determination of cell surface expression, and intracellular cAMP and inositol phosphate levels and performed additionally linear regression analyses to determine basal activity independently from the mutant's cell surface expression in COS-7 and HEK(GT) cells. Only one (F631I) of the five investigated TSHR variants displayed constitutive activity for G(α) s signalling and showed correlation with the clinical phenotype. The previous false classification of T620I and L677V as CAMs is most likely related to the fact that both mutations were characterized in cell lines stably expressing the mutated receptor construct without assessing the respective receptor number per cell. Other molecular aetiologies for the nonautoimmune hyperthyroidism and/or hot thyroid carcinomas in these three patients and one family should be elucidated. © 2010 Blackwell Publishing Ltd.

  19. Hope: A Panacea Unrecognized

    PubMed Central

    Obayuwana, Alphonsus O.

    1980-01-01

    This paper identifies stress as a common and constant irritation to human homeostasis, evaluates the role of hope in the maintenance of health, and recommends a method of anticipatory care for securing optimum health for mankind. PMID:7373668

  20. Clinical expression of haemochromatosis in Irish C282Y homozygotes identified through family screening.

    PubMed

    Gleeson, F; Ryan, E; Barrett, S; Crowe, J

    2004-09-01

    In Ireland, the homozygote frequency of the C282Y mutation in the HFE gene is 1/83. The biochemical expression of this mutation is high in haemochromatosis (HH) individuals identified through family screening, but the clinical expression of the mutation in Irish HH subjects to date has not been investigated fully. To determine the clinical, biochemical and histological penetrance of the C282Y mutation in Irish C282Y homozygotes identified through family screening. Two hundred and nine C282Y homozygous individuals comprising of 172 first-degree relatives, 31 second-degree relatives and four unrelated individuals were identified following HFE mutation analysis of 167 families. The following variables were analysed: age at identification, gender, fasting transferrin saturation, fasting serum ferritin, liver enzymes, clinical symptomatology, liver histopathology and histochemical iron staining. An elevated transferrin saturation in combination with an elevated ferritin was present in 43.4% of males and 23.3% of females. Abnormal liver enzymes were found in 32.3% of males. Diabetes, a haemochromatosis-specific association, was noted in 2.8% of males. Of those individuals requiring liver histopathology evaluation, 38% had moderate-to-severe iron staining, and 42% had fibrosis; 2.8% of the biopsied cohort had cirrhosis. Thus, HH cirrhotics were identified in less than 1% of the screened population. Although the homozygote frequency in Ireland is very high, the prevalence of advanced liver disease was less than 1% of the family members screened. Nevertheless, 42% of biopsied patients had histological evidence of iron overload-related architectural change and 2.8% had cirrhosis. This cohort of young people had previously unrecognized biochemical iron overload and histopathological change. This emphasizes the importance and value of both genetic and biochemical screening in first-degree relatives of identified homozygotes.

  1. Optical Coherence Tomography Identifies Lower Labial Salivary Gland Surface Density in Cystic Fibrosis

    PubMed Central

    Nowak, Jan K.; Grulkowski, Ireneusz; Karnowski, Karol; Wojtkowski, Maciej; Walkowiak, Jaroslaw

    2015-01-01

    The labial minor salivary glands (LSGs) are easily accessible mucus-secreting structures of the alimentary tract that may provide new information on the basis of gastrointestinal complications of cystic fibrosis (CF). It was shown that they are destructed in the course of cystic fibrosis. We employed wide-field, micrometer resolution in vivo optical coherence tomography to assess the surface density of LSGs in 18 patients with CF and 18 healthy subjects. The median LSGs’ surface densities in CF patients, and in the control group were 4.32 glands/cm2 and 6.58 glands/cm2, respectively (p = 0.006; Mann-Whitney U test). A lower LSG surface density is a previously unrecognized CF-related pathology of the alimentary tract. PMID:25622042

  2. Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation

    PubMed Central

    Nollen, Ellen A. A.; Garcia, Susana M.; van Haaften, Gijs; Kim, Soojin; Chavez, Alejandro; Morimoto, Richard I.; Plasterk, Ronald H. A.

    2004-01-01

    Protein misfolding and the formation of aggregates are increasingly recognized components of the pathology of human genetic disease and hallmarks of many neurodegenerative disorders. As exemplified by polyglutamine diseases, the propensity for protein misfolding is associated with the length of polyglutamine expansions and age-dependent changes in protein-folding homeostasis, suggesting a critical role for a protein homeostatic buffer. To identify the complement of protein factors that protects cells against the formation of protein aggregates, we tested transgenic Caenorhabditis elegans strains expressing polyglutamine expansion yellow fluorescent protein fusion proteins at the threshold length associated with the age-dependent appearance of protein aggregation. We used genome-wide RNA interference to identify genes that, when suppressed, resulted in the premature appearance of protein aggregates. Our screen identified 186 genes corresponding to five principal classes of polyglutamine regulators: genes involved in RNA metabolism, protein synthesis, protein folding, and protein degradation; and those involved in protein trafficking. We propose that each of these classes represents a molecular machine collectively comprising the protein homeostatic buffer that responds to the expression of damaged proteins to prevent their misfolding and aggregation. PMID:15084750

  3. Using an epiphytic moss to identify previously unknown sources of atmospheric cadmium pollution

    Treesearch

    Geoffrey H. Donovan; Sarah E. Jovan; Demetrios Gatziolis; Igor Burstyn; Yvonne L. Michael; Michael C. Amacher; Vicente J. Monleon

    2016-01-01

    Urban networks of air-quality monitors are often too widely spaced to identify sources of air pollutants, especially if they do not disperse far from emission sources. The objectives of this study were to test the use of moss bio-indicators to develop a fine-scale map of atmospherically-derived cadmium and to identify the sources of cadmium in a complex urban setting....

  4. Apparent mineralcorticoid excess syndrome, an often forgotten or unrecognized cause of hypokalemia and hypertension: case report and appraisal of the pathophysiology.

    PubMed

    Bisogni, Valeria; Rossi, Gian Paolo; Calò, Lorenzo A

    2014-06-01

    The glicyrrhizic acid, contained in licorice, has a mineralcorticoid-like effect. Chronic excess intake of licorice induces the rare syndrome of "apparent mineralcorticoid excess", due to the inhibitory effect of glicyrrhizic acid on 11 β-hydroxysteroid dehydrogenase type 2 determining clinical/biochemical manifestations as resistant hypertension, metabolic alkalosis and severe hypokalemia. We report a typical clinical case of licorice abuse to emphasize the importance of a detailed anamnesis, which is essential for the diagnosis, avoid unnecessary and expensive investigations, and reduce the duration of hospitalization. We also provide an appraisal of the pathophysiology of "apparent mineralcorticoid excess" syndrome, still an often forgotten or unrecognized cause of hypokalemia and hypertension.

  5. Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene.

    PubMed

    Montero-Conde, Cristina; Leandro-Garcia, Luis J; Chen, Xu; Oler, Gisele; Ruiz-Llorente, Sergio; Ryder, Mabel; Landa, Iñigo; Sanchez-Vega, Francisco; La, Konnor; Ghossein, Ronald A; Bajorin, Dean F; Knauf, Jeffrey A; Riordan, Jesse D; Dupuy, Adam J; Fagin, James A

    2017-06-20

    Oncogenic RAS mutations are present in 15-30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with Hras G12V in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-Hras G12V mice. The thyroid tumors closely phenocopied the histological features of human RAS-driven, poorly differentiated thyroid cancers. Characterization of transposon insertion sites in the SB-induced tumors identified 45 recurrently mutated candidate cancer genes. These mutation profiles were remarkably concordant with mutated cancer genes identified in a large series of human poorly differentiated and anaplastic thyroid cancers screened by next-generation sequencing using the MSK-IMPACT panel of cancer genes, which we modified to include all SB candidates. The disrupted genes primarily clustered in chromatin remodeling functional nodes and in the PI3K pathway. ATXN7 , a component of a multiprotein complex with histone acetylase activity, scored as a significant SB hit. It was recurrently mutated in advanced human cancers and significantly co-occurred with RAS or NF1 mutations. Expression of ATXN7 mutants cooperated with oncogenic RAS to induce thyroid cell proliferation, pointing to ATXN7 as a previously unrecognized cancer gene.

  6. Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene

    PubMed Central

    Montero-Conde, Cristina; Leandro-Garcia, Luis J.; Chen, Xu; Oler, Gisele; Ruiz-Llorente, Sergio; Ryder, Mabel; Landa, Iñigo; Sanchez-Vega, Francisco; La, Konnor; Ghossein, Ronald A.; Bajorin, Dean F.; Knauf, Jeffrey A.; Riordan, Jesse D.; Dupuy, Adam J.; Fagin, James A.

    2017-01-01

    Oncogenic RAS mutations are present in 15–30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with HrasG12V in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-HrasG12V mice. The thyroid tumors closely phenocopied the histological features of human RAS-driven, poorly differentiated thyroid cancers. Characterization of transposon insertion sites in the SB-induced tumors identified 45 recurrently mutated candidate cancer genes. These mutation profiles were remarkably concordant with mutated cancer genes identified in a large series of human poorly differentiated and anaplastic thyroid cancers screened by next-generation sequencing using the MSK-IMPACT panel of cancer genes, which we modified to include all SB candidates. The disrupted genes primarily clustered in chromatin remodeling functional nodes and in the PI3K pathway. ATXN7, a component of a multiprotein complex with histone acetylase activity, scored as a significant SB hit. It was recurrently mutated in advanced human cancers and significantly co-occurred with RAS or NF1 mutations. Expression of ATXN7 mutants cooperated with oncogenic RAS to induce thyroid cell proliferation, pointing to ATXN7 as a previously unrecognized cancer gene. PMID:28584132

  7. Kidney transplantation from a mother with unrecognized Fabry disease to her son with low α-galactosidase A activity: A 14-year follow-up without enzyme replacement therapy.

    PubMed

    Odani, Keiko; Okumi, Masayoshi; Honda, Kazuho; Ishida, Hideki; Tanabe, Kazunari

    2016-07-01

    We report a case of kidney transplantation from mother to son, both of whom were likely to have had an unrecognized renal variant phenotype of Fabry disease. The patient was a 54-year-old man, with an unknown primary cause of end stage renal disease. He had no notable past medical history, other than end stage renal disease. He underwent living-related kidney transplantation from his mother at age 40 years. Foam cells in the glomeruli were identified on histology assessment of a 0-hour allograft biopsy, with zebra bodies identified in the glomerular visceral epithelial cells by electron microscopy. These findings were indicative of Fabry disease in the donated kidney. As a definitive diagnosis of Fabry's disease could not be confirmed, enzyme replacement therapy was not initiated. Thirteen years after kidney transplantation, the patient underwent left nephrectomy for a left renal tumour, with pathological findings of clear cell carcinoma, foam cells and zebra bodies in the native kidney. Detailed examinations identified low α-galactosidase A activity and mutation of the α-Gal A gene, confirming a diagnosis of a renal variant phenotype of Fabry disease. Histology of several allograft biopsies performed over the 14 years from the time of kidney transplantation revealed only moderate interstitial fibrosis and tubular atrophy, with no evidence of disease progression on electron microscopy, despite the presence of zebra bodies in the glomerular visceral epithelial cells. © 2016 Asian Pacific Society of Nephrology.

  8. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone.

    PubMed

    Marcu, M G; Chadli, A; Bouhouche, I; Catelli, M; Neckers, L M

    2000-11-24

    Heat shock protein 90 (Hsp90), one of the most abundant chaperones in eukaryotes, participates in folding and stabilization of signal-transducing molecules including steroid hormone receptors and protein kinases. The amino terminus of Hsp90 contains a non-conventional nucleotide-binding site, related to the ATP-binding motif of bacterial DNA gyrase. The anti-tumor agents geldanamycin and radicicol bind specifically at this site and induce destabilization of Hsp90-dependent client proteins. We recently demonstrated that the gyrase inhibitor novobiocin also interacts with Hsp90, altering the affinity of the chaperone for geldanamycin and radicicol and causing in vitro and in vivo depletion of key regulatory Hsp90-dependent kinases including v-Src, Raf-1, and p185(ErbB2). In the present study we used deletion/mutation analysis to identify the site of interaction of novobiocin with Hsp90, and we demonstrate that the novobiocin-binding site resides in the carboxyl terminus of the chaperone. Surprisingly, this motif also recognizes ATP, and ATP and novobiocin efficiently compete with each other for binding to this region of Hsp90. Novobiocin interferes with association of the co-chaperones Hsc70 and p23 with Hsp90. These results identify a second site on Hsp90 where the binding of small molecule inhibitors can significantly impact the function of this chaperone, and they support the hypothesis that both amino- and carboxyl-terminal domains of Hsp90 interact to modulate chaperone activity.

  9. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

    PubMed Central

    Gasse, Barbara; Prasad, Megana; Delgado, Sidney; Huckert, Mathilde; Kawczynski, Marzena; Garret-Bernardin, Annelyse; Lopez-Cazaux, Serena; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Stoetzel, Corinne; Bloch-Zupan, Agnès; Sire, Jean-Yves

    2017-01-01

    Amelogenesis imperfecta (AI) designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20) produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI. PMID:28659819

  10. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta.

    PubMed

    Gasse, Barbara; Prasad, Megana; Delgado, Sidney; Huckert, Mathilde; Kawczynski, Marzena; Garret-Bernardin, Annelyse; Lopez-Cazaux, Serena; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Stoetzel, Corinne; Bloch-Zupan, Agnès; Sire, Jean-Yves

    2017-01-01

    Amelogenesis imperfecta (AI) designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene ( MMP20 ) produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI.

  11. CXCL5 is a Novel Mediator of Prostate Cancer Proliferation and Migration/Invasion

    DTIC Science & Technology

    2008-06-01

    such as Crohn disease , ulcerative colitis, and acute appendicitis, and by the exocrine tissue of the pancreas associated with chronic pancreatitis [9... disease , and may act as a previously unrecognized growth factor that promotes prostate cancer cell proliferation and migration/invasion. The major...proliferative prostatic disease , and may act as a previously unrecognized growth factor that promotes prostate cancer cell proliferation and migration

  12. Fat, demented and stupid: An unrecognized legacy of pediatric urology?

    PubMed

    Cooper, Christopher S

    2017-08-01

    The human body is an unfathomably intricate structure consisting of many connected and intertwined systems. This makes it impossible for therapeutic interventions to selectively target only one physiologic system without some impact or side effects on all the other systems. The resiliency of the human body modifies and disguises side effects, some of which may be undetectable for years and not apparent without scientific investigation. Pediatric urologists employ relatively few medications for the common conditions they treat and in general these consist of antibiotics, anticholinergics, and anesthetics. Although harm from early side effects is well recognized, recent medical literature suggests there may be other side effects of these common interventions that aren't as well recognized. Antibiotics have been added to livestock feed as growth promoters for three-quarters of a century. Antibiotics alter the microbiota of the intestinal tract and these alterations have been demonstrated to impact growth, metabolism, and the risk of obesity in animals and humans. To date, the long-term impact of daily antibiotic prophylaxis in children with such pediatric urology conditions as vesicoureteral reflux or prenatal hydronephrosis have not been published. Similarly, there are no studies assessing long-term effects of anticholinergic use on cognition in children despite research demonstrating an increased risk of dementia in adults using anticholinergics. Research in animals and children recently led the FDA to issue a warning regarding the risk of lengthy use of general anesthesia on cognitive development in children. This review raises the possibility that antibiotics in children may alter growth, anticholinergics may increase their risk of dementia later in life, and anesthetics may impair their cognitive development. The possibility of such an unrecognized legacy from current therapeutic interventions should give all physicians, including pediatric urologists, pause for

  13. A Cluster of Legionella-Associated Pneumonia Cases in a Population of Military Recruits

    DTIC Science & Technology

    2007-06-01

    this cluster may suggest a previously unrecognized suscep- FIG. 1. Phylogenic analysis of the training center strain (represented by the MCRD consensus...military recruits during population- based surveillance for pneumonia pathogens. Results were confirmed by sequence analysis . Cases cluster tightly...17 April 2007 A Legionella cluster was identified through retrospective PCR analysis of 240 throat swab samples from X-ray-confirmed pneumonia cases

  14. Multicenter Outbreak of Infections by Saprochaete clavata, an Unrecognized Opportunistic Fungal Pathogen

    PubMed Central

    Vaux, Sophie; Criscuolo, Alexis; Desnos-Ollivier, Marie; Diancourt, Laure; Tarnaud, Chloé; Vandenbogaert, Matthias; Brisse, Sylvain; Coignard, Bruno; Garcia-Hermoso, Dea; Blanc, Catherine; Hoinard, Damien; Lortholary, Olivier; Bretagne, Stéphane; Thiolet, Jean-Michel; de Valk, Henriette; Courbil, Rémi; Chabanel, Anne; Simonet, Marion; Maire, Francoise; Jbilou, Saadia; Tiberghien, Pierre; Blanchard, Hervé; Venier, Anne-Gaëlle; Bernet, Claude; Simon, Loïc; Sénéchal, Hélène; Pouchol, Elodie; Angot, Christiane; Ribaud, Patricia; Socié, G.; Flèche, M.; Brieu, Nathalie; Lagier, Evelyne; Chartier, Vanessa; Allegre, Thierry; Maulin, Laurence; Lanic, Hélène; Tilly, Hervé; Bouchara, Jean-Philippe; Pihet, Marc; Schmidt, Aline; Kouatchet, Achille; Vandamme, Yves-Marie; Ifrah, Norbert; Mercat, Alain; Accoceberry, Isabelle; Albert, Olivier; Leguay, Thibaut; Rogues, Anne-Marie; Bonhomme, Julie; Reman, Oumédaly; Lesteven, Claire; Poirier, Philippe; Chabrot, Cécile Molucon; Calvet, Laure; Baud, Olivier; Cambon, Monique; Farkas, Jean Chistophe; Lafon, Bruno; Dalle, Frédéric; Caillot, Denis; Lazzarotti, Aline; Aho, Serge; Combret, Sandrine; Facon, Thierry; Sendid, Boualem; Loridant, Séverine; Louis, Terriou; Cazin, Bruno; Grandbastien, Bruno; Bourgeois, Nathalie; Lotthé, Anne; Cartron, Guillaume; Ravel, Christophe; Colson, Pascal; Gaudard, Philippe; Bonmati, Caroline; Simon, Loic; Rabaud, Christian; Machouart, Marie; Poisson, Didier; Carp, Diana; Meunier, Jérôme; Gaschet, Anne; Miquel, Chantal; Sanhes, Laurence; Ferreyra, Milagros; Leibinger, Franck; Geudet, Philippe; Toubas, Dominique; Himberlin, Chantal; Bureau-Chalot, Florence; Delmer, Alain; Favennec, Loïc; Gargala, Gilles; Michot, Jean-Baptiste; Girault, Christophe; David, Marion; Leprêtre, Stéphane; Jardin, Fabrice; Honderlick, Pierre; Caille, Vincent; Cerf, Charles; Cassaing, Sophie; Recher, Christian; Picard, Muriel; Protin, Caroline; Huguet, Françoise; Huynh, Anne; Ruiz, Jean; Riu-Poulenc, Béatrice; Letocart, Philippe; Marchou, Bruno; Verdeil, Xavier; Cavalié, Laurent; Chauvin, Pamela; Iriart, Xavier; Valentin, Alexis; Bouvet, Emmanuelle; Delmas-Marsalet, Béatrice; Jeblaoui, Asma; Kassis-Chikhani, Najiby; Mühlethaler, Konrad; Zimmerli, Stefan; Zalar, Polona; Sánchez-Reus, Ferran; Gurgui, Merce

    2014-01-01

    ABSTRACT Rapidly fatal cases of invasive fungal infections due to a fungus later identified as Saprochaete clavata were reported in France in May 2012. The objectives of this study were to determine the clonal relatedness of the isolates and to investigate possible sources of contamination. A nationwide alert was launched to collect cases. Molecular identification methods, whole-genome sequencing (WGS), and clone-specific genotyping were used to analyze recent and historical isolates, and a case-case study was performed. Isolates from thirty cases (26 fungemias, 22 associated deaths at day 30) were collected between September 2011 and October 2012. Eighteen cases occurred within 8 weeks (outbreak) in 10 health care facilities, suggesting a common source of contamination, with potential secondary cases. Phylogenetic analysis identified one clade (clade A), which accounted for 16/18 outbreak cases. Results of microbiological investigations of environmental, drug, or food sources were negative. Analysis of exposures pointed to a medical device used for storage and infusion of blood products, but no fungal contamination was detected in the unused devices. Molecular identification of isolates from previous studies demonstrated that S. clavata can be found in dairy products and has already been involved in monocentric outbreaks in hematology wards. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen. This report also underlines further the potential of WGS for investigation of outbreaks due to uncommon fungal pathogens. PMID:25516620

  15. Mutagenesis Screen Identifies agtpbp1 and eps15L1 as Essential for T lymphocyte Development in Zebrafish.

    PubMed

    Seiler, Christoph; Gebhart, Nichole; Zhang, Yong; Shinton, Susan A; Li, Yue-sheng; Ross, Nicola L; Liu, Xingjun; Li, Qin; Bilbee, Alison N; Varshney, Gaurav K; LaFave, Matthew C; Burgess, Shawn M; Balciuniene, Jorune; Balciunas, Darius; Hardy, Richard R; Kappes, Dietmar J; Wiest, David L; Rhodes, Jennifer

    2015-01-01

    Genetic screens are a powerful tool to discover genes that are important in immune cell development and function. The evolutionarily conserved development of lymphoid cells paired with the genetic tractability of zebrafish make this a powerful model system for this purpose. We used a Tol2-based gene-breaking transposon to induce mutations in the zebrafish (Danio rerio, AB strain) genome, which served the dual purpose of fluorescently tagging cells and tissues that express the disrupted gene and provided a means of identifying the disrupted gene. We identified 12 lines in which hematopoietic tissues expressed green fluorescent protein (GFP) during embryonic development, as detected by microscopy. Subsequent analysis of young adult fish, using a novel approach in which single cell suspensions of whole fish were analyzed by flow cytometry, revealed that 8 of these lines also exhibited GFP expression in young adult cells. An additional 15 lines that did not have embryonic GFP+ hematopoietic tissue by microscopy, nevertheless exhibited GFP+ cells in young adults. RT-PCR analysis of purified GFP+ populations for expression of T and B cell-specific markers identified 18 lines in which T and/or B cells were fluorescently tagged at 6 weeks of age. As transposon insertion is expected to cause gene disruption, these lines can be used to assess the requirement for the disrupted genes in immune cell development. Focusing on the lines with embryonic GFP+ hematopoietic tissue, we identified three lines in which homozygous mutants exhibited impaired T cell development at 6 days of age. In two of the lines we identified the disrupted genes, agtpbp1 and eps15L1. Morpholino-mediated knockdown of these genes mimicked the T cell defects in the corresponding mutant embryos, demonstrating the previously unrecognized, essential roles of agtpbp1 and eps15L1 in T cell development.

  16. Identifying Threshold Concepts for Information Literacy: A Delphi Study

    ERIC Educational Resources Information Center

    Townsend, Lori; Hofer, Amy R.; Hanick, Silvia Lin; Brunetti, Korey

    2016-01-01

    This study used the Delphi method to engage expert practitioners on the topic of threshold concepts--core ideas and processes in a discipline that students need to grasp in order to progress in their learning, but that are often unspoken or unrecognized by expert practitioners--for information literacy. A panel of experts considered two questions:…

  17. Retrograde air escape via the nasolacrimal system: a previously unrecognized complication of continuous positive airway pressure in the management of obstructive sleep apnea.

    PubMed

    Singh, Narinder Pal; Walker, Robbie James Eades; Cowan, Fiona; Davidson, Arthur Craig; Roberts, David Newton

    2014-05-01

    Continuous positive airway pressure (CPAP) is the gold standard treatment for moderate to severe obstructive sleep apnoea (OSA). Eye-related side effects of CPAP are commonly attributed to a poorly sealed mask, allowing leaked air to blow over the eye. We present 3 cases where attended polysomnography (A-PSG) demonstrated CPAP-associated retrograde air escape via the nasolacrimal system (CRANS) in the absence of any mask leaks. Symptoms included dry eye, epiphora, air escape from the medial canthus, and eyelid flutter. Symptoms were controlled with a variety of surgical and nonsurgical techniques. CRANS represents a previously undescribed clinical entity. CRANS may be responsible for some CPAP-related eye side effects and possibly for rarer secondary eye complications, including conjunctivitis and corneal ulceration. CRANS should be suspected in any patient on CPAP complaining of eye symptoms. CRANS may be diagnosed through careful observation during A-PSG and confirmed by performing a "saline bubble test." Management options include nonsurgical (mask alternatives, humidification, nasopharyngeal airway) and surgical techniques (nasal airway surgery, inferior turbinate out-fracture and adhesion, injection of bulking agent around Hasner's valve).

  18. Environmental hazards of waste disposal patterns--a multimethod study in an unrecognized Bedouin village in the Negev area of Israel.

    PubMed

    Meallem, Ilana; Garb, Yaakov; Cwikel, Julie

    2010-01-01

    The Bedouin of the Negev region of Israel are a formerly nomadic, indigenous, ethnic minority, of which 40% currently live in unrecognized villages without organized, solid waste disposal. This study, using both quantitative and qualitative methods, explored the transition from traditional rubbish production and disposal to current uses, the current composition of rubbish, methods of waste disposal, and the extent of exposure to waste-related environmental hazards in the village of Um Batim. The modern, consumer lifestyle produced both residential and construction waste that was dumped very close to households. Waste was tended to by women who predominantly used backyard burning for disposal, exposing villagers to corrosive, poisonous, and dangerously flammable items at these burn sites. Village residents expressed a high level of concern over environmental hazards, yet no organized waste disposal or environmental hazards reduction was implemented.

  19. Proteome and metabolome profiling of cytokinin action in Arabidopsis identifying both distinct and similar responses to cytokinin down- and up-regulation.

    PubMed

    Černý, Martin; Kuklová, Alena; Hoehenwarter, Wolfgang; Fragner, Lena; Novák, Ondrej; Rotková, Gabriela; Jedelsky, Petr L; Žáková, Katerina; Šmehilová, Mária; Strnad, Miroslav; Weckwerth, Wolfram; Brzobohaty, Bretislav

    2013-11-01

    In plants, numerous developmental processes are controlled by cytokinin (CK) levels and their ratios to levels of other hormones. While molecular mechanisms underlying the regulatory roles of CKs have been intensely researched, proteomic and metabolomic responses to CK deficiency are unknown. Transgenic Arabidopsis seedlings carrying inducible barley cytokinin oxidase/dehydrogenase (CaMV35S>GR>HvCKX2) and agrobacterial isopentenyl transferase (CaMV35S>GR>ipt) constructs were profiled to elucidate proteome- and metabolome-wide responses to down- and up-regulation of CK levels, respectively. Proteome profiling identified >1100 proteins, 155 of which responded to HvCKX2 and/or ipt activation, mostly involved in growth, development, and/or hormone and light signalling. The metabolome profiling covered 79 metabolites, 33 of which responded to HvCKX2 and/or ipt activation, mostly amino acids, carbohydrates, and organic acids. Comparison of the data sets obtained from activated CaMV35S>GR>HvCKX2 and CaMV35S>GR>ipt plants revealed unexpectedly extensive overlaps. Integration of the proteomic and metabolomic data sets revealed: (i) novel components of molecular circuits involved in CK action (e.g. ribosomal proteins); (ii) previously unrecognized links to redox regulation and stress hormone signalling networks; and (iii) CK content markers. The striking overlaps in profiles observed in CK-deficient and CK-overproducing seedlings might explain surprising previously reported similarities between plants with down- and up-regulated CK levels.

  20. Posttransfusion purpura associated with an autoantibody directed against a previously undefined platelet antigen.

    PubMed

    Stricker, R B; Lewis, B H; Corash, L; Shuman, M A

    1987-05-01

    Although alloantibody against the PLA1 platelet antigen is usually found in patients with posttransfusion purpura (PTP), the mechanism of destruction of the patient's own PLA1-negative platelets is unexplained. We used a sensitive immunoblot technique to detect antiplatelet antibodies in a patient with classic PTP. The patient's acute-phase serum contained antibodies against three proteins present in control (PLA1-positive) platelets: an antibody that bound to a previously unrecognized platelet protein of mol wt 120,000 [glycoprotein (GP) 120], antibodies that bound to PLA1 (mol wt 90,000), and an epitope of GP IIb (mol wt 140,000). The antibodies against PLA1 and GP IIb did not react with the patient's own PLA1-negative platelets, control PLA1-negative platelets, or thrombasthenic platelets. In contrast, the antibody against GP 120 recognized this protein in all three platelet preparations, but not in Bernard-Soulier or Leka (Baka)-negative platelets. Antibody against GP 120 was not detected in the patient's recovery serum, although the antibodies against PLA1 and GP IIb persisted. F(ab)2 prepared from the patient's acute-phase serum also bound to GP 120. These results suggest that in PTP, transient autoantibody production may be responsible for autologous (PLA1-negative) platelet destruction. In addition, alloantibodies against more than one platelet alloantigen may be found in this disease. The nature of the GP 120 autoantigen and the GP IIb-related alloantigen defined by our patient's serum remains to be determined.

  1. Assessment tools for unrecognized myocardial infarction: a cross-sectional analysis of the REasons for geographic and racial differences in stroke population

    PubMed Central

    2013-01-01

    Background Routine electrocardiograms (ECGs) are not recommended for asymptomatic patients because the potential harms are thought to outweigh any benefits. Assessment tools to identify high risk individuals may improve the harm versus benefit profile of screening ECGs. In particular, people with unrecognized myocardial infarction (UMI) have elevated risk for cardiovascular events and death. Methods Using logistic regression, we developed a basic assessment tool among 16,653 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study using demographics, self-reported medical history, blood pressure, and body mass index and an expanded assessment tool using information on 51 potential variables. UMI was defined as electrocardiogram evidence of myocardial infarction without a self-reported history (n = 740). Results The basic assessment tool had a c-statistic of 0.638 (95% confidence interval 0.617 - 0.659) and included age, race, smoking status, body mass index, systolic blood pressure, and self-reported history of transient ischemic attack, deep vein thrombosis, falls, diabetes, and hypertension. A predicted probability of UMI > 3% provided a sensitivity of 80% and a specificity of 30%. The expanded assessment tool had a c-statistic of 0.654 (95% confidence interval 0.634-0.674). Because of the poor performance of these assessment tools, external validation was not pursued. Conclusions Despite examining a large number of potential correlates of UMI, the assessment tools did not provide a high level of discrimination. These data suggest defining groups with high prevalence of UMI for targeted screening will be difficult. PMID:23530553

  2. Grouping Parturients by Parity, Previous-Cesarean, and Mode of Delivery (P-C-MoD Classification) Better Identifies Groups at Risk for Postpartum Hemorrhage.

    PubMed

    Reichman, Orna; Gal, Micahel; Sela, Hen Y; Khayyat, Izzat; Emanuel, Michael; Samueloff, Arnon

    2016-10-01

    Objective We aimed to create a clinical classification to better identify parturients at risk for postpartum hemorrhage (PPH). Method A retrospective cohort, including all women who delivered at a single tertiary care medical center, between 2006 and 2014. Parturients were grouped by parity and history of cesarean delivery (CD): primiparas, multipara, and multipara with previous CD. Each were further subgrouped by mode of delivery (spontaneous vaginal delivery [SVD], operative vaginal delivery [OVD], emergency or elective CD). In all, 12 subgroups, based on parity, previous cesarean, and mode of delivery, formed the P-C-MoD classification. PPH was defined as a decrease of ≥3 gram% hemoglobin from admission and/or transfusion of blood products. Univariate analysis followed by multivariate analysis was performed to assess risk for PPH, controlling for confounders. Results The crude rate of PPH among 126,693 parturients was 7%. The prevalence differed significantly among independent risk factors: primiparity, 14%; multiparity, 4%; OVD, 22%; and CD, 15%. The P-C-MoD classification, segregated better between parturients at risk for PPH. The prevalence of PPH was highest for primiparous undergoing OVD (27%) compared with multiparous with SVD (3%), odds ratio [OR] = 12.8 (95% confidence interval [CI],11.9-13.9). These finding were consistent in the multivariate analysis OR = 13.1 (95% CI,12.1-14.3). Conclusion Employing the P-C-MoD classification more readily identifies parturients at risk for PPH and is superior to estimations based on single risk factors. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Parking lot sealcoat: An unrecognized source of urban polycyclic aromatic hydrocarbons

    USGS Publications Warehouse

    Mahler, B.J.; Van Metre, P.C.; Bashara, T.J.; Wilson, J.T.; Johns, D.A.

    2005-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are a ubiquitous contaminant in urban environments. Although numerous sources of PAHs to urban runoff have been identified, their relative importance remains uncertain. We show that a previously unidentified source of urban PAHs, parking lot sealcoat, may dominate loading of PAHs to urban water bodies in the United States. Particles in runoff from parking lots with coal-tar emulsion sealcoat had mean concentrations of PAHs of 3500 mg/kg, 65 times higher than the mean concentration from unsealed asphalt and cement lots. Diagnostic ratios of individual PAHs indicating sources are similar for particles from coal-tar emulsion sealed lots and suspended sediment from four urban streams. Contaminant yields projected to the watershed scale for the four associated watersheds indicate that runoff from sealed parking lots could account for the majority of stream PAH loads.

  4. Multicenter outbreak of infections by Saprochaete clavata, an unrecognized opportunistic fungal pathogen.

    PubMed

    Vaux, Sophie; Criscuolo, Alexis; Desnos-Ollivier, Marie; Diancourt, Laure; Tarnaud, Chloé; Vandenbogaert, Matthias; Brisse, Sylvain; Coignard, Bruno; Dromer, Françoise

    2014-12-16

    Rapidly fatal cases of invasive fungal infections due to a fungus later identified as Saprochaete clavata were reported in France in May 2012. The objectives of this study were to determine the clonal relatedness of the isolates and to investigate possible sources of contamination. A nationwide alert was launched to collect cases. Molecular identification methods, whole-genome sequencing (WGS), and clone-specific genotyping were used to analyze recent and historical isolates, and a case-case study was performed. Isolates from thirty cases (26 fungemias, 22 associated deaths at day 30) were collected between September 2011 and October 2012. Eighteen cases occurred within 8 weeks (outbreak) in 10 health care facilities, suggesting a common source of contamination, with potential secondary cases. Phylogenetic analysis identified one clade (clade A), which accounted for 16/18 outbreak cases. Results of microbiological investigations of environmental, drug, or food sources were negative. Analysis of exposures pointed to a medical device used for storage and infusion of blood products, but no fungal contamination was detected in the unused devices. Molecular identification of isolates from previous studies demonstrated that S. clavata can be found in dairy products and has already been involved in monocentric outbreaks in hematology wards. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen. This report also underlines further the potential of WGS for investigation of outbreaks due to uncommon fungal pathogens. Several cases of rapidly fatal infections due to the fungus Saprochaete clavata were reported in France within a short period of time in three health care facilities, suggesting a common source of contamination. A nationwide alert collected 30 cases over 1 year

  5. Parking lot sealcoat: an unrecognized source of urban polycyclic aromatic hydrocarbons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barbara J. Mahler; Peter C. Van Metre; Thomas J. Bashara

    2005-08-01

    Polycyclic aromatic hydrocarbons (PAHs) are a ubiquitous contaminant in urban environments. Although numerous sources of PAHs to urban runoff have been identified, their relative importance remains uncertain. The authors show that a previously unidentified source of urban PAHs, parking lot sealcoat, may dominate loading of PAHs to urban water bodies in the United States. Particles in runoff from parking lots with coal-tar emulsion sealcoat had mean concentrations of PAHs of 3500 mg/kg, 65 times higher than the mean concentration from unsealed asphalt and cement lots. Diagnostic ratios of individual PAHs indicating sources are similar for particles from coal-tar emulsion sealedmore » lots and suspended sediment from four urban streams. Contaminant yields projected to the watershed scale for the four associated watersheds indicate that runoff from sealed parking lots could account for the majority of stream PAH loads. 35 refs., 6 figs., 2 tabs.« less

  6. Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish

    PubMed Central

    Monteiro, Diana A.; Taylor, Edwin W.; Sartori, Marina R.; Cruz, André L.; Rantin, Francisco T.; Leite, Cleo A. C.

    2018-01-01

    The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems. PMID:29507882

  7. Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish.

    PubMed

    Monteiro, Diana A; Taylor, Edwin W; Sartori, Marina R; Cruz, André L; Rantin, Francisco T; Leite, Cleo A C

    2018-02-01

    The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems.

  8. A Predictive Model Has Identified Tick-Borne Encephalitis High-Risk Areas in Regions Where No Cases Were Reported Previously, Poland, 1999-2012.

    PubMed

    Stefanoff, Pawel; Rubikowska, Barbara; Bratkowski, Jakub; Ustrnul, Zbigniew; Vanwambeke, Sophie O; Rosinska, Magdalena

    2018-04-04

    During 1999–2012, 77% of the cases of tick-borne encephalitis (TBE) were recorded in two out of 16 Polish provinces. However, historical data, mostly from national serosurveys, suggest that the disease could be undetected in many areas. The aim of this study was to identify which routinely-measured meteorological, environmental, and socio-economic factors are associated to TBE human risk across Poland, with a particular focus on areas reporting few cases, but where serosurveys suggest higher incidence. We fitted a zero-inflated Poisson model using data on TBE incidence recorded in 108 NUTS-5 administrative units in high-risk areas over the period 1999–2012. Subsequently we applied the best fitting model to all Polish municipalities. Keeping the remaining variables constant, the predicted rate increased with the increase of air temperature over the previous 10–20 days, precipitation over the previous 20–30 days, in forestation, forest edge density, forest road density, and unemployment. The predicted rate decreased with increasing distance from forests. The map of predicted rates was consistent with the established risk areas. It predicted, however, high rates in provinces considered TBE-free. We recommend raising awareness among physicians working in the predicted high-risk areas and considering routine use of household animal surveys for risk mapping.

  9. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.

    PubMed

    Wong, Vanessa K; Baker, Stephen; Pickard, Derek J; Parkhill, Julian; Page, Andrew J; Feasey, Nicholas A; Kingsley, Robert A; Thomson, Nicholas R; Keane, Jacqueline A; Weill, François-Xavier; Edwards, David J; Hawkey, Jane; Harris, Simon R; Mather, Alison E; Cain, Amy K; Hadfield, James; Hart, Peter J; Thieu, Nga Tran Vu; Klemm, Elizabeth J; Glinos, Dafni A; Breiman, Robert F; Watson, Conall H; Kariuki, Samuel; Gordon, Melita A; Heyderman, Robert S; Okoro, Chinyere; Jacobs, Jan; Lunguya, Octavie; Edmunds, W John; Msefula, Chisomo; Chabalgoity, Jose A; Kama, Mike; Jenkins, Kylie; Dutta, Shanta; Marks, Florian; Campos, Josefina; Thompson, Corinne; Obaro, Stephen; MacLennan, Calman A; Dolecek, Christiane; Keddy, Karen H; Smith, Anthony M; Parry, Christopher M; Karkey, Abhilasha; Mulholland, E Kim; Campbell, James I; Dongol, Sabina; Basnyat, Buddha; Dufour, Muriel; Bandaranayake, Don; Naseri, Take Toleafoa; Singh, Shalini Pravin; Hatta, Mochammad; Newton, Paul; Onsare, Robert S; Isaia, Lupeoletalalei; Dance, David; Davong, Viengmon; Thwaites, Guy; Wijedoru, Lalith; Crump, John A; De Pinna, Elizabeth; Nair, Satheesh; Nilles, Eric J; Thanh, Duy Pham; Turner, Paul; Soeng, Sona; Valcanis, Mary; Powling, Joan; Dimovski, Karolina; Hogg, Geoff; Farrar, Jeremy; Holt, Kathryn E; Dougan, Gordon

    2015-06-01

    The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.

  10. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events

    PubMed Central

    Wong, Vanessa K; Baker, Stephen; Pickard, Derek J; Parkhill, Julian; Page, Andrew J; Feasey, Nicholas A; Kingsley, Robert A; Thomson, Nicholas R; Keane, Jacqueline A; Weill, François-Xavier; Edwards, David J; Hawkey, Jane; Harris, Simon R; Mather, Alison E; Cain, Amy K; Hadfield, James; Hart, Peter J; Thieu, Nga Tran Vu; Klemm, Elizabeth J; Glinos, Dafni A; Breiman, Robert F; Watson, Conall H; Kariuki, Samuel; Gordon, Melita A; Heyderman, Robert S; Okoro, Chinyere; Jacobs, Jan; Lunguya, Octavie; Edmunds, W John; Msefula, Chisomo; Chabalgoity, Jose A; Kama, Mike; Jenkins, Kylie; Dutta, Shanta; Marks, Florian; Campos, Josefina; Thompson, Corinne; Obaro, Stephen; MacLennan, Calman A; Dolecek, Christiane; Keddy, Karen H; Smith, Anthony M; Parry, Christopher M; Karkey, Abhilasha; Mulholland, E Kim; Campbell, James I; Dongol, Sabina; Basnyat, Buddha; Dufour, Muriel; Bandaranayake, Don; Naseri, Take Toleafoa; Singh, Shalini Pravin; Hatta, Mochammad; Newton, Paul; Onsare, Robert S; Isaia, Lupeoletalalei; Dance, David; Davong, Viengmon; Thwaites, Guy; Wijedoru, Lalith; Crump, John A; De Pinna, Elizabeth; Nair, Satheesh; Nilles, Eric J; Thanh, Duy Pham; Turner, Paul; Soeng, Sona; Valcanis, Mary; Powling, Joan; Dimovski, Karolina; Hogg, Geoff; Farrar, Jeremy; Holt, Kathryn E; Dougan, Gordon

    2016-01-01

    The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species. PMID:25961941

  11. Cholesterol embolism: still an unrecognized entity with a high mortality rate.

    PubMed

    Jucgla, Anna; Moreso, Francesc; Muniesa, Cristina; Moreno, Abelardo; Vidaller, Antonio

    2006-11-01

    Cholesterol embolism (CE) is an increasingly common but often underdiagnosed medical problem. The recognition of clinical manifestations of CE is the first step toward a correct diagnosis. Our aim was to characterize the features of CE and the risk factors for fatal outcome. Clinical records of patients with clinical and histopathologic diagnoses of CE seen from January 1993 through March 2003 were reviewed. Twenty-six male patients were identified. Mean age was 64 years (range, 48-88 years). All patients had two or more risk factors for atherosclerosis. All but one patient had preexisting symptomatic atherosclerotic disease. At least one precipitating factor was identified in 23 patients (88%). Diagnosis of CE at admission was made in 9 patients only (35%). Cutaneous lesions (88%) and renal failure (73%) were the most common clinical findings. Complications (dialysis, acute pulmonary edema, amputation, or gastrointestinal surgery) were present in 21 patients (81%), and 15 patients died (58%). Previous chronic renal failure was the only variable associated with mortality (relative risk: 4.54, 95% confidence interval 1.26-16.6; P = .02). The results were obtained from patients admitted to a university hospital. This fact may have selected a higher proportion of severe cases. CE was frequently misdiagnosed. Skin lesions were the most common clinical findings and skin biopsy provided histologic confirmation in most of the patients. Chronic renal failure was the only factor related to death.

  12. WORKER INHALATION DOSE COEFFICIENTS FOR RADIONUCLIDES NOT PREVIOUSLY IDENTIFIED IN ICRP PUBLICATION 68

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McLaughlin, David A; Schwahn, Scott O

    2011-01-01

    While inhalation dose coefficients are provided for about 800 radionuclides in International Commission on Radiological Protection (ICRP) Publication 68, many radionuclides of practical dosimetric interest for facilities such as high-energy proton accelerators are not specifically addressed, nor are organ-specific dose coefficients tabulated. The ICRP Publication 68 methodology is used, along with updated radiological decay data and metabolic data, to identify committed equivalent dose coefficients [hT(50)] and committed effective dose coefficients [e(50)] for radionuclides produced at the Oak Ridge National Laboratory s Spallation Neutron Source.

  13. The long-term risk of recognized and unrecognized myocardial infarction for depression in older men.

    PubMed

    Jovanova, O; Luik, A I; Leening, M J G; Noordam, R; Aarts, N; Hofman, A; Franco, O H; Dehghan, A; Tiemeier, H

    2016-07-01

    The association between myocardial infarction (MI) and depression is well described. Yet, the underlying mechanisms are unclear and the contribution of psychological factors is uncertain. We aimed to determine the risk of recognized (RMI) and unrecognized (UMI) myocardial infections on depression, as both have a similar impact on cardiovascular health but differ in psychological epiphenomena. Participants of the Rotterdam Study, 1823 men aged ⩾55 years, were followed for the occurrence of depression. RMI and UMI were ascertained using electrocardiography and medical history at baseline. We determined the strength of the association of RMI and UMI with mortality, and we studied the relationship of RMI and UMI with depressive symptoms and the occurrence of major depression. The risk of mortality was similar in men with RMI [adjusted hazard ratio (aHR) 1.71, 95% confidence interval (CI) 1.45-2.03] and UMI (aHR 1.58, 95% CI 1.27-1.97). Men with RMI had on average [unstandardized regression coefficient (B) 1.14, 95% CI 0.07-2.21] higher scores for depressive symptoms. By contrast, we found no clear association between UMI and depressive symptoms (B 0.55, 95% CI -0.51 to 1.62) in men. Analysis including occurrence of major depression as the outcome were consistent with the pattern of association. The discrepant association of RMI and UMI with mortality compared to depression suggests that the psychological burden of having experienced an MI contributes to the long-term risk of depression.

  14. From The Cover: Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation

    NASA Astrophysics Data System (ADS)

    Nollen, Ellen A. A.; Garcia, Susana M.; van Haaften, Gijs; Kim, Soojin; Chavez, Alejandro; Morimoto, Richard I.; Plasterk, Ronald H. A.

    2004-04-01

    Protein misfolding and the formation of aggregates are increasingly recognized components of the pathology of human genetic disease and hallmarks of many neurodegenerative disorders. As exemplified by polyglutamine diseases, the propensity for protein misfolding is associated with the length of polyglutamine expansions and age-dependent changes in protein-folding homeostasis, suggesting a critical role for a protein homeostatic buffer. To identify the complement of protein factors that protects cells against the formation of protein aggregates, we tested transgenic Caenorhabditis elegans strains expressing polyglutamine expansion yellow fluorescent protein fusion proteins at the threshold length associated with the age-dependent appearance of protein aggregation. We used genome-wide RNA interference to identify genes that, when suppressed, resulted in the premature appearance of protein aggregates. Our screen identified 186 genes corresponding to five principal classes of polyglutamine regulators: genes involved in RNA metabolism, protein synthesis, protein folding, and protein degradation; and those involved in protein trafficking. We propose that each of these classes represents a molecular machine collectively comprising the protein homeostatic buffer that responds to the expression of damaged proteins to prevent their misfolding and aggregation. protein misfolding | neurodegenerative diseases

  15. Using an epiphytic moss to identify previously unknown sources of atmospheric cadmium pollution.

    PubMed

    Donovan, Geoffrey H; Jovan, Sarah E; Gatziolis, Demetrios; Burstyn, Igor; Michael, Yvonne L; Amacher, Michael C; Monleon, Vicente J

    2016-07-15

    Urban networks of air-quality monitors are often too widely spaced to identify sources of air pollutants, especially if they do not disperse far from emission sources. The objectives of this study were to test the use of moss bio-indicators to develop a fine-scale map of atmospherically-derived cadmium and to identify the sources of cadmium in a complex urban setting. We collected 346 samples of the moss Orthotrichum lyellii from deciduous trees in December, 2013 using a modified randomized grid-based sampling strategy across Portland, Oregon. We estimated a spatial linear model of moss cadmium levels and predicted cadmium on a 50m grid across the city. Cadmium levels in moss were positively correlated with proximity to two stained-glass manufacturers, proximity to the Oregon-Washington border, and percent industrial land in a 500m buffer, and negatively correlated with percent residential land in a 500m buffer. The maps showed very high concentrations of cadmium around the two stained-glass manufacturers, neither of which were known to environmental regulators as cadmium emitters. In addition, in response to our findings, the Oregon Department of Environmental Quality placed an instrumental monitor 120m from the larger stained-glass manufacturer in October, 2015. The monthly average atmospheric cadmium concentration was 29.4ng/m(3), which is 49 times higher than Oregon's benchmark of 0.6ng/m(3), and high enough to pose a health risk from even short-term exposure. Both stained-glass manufacturers voluntarily stopped using cadmium after the monitoring results were made public, and the monthly average cadmium levels precipitously dropped to 1.1ng/m(3) for stained-glass manufacturer #1 and 0.67ng/m(3) for stained-glass manufacturer #2. Published by Elsevier B.V.

  16. Use of court records for supplementing occupational disease surveillance.

    PubMed Central

    Schwartz, E; Landrigan, P

    1987-01-01

    To conduct surveillance of occupationally related health events, the New Hampshire Division of Public Health Services analyzes death certificates and workers' compensation claims. In an effort to bolster these limited data sources, a previously unrecognized data-set comprised of court records was explored. Court records obtained from the Federal District Court proved to be a readily accessible and detailed source of information for identifying suspected cases of asbestos-related disease and potential sources of asbestos exposure. PMID:2959164

  17. Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

    PubMed

    Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

    2016-02-01

    Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

  18. A Predictive Model Has Identified Tick-Borne Encephalitis High-Risk Areas in Regions Where No Cases Were Reported Previously, Poland, 1999–2012

    PubMed Central

    Rubikowska, Barbara; Bratkowski, Jakub; Ustrnul, Zbigniew; Vanwambeke, Sophie O.

    2018-01-01

    During 1999–2012, 77% of the cases of tick-borne encephalitis (TBE) were recorded in two out of 16 Polish provinces. However, historical data, mostly from national serosurveys, suggest that the disease could be undetected in many areas. The aim of this study was to identify which routinely-measured meteorological, environmental, and socio-economic factors are associated to TBE human risk across Poland, with a particular focus on areas reporting few cases, but where serosurveys suggest higher incidence. We fitted a zero-inflated Poisson model using data on TBE incidence recorded in 108 NUTS-5 administrative units in high-risk areas over the period 1999–2012. Subsequently we applied the best fitting model to all Polish municipalities. Keeping the remaining variables constant, the predicted rate increased with the increase of air temperature over the previous 10–20 days, precipitation over the previous 20–30 days, in forestation, forest edge density, forest road density, and unemployment. The predicted rate decreased with increasing distance from forests. The map of predicted rates was consistent with the established risk areas. It predicted, however, high rates in provinces considered TBE-free. We recommend raising awareness among physicians working in the predicted high-risk areas and considering routine use of household animal surveys for risk mapping. PMID:29617333

  19. Integron-Associated DfrB4, a Previously Uncharacterized Member of the Trimethoprim-Resistant Dihydrofolate Reductase B Family, Is a Clinically Identified Emergent Source of Antibiotic Resistance.

    PubMed

    Toulouse, Jacynthe L; Edens, Thaddeus J; Alejaldre, Lorea; Manges, Amee R; Pelletier, Joelle N

    2017-05-01

    Whole-genome sequencing of trimethoprim-resistant Escherichia coli clinical isolates identified a member of the trimethoprim-resistant type II dihydrofolate reductase gene family ( dfrB ). The dfrB4 gene was located within a class I integron flanked by multiple resistance genes. This arrangement was previously reported in a 130.6-kb multiresistance plasmid. The DfrB4 protein conferred a >2,000-fold increased trimethoprim resistance on overexpression in E. coli Our results are consistent with the finding that dfrB4 contributes to clinical trimethoprim resistance. Copyright © 2017 American Society for Microbiology.

  20. Unexpected tautomeric equilibria of the carbanion-enamine intermediate in pyruvate oxidase highlight unrecognized chemical versatility of thiamin

    PubMed Central

    Meyer, Danilo; Neumann, Piotr; Koers, Eline; Sjuts, Hanno; Lüdtke, Stefan; Sheldrick, George M.; Ficner, Ralf; Tittmann, Kai

    2012-01-01

    Thiamin diphosphate, the vitamin B1 coenzyme, plays critical roles in fundamental metabolic pathways that require acyl carbanion equivalents. Studies on chemical models and enzymes had suggested that these carbanions are resonance-stabilized as enamines. A crystal structure of this intermediate in pyruvate oxidase at 1.1 Å resolution now challenges this paradigm by revealing that the enamine does not accumulate. Instead, the intermediate samples between the ketone and the carbanion both interlocked in a tautomeric equilibrium. Formation of the keto tautomer is associated with a loss of aromaticity of the cofactor. The alternate confinement of electrons to neighboring atoms rather than π-conjugation seems to be of importance for the enzyme-catalyzed, redox-coupled acyl transfer to phosphate, which requires a dramatic inversion of polarity of the reacting substrate carbon in two subsequent catalytic steps. The ability to oscillate between a nucleophilic (carbanion) and an electrophilic (ketone) substrate center highlights a hitherto unrecognized versatility of the thiamin cofactor. It remains to be studied whether formation of the keto tautomer is a general feature of all thiamin enzymes, as it could provide for stable storage of the carbanion state, or whether this feature represents a specific trait of thiamin oxidases. In addition, the protonation state of the two-electron reduced flavin cofactor can be fully assigned, demonstrating the power of high-resolution cryocrystallography for elucidation of enzymatic mechanisms. PMID:22730460

  1. Markers for Ongoing or Previous Hepatitis E Virus Infection Are as Common in Wild Ungulates as in Humans in Sweden

    PubMed Central

    Roth, Anette; Lin, Jay; Magnius, Lars; Karlsson, Marie; Belák, Sándór; Widén, Frederik; Norder, Heléne

    2016-01-01

    Hepatitis E virus (HEV) is a human pathogen with zoonotic spread, infecting both domestic and wild animals. About 17% of the Swedish population is immune to HEV, but few cases are reported annually, indicating that most infections are subclinical. However, clinical hepatitis E may also be overlooked. For identified cases, the source of infection is mostly unknown. In order to identify whether HEV may be spread from wild game, the prevalence of markers for past and/or ongoing infection was investigated in sera and stool samples collected from 260 hunted Swedish wild ungulates. HEV markers were found in 43 (17%) of the animals. The most commonly infected animal was moose (Alces alces) with 19 out of 69 animals (28%) showing HEV markers, followed by wild boar (Sus scrofa) with 21 out of 139 animals (15%), roe deer (Capreolus capreolus) with 2 out of 30 animals, red deer (Cervus elaphus) with 1 out of 15 animals, and fallow deer (Dama dama) 0 out of 7 animals. Partial open reading frame 1 (ORF1) of the viral genomes from the animals were sequenced and compared with those from 14 endemic human cases. Phylogenetic analysis revealed that three humans were infected with HEV strains similar to those from wild boar. These results indicate that wild animals may be a source of transmission to humans and could be an unrecognized public health concern. PMID:27657108

  2. Markers for Ongoing or Previous Hepatitis E Virus Infection Are as Common in Wild Ungulates as in Humans in Sweden.

    PubMed

    Roth, Anette; Lin, Jay; Magnius, Lars; Karlsson, Marie; Belák, Sándór; Widén, Frederik; Norder, Heléne

    2016-09-19

    Hepatitis E virus (HEV) is a human pathogen with zoonotic spread, infecting both domestic and wild animals. About 17% of the Swedish population is immune to HEV, but few cases are reported annually, indicating that most infections are subclinical. However, clinical hepatitis E may also be overlooked. For identified cases, the source of infection is mostly unknown. In order to identify whether HEV may be spread from wild game, the prevalence of markers for past and/or ongoing infection was investigated in sera and stool samples collected from 260 hunted Swedish wild ungulates. HEV markers were found in 43 (17%) of the animals. The most commonly infected animal was moose ( Alces alces ) with 19 out of 69 animals (28%) showing HEV markers, followed by wild boar ( Sus scrofa ) with 21 out of 139 animals (15%), roe deer ( Capreolus capreolus ) with 2 out of 30 animals, red deer ( Cervus elaphus ) with 1 out of 15 animals, and fallow deer ( Dama dama ) 0 out of 7 animals. Partial open reading frame 1 (ORF1) of the viral genomes from the animals were sequenced and compared with those from 14 endemic human cases. Phylogenetic analysis revealed that three humans were infected with HEV strains similar to those from wild boar. These results indicate that wild animals may be a source of transmission to humans and could be an unrecognized public health concern.

  3. Homozygosity for a newly identified missense mutation in a patient with very severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID).

    PubMed Central

    Hirschhorn, R; Chakravarti, V; Puck, J; Douglas, S D

    1991-01-01

    We have identified a previously unrecognized missense mutation in a patient with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). The mutation is a G646-to-A transition at a CG dinucleotide and predicts a glycine-to-arginine substitution at codon 216. Computer analysis of secondary structure predicts a major alteration with loss of a beta-pleated sheet in a highly conserved region of the protein. The basepair substitution also generates a new site for the restriction enzyme BstXI in exon 7 of the genomic DNA. Digestion of genomic DNA from the patient and from his parents revealed that he was homozygous for the mutation and that his mother and father were carriers. This mutation in homozygous form appears to be associated with very severe disease, since the patient had perinatal onset of clinical manifestations of SCID, the highest concentration of the toxic metabolite deoxyATP in nine patients studied, and a relatively poor immunologic response during the initial 2 years of therapy with polyethylene glycol-adenosine deaminase. Analysis of DNA from 21 additional patients with ADA-SCID and from 19 unrelated normals revealed that, while none of the normal individuals showed the abnormal restriction fragment, two of the 21 patients studied were heterozygous for the G646-to-A mutation. Images Figure 2 PMID:1680289

  4. CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

    PubMed

    Taghizadeh, Rouzbeh; Noh, Minsoo; Huh, Yang Hoon; Ciusani, Emilio; Sigalotti, Luca; Maio, Michele; Arosio, Beatrice; Nicotra, Maria R; Natali, PierGiorgio; Sherley, James L; La Porta, Caterina A M

    2010-12-22

    A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone. The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

  5. Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes.

    PubMed

    Auvergne, Romane M; Sim, Fraser J; Wang, Su; Chandler-Militello, Devin; Burch, Jaclyn; Al Fanek, Yazan; Davis, Danielle; Benraiss, Abdellatif; Walter, Kevin; Achanta, Pragathi; Johnson, Mahlon; Quinones-Hinojosa, Alfredo; Natesan, Sridaran; Ford, Heide L; Goldman, Steven A

    2013-06-27

    Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5+ glioma tumor progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs in vitro and in vivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Constraints on formation processes of two coarse-grained calcium- aluminum-rich inclusions: a study of mantles, islands and cores

    USGS Publications Warehouse

    Meeker, G.P.

    1995-01-01

    Many coarse-grained calcium- aluminum-rich inclusions (CAIs) contain features that are inconsistent with equilibrium liquid crystallization models of origin. Spinel-free islands (SFIs) in spinel-rich cores of Type B CAIs are examples of such features. One model previously proposed for the origin of Allende 5241, a Type B1 CAI containing SFIs, involves the capture and assimilation of xenoliths by a liquid droplet in the solar nebula (El Goresy et al, 1985; MacPherson et al 1989). This study reports new textural and chemical zoning data from 5241 and identifies previously unrecognized chemical zoning patterns in the melilite mantle and in a SFI. -from Author

  7. Identification of mineral resources in Afghanistan-Detecting and mapping resource anomalies in prioritized areas using geophysical and remote sensing (ASTER and HyMap) data

    USGS Publications Warehouse

    King, Trude V.V.; Johnson, Michaela R.; Hubbard, Bernard E.; Drenth, Benjamin J.

    2011-01-01

    During the independent analysis of the geophysical, ASTER, and imaging spectrometer (HyMap) data by USGS scientists, previously unrecognized targets of potential mineralization were identified using evaluation criteria most suitable to the individual dataset. These anomalous zones offer targets of opportunity that warrant additional field verification. This report describes the standards used to define the anomalies, summarizes the results of the evaluations for each type of data, and discusses the importance and implications of regions of anomaly overlap between two or three of the datasets.

  8. Use of dust storm observations on satellite images to identify areas vulnerable to severe wind erosion

    USGS Publications Warehouse

    Breed, C.S.; McCauley, J.F.

    1986-01-01

    Blowing dust is symptomatic of severe wind erosion and deterioration of soils in areas undergoing dessication and/or devegetation. Dust plumes on satellite images can commonly be traced to sources in marginally arable semiarid areas where protective lag gravels or vegetation have been removed and soils are dry, as demonstrated for the Portales Valley, New Mexico. Images from Landsat and manned orbiters such as Skylab and the Space Shuttle are useful for illustrating the regional relations of airborne dust plumes to source areas. Geostationary satellites such as GOES are useful in tracking the time-histories of episodic dust storms. These events sometimes go unrecognized by weather observers and are the precursors of long-term land degradation trends. In areas where soil maps and meteorological data are inadequate, satellite images provide a means for identifying problem areas where measures are needed to control or mitigate wind erosion. ?? 1986 D. Reidel Publishing Company.

  9. Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.

    PubMed

    Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

    2015-01-01

    Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability--the basis of cluster generation--is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.

  10. Identifying and Assessing Interesting Subgroups in a Heterogeneous Population

    PubMed Central

    Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

    2015-01-01

    Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability—the basis of cluster generation—is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided. PMID:26339613

  11. Cocoon formation in patients with midgut neuroendocrine tumors: a rare and unrecognized final pathway.

    PubMed

    Wang, Yi-Zarn; King, Heather; Diebold, Anne

    2013-08-01

    Neuroendocrine tumors (NETs) are relatively rare with an indolent nature. As a result, treatment is often delayed and passive. The most commonly recognized disease progression leading to death is from the sequelae of bowel obstruction, ischemia, or liver failure secondary to liver metastasis. We recently recognized a rare cocoon-like formation in patients with metastatic gastroenteropancreatic NETs and hypothesize that this may be a distinct, final pathway for these patients. Ten patients with stage IV gastroenteropancreatic NETs, seen at our center between October 2008 and November 2011, who developed a cocoon were identified. Patient's charts, operative reports, pathology, and tumor markers were reviewed. No discernable predictors were identified as precursors to this condition. One patient survived 13 months after cocoon diagnosis, and the remaining 9 patients were all deceased within 5 months. Surgical treatment was attempted in 6 patients and was only partially successful in 1 patient who had the earliest stage of cocoon formation (type 1). Cocoon-like formations in patients with stage IV gastroenteropancreatic NETs is rare and may be a terminal disease progression that has not been previously recognized. The best treatment option remains unknown. Surgical treatment is not advisable, with the exception of type 1 abdominal cocoons.

  12. Mutations in the Gene Encoding IFT Dynein Complex Component WDR34 Cause Jeune Asphyxiating Thoracic Dystrophy

    PubMed Central

    Schmidts, Miriam; Vodopiutz, Julia; Christou-Savina, Sonia; Cortés, Claudio R.; McInerney-Leo, Aideen M.; Emes, Richard D.; Arts, Heleen H.; Tüysüz, Beyhan; D’Silva, Jason; Leo, Paul J.; Giles, Tom C.; Oud, Machteld M.; Harris, Jessica A.; Koopmans, Marije; Marshall, Mhairi; Elçioglu, Nursel; Kuechler, Alma; Bockenhauer, Detlef; Moore, Anthony T.; Wilson, Louise C.; Janecke, Andreas R.; Hurles, Matthew E.; Emmet, Warren; Gardiner, Brooke; Streubel, Berthold; Dopita, Belinda; Zankl, Andreas; Kayserili, Hülya; Scambler, Peter J.; Brown, Matthew A.; Beales, Philip L.; Wicking, Carol; Duncan, Emma L.; Mitchison, Hannah M.

    2013-01-01

    Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery. PMID:24183451

  13. Computational and transcriptional evidence for microRNAs in the honey bee genome

    PubMed Central

    Weaver, Daniel B; Anzola, Juan M; Evans, Jay D; Reid, Jeffrey G; Reese, Justin T; Childs, Kevin L; Zdobnov, Evgeny M; Samanta, Manoj P; Miller, Jonathan; Elsik, Christine G

    2007-01-01

    Background Non-coding microRNAs (miRNAs) are key regulators of gene expression in eukaryotes. Insect miRNAs help regulate the levels of proteins involved with development, metabolism, and other life history traits. The recently sequenced honey bee genome provides an opportunity to detect novel miRNAs in both this species and others, and to begin to infer the roles of miRNAs in honey bee development. Results Three independent computational surveys of the assembled honey bee genome identified a total of 65 non-redundant candidate miRNAs, several of which appear to have previously unrecognized orthologs in the Drosophila genome. A subset of these candidate miRNAs were screened for expression by quantitative RT-PCR and/or genome tiling arrays and most predicted miRNAs were confirmed as being expressed in at least one honey bee tissue. Interestingly, the transcript abundance for several known and novel miRNAs displayed caste or age-related differences in honey bees. Genes in proximity to miRNAs in the bee genome are disproportionately associated with the Gene Ontology terms 'physiological process', 'nucleus' and 'response to stress'. Conclusion Computational approaches successfully identified miRNAs in the honey bee and indicated previously unrecognized miRNAs in the well-studied Drosophila melanogaster genome despite the 280 million year distance between these insects. Differentially transcribed miRNAs are likely to be involved in regulating honey bee development, and arguably in the extreme developmental switch between sterile worker bees and highly fertile queens. PMID:17543122

  14. Interpretation of the Last Chance thrust, Death Valley region, California, as an Early Permian décollement in a previously undeformed shale basin

    USGS Publications Warehouse

    Stevens, Calvin H.; Stone, Paul

    2005-01-01

    We interpret the Last Chance thrust as similar in many ways to Appalachian-type décollements in which the zone of thrusting is localized along a shale interval. The Last Chance thrust, however, has been dismembered during later geologic events so that its original geometry has been obscured. Our model may have unrecognized analogs in other structurally complex shale basins in which the initial deformation was along a major shale unit.

  15. The number of unrecognized myocardial infarction scars detected at DE-MRI increases during a 5-year follow-up.

    PubMed

    Themudo, Raquel; Johansson, Lars; Ebeling-Barbier, Charlotte; Lind, Lars; Ahlström, Håkan; Bjerner, Tomas

    2017-02-01

    In an elderly population, the prevalence of unrecognized myocardial infarction (UMI) scars found via late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging was more frequent than expected. This study investigated whether UMI scars detected with LGE-CMR at age 70 would be detectable at age 75 and whether the scar size changed over time. From 248 participants that underwent LGE-CMR at age 70, 185 subjects underwent a follow-up scan at age 75. A myocardial infarction (MI) scar was defined as late enhancement involving the subendocardium. In the 185 subjects that underwent follow-up, 42 subjects had a UMI scar at age 70 and 61 subjects had a UMI scar at age 75. Thirty-seven (88 %) of the 42 UMI scars seen at age 70 were seen in the same myocardial segment at age 75. The size of UMI scars did not differ between age 70 and 75. The prevalence of UMI scars detected at LGE-CMR increases with age. During a 5-year follow-up, 88 % (37/42) of the UMI scars were visible in the same myocardial segment, reassuring that UMI scars are a consistent finding. The size of UMI scars detected during LGE-CMR did not change over time. • UMI scars detected by LGE-CMR are frequent in elderly. • The prevalence of UMI scars detected with LGE-CMR increases with age. • UMI scar size does not change over time.

  16. Transcriptomic Analysis in a Drosophila Model Identifies Previously Implicated and Novel Pathways in the Therapeutic Mechanism in Neuropsychiatric Disorders

    PubMed Central

    Singh, Priyanka; Mohammad, Farhan; Sharma, Abhay

    2011-01-01

    We have taken advantage of a newly described Drosophila model to gain insights into the potential mechanism of antiepileptic drugs (AEDs), a group of drugs that are widely used in the treatment of several neurological and psychiatric conditions besides epilepsy. In the recently described Drosophila model that is inspired by pentylenetetrazole (PTZ) induced kindling epileptogenesis in rodents, chronic PTZ treatment for 7 days causes a decreased climbing speed and an altered CNS transcriptome, with the latter mimicking gene expression alterations reported in epileptogenesis. In the model, an increased climbing speed is further observed 7 days after withdrawal from chronic PTZ. We used this post-PTZ withdrawal regime to identify potential AED mechanism. In this regime, treatment with each of the five AEDs tested, namely, ethosuximide, gabapentin, vigabatrin, sodium valproate, and levetiracetam, resulted in rescuing of the altered climbing behavior. The AEDs also normalized PTZ withdrawal induced transcriptomic perturbation in fly heads; whereas AED untreated flies showed a large number of up- and down-regulated genes which were enriched in several processes including gene expression and cell communication, the AED treated flies showed differential expression of only a small number of genes that did not enrich gene expression and cell communication processes. Gene expression and cell communication related upregulated genes in AED untreated flies overrepresented several pathways – spliceosome, RNA degradation, and ribosome in the former category, and inositol phosphate metabolism, phosphatidylinositol signaling, endocytosis, and hedgehog signaling in the latter. Transcriptome remodeling effect of AEDs was overall confirmed by microarray clustering that clearly separated the profiles of AED treated and untreated flies. Besides being consistent with previously implicated pathways, our results provide evidence for a role of other pathways in psychiatric drug

  17. 36 CFR 60.14 - Changes and revisions to properties listed in the National Register.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... exist for altering a boundary: Professional error in the initial nomination, loss of historic integrity... previously unrecognized significance in American history, architecture, archeology, engineering or culture...

  18. UNRECOGNIZED OR POTENTIAL RISK FACTORS FOR CHILDHOOD CANCER

    EPA Science Inventory

    Traditional epidemiological studies suggest that the contribution of environmental agents to childhood cancer may be minor. However, epidemiological methods can only seldom identify causal factors associated with a relative risk of less than a factor of one and a half to two. App...

  19. A new commelinid monocot seed fossil from the early Eocene previously identified as Solanaceae.

    PubMed

    Särkinen, Tiina; Kottner, Sören; Stuppy, Wolfgang; Ahmed, Farah; Knapp, Sandra

    2018-01-01

    Fossils provide minimum age estimates for extant lineages. Here we critically evaluate Cantisolanum daturoides Reid & Chandler and two other early putative seed fossils of Solanaceae, an economically important plant family in the Asteridae. Three earliest seed fossil taxa of Solanaceae from the London Clay Formation (Cantisolanum daturoides) and the Poole and Branksome Sand Formations (Solanum arnense Chandler and Solanispermum reniforme Chandler) were studied using x-ray microcomputed tomography (MCT) and scanning electron microscopy (SEM). The MCT scans of Cantisolanum daturoides revealed a high level of pyrite preservation at the cellular level. Cantisolanum daturoides can be clearly excluded from Solanaceae and has more affinities to the commelinid monocots based on a straight longitudinal axis, a prominent single layer of relatively thin-walled cells in the testa, and a clearly differentiated micropyle surrounded by radially elongated and inwardly curved testal cells. While the MCT scans show no internal preservation in Solanum arnense and Solanispermum reniforme, SEM images show the presence of several characteristics that allow the placement of these taxa at the stem node of Solanaceae. Cantisolanum daturoides is likely a member of commelinid monocots and not Solanaceae as previously suggested. The earliest fossil record of Solanaceae is revised to consist of fruit fossil with inflated calyces from the early Eocene of Patagonia (52 Ma) and fossilized seeds from the early to mid-Eocene of Europe (48-46 Ma). The new identity for Cantisolanum daturoides does not alter a late Cretaceous minimum age for commelinids. © 2018 Botanical Society of America.

  20. NIH Researchers Identify OCD Risk Gene

    MedlinePlus

    ... News From NIH NIH Researchers Identify OCD Risk Gene Past Issues / Summer 2006 Table of Contents For ... and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual's risk for obsessive- ...

  1. Improving the Inventory of Large Lunar Basins: Using LOLA Data to Test Previous Candidates and Search for New Ones

    NASA Technical Reports Server (NTRS)

    Frey, H. V.; Meyer, H. M.; Romine, G. C.

    2012-01-01

    Topography and crustal thickness data from LOLA altimetry were used to test the validity of 98 candidate large lunar basins derived from photogeologic and earlier topographic and crustal thickness data, and to search for possible new candidates. We eliminate 23 previous candidates but find good evidence for 20 new candidates. The number of basins greater than 300 km diameter on the Moon is almost certainly a factor 2 (maybe 3?) larger than the number of named features having basin-like topography. Unified Lunar Control Net 2005 data [1] and model crustal thickness data [2] were previously used to search for possible previously unrecognized large lunar impact basins [3,4]. An inventory of 98 candidate topographic basins greater than 300 km in diameter was found [5]. This includes 33 named features (only those having basin-like topography) out of the 45 listed by Wilhelms [6], 38 additional Quasi-Circular Depressions (QCDs) found in the ULCN2005 topography, and 27 Circular Thin Areas (CTAs) found in model crustal thickness data [2]. Most named features and additional QCDs have strong CTA signatures, but there may be a class of CTAs that are not easily recognized in the old and low resolution ULCN2005 topography. Lunar Orbiter Laser Altimeter (LOLA) data have recently become publically available. We used these data to (a) refine the center and ring diameters of known basins, (b) test the viability of the candidate basins previously found (as described above), and (c) search for additional candidate basins not revealed by the earlier lower resolution data. We used the LOLA topography directly but also a recent new model crustal thickness data that includes Kaguya gravity data [7]. We repeated a Topographic Expression (TE) and a Crustal Thickness Expression (CTE) scoring exercise originally done with the basins found in ULCN and earlier model crustal thickness data [5]. Each candidate was scored on a scale from 0 (no topographic basin or circular thin area signature) to

  2. Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation

    PubMed Central

    Badal, Brateil; Solovyov, Alexander; Di Cecilia, Serena; Chan, Joseph Minhow; Chang, Li-Wei; Iqbal, Ramiz; Aydin, Iraz T.; Rajan, Geena S.; Chen, Chen; Abbate, Franco; Arora, Kshitij S.; Tanne, Antoine; Gruber, Stephen B.; Johnson, Timothy M.; Fullen, Douglas R.; Phelps, Robert; Bhardwaj, Nina; Bernstein, Emily; Ting, David T.; Brunner, Georg; Schadt, Eric E.; Greenbaum, Benjamin D.; Celebi, Julide Tok

    2017-01-01

    BACKGROUND. Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS. We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts. RESULTS. Gene expression changes unequivocally discriminated between benign and malignant states, and a dual epigenetic and immune signature emerged defining this transition. To our knowledge, we discovered previously unrecognized melanoma subtypes. A high-risk primary melanoma subset was distinguished by a 122-epigenetic gene signature (“epigenetic” cluster) and TP53 family gene deregulation (TP53, TP63, and TP73). This subtype associated with poor overall survival and showed enrichment of cell cycle genes. Noncoding repetitive element transcripts (LINEs, SINEs, and ERVs) that can result in immunostimulatory signals recapitulating a state of “viral mimicry” were significantly repressed. The high-risk subtype and its poor predictive characteristics were validated in several independent cohorts. Additionally, primary melanomas distinguished by specific immune signatures (“immune” clusters) were identified. CONCLUSION. The TP53 family of genes and genes regulating the epigenetic machinery demonstrate strong prognostic and biological relevance during progression of early disease. Gene expression profiling of protein-coding and -noncoding RNA transcripts may be a better predictor for disease course in melanoma. This study outlines the transcriptional interplay of the cancer cell’s epigenome with the immune milieu with potential for future therapeutic targeting. FUNDING

  3. Loss of Autonoetic Awareness of Recent Autobiographical Episodes and Accelerated Long-Term Forgetting in a Patient with Previously Unrecognized Glutamic Acid Decarboxylase Antibody Related Limbic Encephalitis.

    PubMed

    Witt, Juri-Alexander; Vogt, Viola Lara; Widman, Guido; Langen, Karl-Josef; Elger, Christian Erich; Helmstaedter, Christoph

    2015-01-01

    We describe a 35-year-old male patient presenting with depressed mood and emotional instability, who complained about severe anterograde and retrograde memory deficits characterized by accelerated long-term forgetting and loss of autonoetic awareness regarding autobiographical memories of the last 3 years. Months before he had experienced two breakdowns of unknown etiology giving rise to the differential diagnosis of epileptic seizures after various practitioners and clinics had suggested different etiologies such as a psychosomatic condition, burnout, depression, or dissociative amnesia. Neuropsychological assessment indicated selectively impaired figural memory performance. Extended diagnostics confirmed accelerated forgetting of previously learned and retrievable verbal material. Structural imaging showed bilateral swelling and signal alterations of temporomesial structures (left >right). Video-EEG monitoring revealed a left temporal epileptic focus and subclincal seizure, but no overt seizures. Antibody tests in serum and liquor were positive for glutamic acid decarboxylase antibodies. These findings led to the diagnosis of glutamic acid decarboxylase antibody related limbic encephalitis. Monthly steroid pulses over 6 months led to recovery of subjective memory and to intermediate improvement but subsequent worsening of objective memory performance. During the course of treatment, the patient reported de novo paroxysmal non-responsive states. Thus, antiepileptic treatment was started and the patient finally became seizure free. At the last visit, vocational reintegration was successfully in progress. In conclusion, amygdala swelling, retrograde biographic memory impairment, accelerated long-term forgetting, and emotional instability may serve as indicators of limbic encephalitis, even in the absence of overt epileptic seizures. The monitoring of such patients calls for a standardized and concerted multilevel diagnostic approach with repeated assessments.

  4. Investigating the effect of previous treatments on wheat biomass over multiple spatial frequencies

    NASA Astrophysics Data System (ADS)

    Milne, A. E.; Castellanos, M. T.; Cartagena, M. C.; Tarquis, A. M.; Lark, R. M.

    2010-09-01

    In this study we use the maximum overlap discrete packet transform (MODWPT) to investigate residual effects on wheat biomass of fertigation treatments applied to a previous crop. The wheat crop covered nine subplots from a previous experiment on melon response to fertigation. Each subplot had previously received a different level of applied nitrogen. Many factors affect wheat biomass, causing it to vary at different spatial frequencies. We hypothesize that these will include residual effects from fertilizer application (at relatively low spatial frequencies) and the local influence of individual plants from the previous melon crop (at high frequency). To test this hypothesis we use the MODWPT to identify the dominant spatial frequencies of wheat biomass variation, and analyse the relationship to both the previous fertilizer application and the location of individual melon plants in the previous crop. The MODWPT is particularly appropriate for this because it allows us first to identify the key spatial frequencies in the wheat biomass objectively and to analyse them, and their relationship to hypothesized driving factors without any assumptions of uniformity (stationarity) of wheat-biomass variation. The results showed that the applied nitrogen dominated the wheat biomass response, and that there was a noticeable component of wheat-biomass variation at the spatial frequency that corresponds to the melon cropping. We expected wheat biomass to be negatively correlated with the position of melons in the previous crop, due to uptake of the applied nitrogen. The MODWPT, which allows us to detect changes in correlation between variables at different frequencies, showed that such a relationship was found across part of the experiment but not uniformly.

  5. Special article: Horace Nelson MD, John Webster LDS--unrecognized Canadian anesthesia pioneers.

    PubMed

    Craig, Douglas; Chartrand, Daniel

    2014-03-01

    The timing of the earliest reported ether anesthetics in early 1847, in regions to become Canada in July 1867, was examined using information from on-line and library-based sources. Previous authors had identified the first reported ether anesthetic given by a visiting American dentist in January 1847 in Saint John, New Brunswick. Nevertheless, they had reported three different anesthetics as the second occurrence - which would denote the first anesthetic given by a resident of Canada. We confirmed that there were no reports of ether anesthetics being given in Canada before that reported on January 18, 1847 in Saint John. The information available for our review indicates that the second ether anesthetic, and the first by a Canadian, was given in Montreal by a dentist, Dr. John Horatio Webster, on February 20, 1847. The surgical assistant for that operation, Dr. Horace Nelson, later reported on animal and human experiments with ether, which he had led in Montreal starting in January 1847. Earlier authors, who may not have had access to the information now available, came to incorrect conclusions about the first ether anesthetic reported to have been given by a Canadian. Current information indicates that John Webster gave the first reported anesthetic in Montreal on February 20, 1847 following experiments with ether led by Horace Nelson. Both Webster and Nelson deserve recognition as Canadian anesthesia pioneers.

  6. Chloroplast phylogenomic analysis of chlorophyte green algae identifies a novel lineage sister to the Sphaeropleales (Chlorophyceae).

    PubMed

    Lemieux, Claude; Vincent, Antony T; Labarre, Aurélie; Otis, Christian; Turmel, Monique

    2015-12-01

    The class Chlorophyceae (Chlorophyta) includes morphologically and ecologically diverse green algae. Most of the documented species belong to the clade formed by the Chlamydomonadales (also called Volvocales) and Sphaeropleales. Although studies based on the nuclear 18S rRNA gene or a few combined genes have shed light on the diversity and phylogenetic structure of the Chlamydomonadales, the positions of many of the monophyletic groups identified remain uncertain. Here, we used a chloroplast phylogenomic approach to delineate the relationships among these lineages. To generate the analyzed amino acid and nucleotide data sets, we sequenced the chloroplast DNAs (cpDNAs) of 24 chlorophycean taxa; these included representatives from 16 of the 21 primary clades previously recognized in the Chlamydomonadales, two taxa from a coccoid lineage (Jenufa) that was suspected to be sister to the Golenkiniaceae, and two sphaeroplealeans. Using Bayesian and/or maximum likelihood inference methods, we analyzed an amino acid data set that was assembled from 69 cpDNA-encoded proteins of 73 core chlorophyte (including 33 chlorophyceans), as well as two nucleotide data sets that were generated from the 69 genes coding for these proteins and 29 RNA-coding genes. The protein and gene phylogenies were congruent and robustly resolved the branching order of most of the investigated lineages. Within the Chlamydomonadales, 22 taxa formed an assemblage of five major clades/lineages. The earliest-diverging clade displayed Hafniomonas laevis and the Crucicarteria, and was followed by the Radicarteria and then by the Chloromonadinia. The latter lineage was sister to two superclades, one consisting of the Oogamochlamydinia and Reinhardtinia and the other of the Caudivolvoxa and Xenovolvoxa. To our surprise, the Jenufa species and the two spine-bearing green algae belonging to the Golenkinia and Treubaria genera were recovered in a highly supported monophyletic group that also included three taxa

  7. Previous history of tuberculosis is associated with rheumatoid arthritis.

    PubMed

    Shen, T-C; Lin, C-L; Wei, C-C; Chen, C-H; Tu, C-Y; Hsia, T-C; Shih, C-M; Hsu, W-H; Chung, C-J; Sung, F-C; Kao, C-H

    2015-11-01

    Previous studies have suggested that mycobacterial infections could trigger autoimmune diseases, including rheumatoid arthritis (RA). To explore the association between previous tuberculosis (TB) and RA. We conducted a case-control study using data obtained from the National Health Insurance (NHI) system of Taiwan. We identified 26 535 adults with RA from 2002 to 2011, with the date of diagnosis as the index date. This number was randomly selected and frequency-matched four times by age, sex and the year of index date from among non-RA individuals. Odds ratios (ORs) of RA were calculated for associations with TB. Compared with controls, RA patients had a crude OR of 1.77 for TB (95%CI 1.61-1.94). The strength of the association between RA and TB remained at the same level after controlling for other potential risk factors (adjusted OR 1.73, 95%CI 1.57-1.90), although RA patients tended to have a higher prevalence of hypertension, coronary artery disease and kidney disease. TB was much more prevalent in RA patients than in control subjects. Prospective cohort studies are required to establish a causal relationship between previous TB and RA.

  8. LAPAROSCOPY AFTER PREVIOUS LAPAROTOMY

    PubMed Central

    Godinjak, Zulfo; Idrizbegović, Edin; Begić, Kerim

    2006-01-01

    Following the abdominal surgery, extensive adhesions often occur and they can cause difficulties during laparoscopic operations. However, previous laparotomy is not considered to be a contraindication for lap-aroscopy. The aim of this study is to present that an insertion of Veres needle in the region of umbilicus is a safe method for creating a pneumoperitoneum for laparoscopic operations after previous laparotomy. In the last three years, we have performed 144 laparoscopic operations in patients that previously underwent one or two laparotomies. Pathology of digestive system, genital organs, Cesarean Section or abdominal war injuries were the most common causes of previous laparotomy. During those operations or during entering into abdominal cavity we have not experienced any complications, while in 7 patients we performed conversion to laparotomy following the diagnostic laparoscopy. In all patients an insertion of Veres needle and trocar insertion in the umbilical region was performed, namely a technique of closed laparoscopy. Not even in one patient adhesions in the region of umbilicus were found, and no abdominal organs were injured. PMID:17177649

  9. [Antimicrobial resistance testing in clinical practice].

    PubMed

    Doi, Yohei

    2012-02-01

    Previously unrecognized or underrecognized antimicrobial resistant bacteria, including NDM-1-producing Enterobacteriaceae and multidrug-resistant Acinetobacter baumannii, were recently identified in health care facilities in Japan. Vigilance in the clinical microbiology laboratory for these organisms is the key to early recognition of their emergence. Many of these organisms can be confirmed or at least suspected through routine susceptibility testing, which can then be referred to reference laboratories for further phenotypic or genetic testing. Antimicrobial resistance testing plays a crucial role in patient management, infection control and monitoring of local as well as national and international epidemiology.

  10. Evaluation of radiometric and geometric characteristics of LANDSAT-D imaging system

    NASA Technical Reports Server (NTRS)

    Salisbury, J. W.; Podwysocki, M. H.; Bender, L. U.; Rowan, L. C. (Principal Investigator)

    1983-01-01

    With vegetation masked and noise sources eliminated or minimized, different carbonate facies could be discriminated in a south Florida scene. Laboratory spectra of grab samples indicate that a 20% change in depth of the carbonate absorption band was detected despite the effects of atmospheric absorption. Both bright and dark hydrothermally altered volcanic rocks can be discriminated from their unaltered equivalents. A previously unrecognized altered area was identified on the basis of the TM images. The ability to map desert varnish in semi-arid terrains has economic significance as it defines areas that are less susceptible desert erosional process and suitable for construction development.

  11. Seafloor character and sedimentary processes in eastern Long Island Sound and western Block Island Sound

    USGS Publications Warehouse

    Poppe, Lawrence J.; Cohen-DiGiacomo, M. L.; Smith, S.M.; Stewart, H.F.; Forfinski, N.A.

    2006-01-01

    Multibeam bathymetric data and seismic-reflection profiles collected in eastern Long Island Sound and western Block Island Sound reveal previously unrecognized glacial features and modern bedforms. Glacial features include an ice-sculptured bedrock surface, a newly identified recessional moraine, exposed glaciolacustrine sediments, and remnants of stagnant-ice-contact deposits. Modern bedforms include fields of transverse sand waves, barchanoid waves, giant scour depressions, and pockmarks. Bedform asymmetry and scour around obstructions indicate that net sediment transport is westward across the northern part of the study area near Fishers Island, and eastward across the southern part near Great Gull Island.

  12. Robot-assisted laparoscopic prostatectomy and previous surgical history: a multidisciplinary approach.

    PubMed

    Bernstein, Adrien N; Lavery, Hugh J; Hobbs, Adele R; Chin, Edward; Samadi, David B

    2013-06-01

    Previous abdominal or prostate surgery can be a significant barrier to subsequent minimally invasive procedures, including radical prostatectomy (RP). This is relevant to a quarter of prostatectomy patients who have had previous surgery. The technological advances of robot-assisted laparoscopic RP (RALP) can mitigate some of these challenges. To that end, our objective was to elucidate the effect of previous surgery on RALP, and to describe a multidisciplinary approach to the previously entered abdomen. One-thousand four-hundred and fourteen RALP patients were identified from a single-surgeon database. Potentially difficult cases were discussed preoperatively and treated in a multidisciplinary fashion with a general surgeon. Operative, pathological, and functional outcomes were analyzed after stratification by previous surgical history. Four-hundred and twenty (30 %) patients underwent previous surgery at least once. Perioperative outcomes were similar among most groups. Previous major abdominal surgery was associated with increased operative time (147 vs. 119 min, p < 0.001), as was the presence of adhesions (120 vs. 154 min, p < 0.001). Incidence of complications was comparable, irrespective of surgical history. Major complications included two enterotomies diagnosed intraoperatively and one patient requiring reoperation. All cases were performed robotically, without conversion to open-RP. There was no difference in biochemical disease-free survival among surgical groups and continence and potency were equivalent between groups. In conclusion, previous abdominal surgery did not affect the safety or feasibility of RALP, with all patients experiencing comparable perioperative, functional, and oncologic outcomes.

  13. Previously unknown species of Aspergillus.

    PubMed

    Gautier, M; Normand, A-C; Ranque, S

    2016-08-01

    The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care. Copyright © 2016 European Society of Clinical Microbiology and

  14. Characterization of previously unidentified lunar pyroclastic deposits using Lunar Reconnaissance Orbiter Camera (LROC) data

    USGS Publications Warehouse

    Gustafson, J. Olaf; Bell, James F.; Gaddis, Lisa R.R.; Hawke, B. Ray Ray; Giguere, Thomas A.

    2012-01-01

    We used a Lunar Reconnaissance Orbiter Camera (LROC) global monochrome Wide-angle Camera (WAC) mosaic to conduct a survey of the Moon to search for previously unidentified pyroclastic deposits. Promising locations were examined in detail using LROC multispectral WAC mosaics, high-resolution LROC Narrow Angle Camera (NAC) images, and Clementine multispectral (ultraviolet-visible or UVVIS) data. Out of 47 potential deposits chosen for closer examination, 12 were selected as probable newly identified pyroclastic deposits. Potential pyroclastic deposits were generally found in settings similar to previously identified deposits, including areas within or near mare deposits adjacent to highlands, within floor-fractured craters, and along fissures in mare deposits. However, a significant new finding is the discovery of localized pyroclastic deposits within floor-fractured craters Anderson E and F on the lunar farside, isolated from other known similar deposits. Our search confirms that most major regional and localized low-albedo pyroclastic deposits have been identified on the Moon down to ~100 m/pix resolution, and that additional newly identified deposits are likely to be either isolated small deposits or additional portions of discontinuous, patchy deposits.

  15. Prevention of unrecognized joint penetration during internal fixation of hip fractures: a geometric model based on Steinmetz Solid.

    PubMed

    Mao, Yujiang; Song, Jie; Wei, Jie; Wang, Manyi

    2010-01-01

    Unrecognized joint penetration (UJP) by screw penetration through the articular surface undetectable on routine anteroposterior (AP) and lateral radiographs can cause serious complications. We have developed a geometric model to analyze UJP, and methods for the prevention of the problem. A Steinmetz Solid (SS) is the overlapping portion between two identical, vertically intersecting cylinders. The AP and lateral radiographs of a femoral head (simplified as a sphere) are projections of two cylinder-shaped images. A screw that appears to be within the femoral head in fact only lies within the cylinder. A screw apparently within the femoral head on both AP and lateral images is only confined to the SS generated by two cylinders, but not necessarily confined to the femoral head itself. We have therefore analyzed UJP using a geometric model based on SS. The geometric basis of UJP lies in the fact that the SS is larger than the sphere (femoral head) with a volume ratio of 4: π. The theoretical risk of UJP for any screw therefore can be as high as 21.5% ((4-π)/4). In reality, screws are always carefully placed to ensure a distance between the screw's tip and the edge of femoral head (tip-to-edge distance, or TED). This TED effectively lowers the risk of UJP by reducing the size of the screw-confining SS. When the SS entirely fits into (internally tangential to) the femoral head, the risk of UJP approaches zero. A TED fulfilling this requirement can be regarded as safe (approximately 0.29 x femoral head radius). With a femoral head diameter of 5 cm, the safe TED is approximately 7 mm.

  16. Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

    PubMed Central

    Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

    2010-01-01

    Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

  17. Hidden weapons of microbial destruction in plant genomes

    PubMed Central

    Manners, John M

    2007-01-01

    Recent bioinformatic analyses of sequenced plant genomes reveal a previously unrecognized abundance of genes encoding antimicrobial cysteine-rich peptides, representing a formidable and dynamic defense arsenal against plant pests and pathogens. PMID:17903311

  18. The Unrecognized Crisis: Library Reference Service at the Crossroads.

    ERIC Educational Resources Information Center

    Hernon, Peter

    1986-01-01

    Briefly describes fundamental problems with library reference service based on the findings of 20 separate studies using unobtrusive tests. An emphasis on quality of service, realistic goals, and effective managerial strategies are identified as possible resolutions of these problems. (CLB)

  19. Visualizing in situ translational activity for identifying and sorting slow-growing archaeal−bacterial consortia

    PubMed Central

    Hatzenpichler, Roland; Connon, Stephanie A.; Goudeau, Danielle; Malmstrom, Rex R.; Woyke, Tanja; Orphan, Victoria J.

    2016-01-01

    To understand the biogeochemical roles of microorganisms in the environment, it is important to determine when and under which conditions they are metabolically active. Bioorthogonal noncanonical amino acid tagging (BONCAT) can reveal active cells by tracking the incorporation of synthetic amino acids into newly synthesized proteins. The phylogenetic identity of translationally active cells can be determined by combining BONCAT with rRNA-targeted fluorescence in situ hybridization (BONCAT-FISH). In theory, BONCAT-labeled cells could be isolated with fluorescence-activated cell sorting (BONCAT-FACS) for subsequent genetic analyses. Here, in the first application, to our knowledge, of BONCAT-FISH and BONCAT-FACS within an environmental context, we probe the translational activity of microbial consortia catalyzing the anaerobic oxidation of methane (AOM), a dominant sink of methane in the ocean. These consortia, which typically are composed of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria, have been difficult to study due to their slow in situ growth rates, and fundamental questions remain about their ecology and diversity of interactions occurring between ANME and associated partners. Our activity-correlated analyses of >16,400 microbial aggregates provide the first evidence, to our knowledge, that AOM consortia affiliated with all five major ANME clades are concurrently active under controlled conditions. Surprisingly, sorting of individual BONCAT-labeled consortia followed by whole-genome amplification and 16S rRNA gene sequencing revealed previously unrecognized interactions of ANME with members of the poorly understood phylum Verrucomicrobia. This finding, together with our observation that ANME-associated Verrucomicrobia are found in a variety of geographically distinct methane seep environments, suggests a broader range of symbiotic relationships within AOM consortia than previously thought. PMID:27357680

  20. Visualizing in situ translational activity for identifying and sorting slow-growing archaeal-bacterial consortia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hatzenpichler, Roland; Connon, Stephanie A.; Goudeau, Danielle

    To understand the biogeochemical roles of microorganisms in the environment, it is important to determine when and under which conditions they are metabolically active. Bioorthogonal noncanonical amino acid tagging (BONCAT) can reveal active cells by tracking the incorporation of synthetic amino acids into newly synthesized proteins. The phylogenetic identity of translationally active cells can be determined by combining BONCAT with rRNA-targeted fluorescence in situ hybridization (BONCAT-FISH). In theory, BONCAT-labeled cells could be isolated with fluorescence-activated cell sorting (BONCAT-FACS) for subsequent genetic analyses. Here, in the first application, to our knowledge, of BONCAT-FISH and BONCAT-FACS within an environmental context, we probemore » the translational activity of microbial consortia catalyzing the anaerobic oxidation of methane (AOM), a dominant sink of methane in the ocean. These consortia, which typically are composed of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria, have been difficult to study due to their slow in situ growth rates, and fundamental questions remain about their ecology and diversity of interactions occurring between ANME and associated partners. Our activity-correlated analyses of > 16,400 microbial aggregates provide the first evidence, to our knowledge, that AOM consortia affiliated with all five major ANME clades are concurrently active under controlled conditions. Surprisingly, sorting of individual BONCAT-labeled consortia followed by whole-genome amplification and 16S rRNA gene sequencing revealed previously unrecognized interactions of ANME with members of the poorly understood phylum Verrucomicrobia. This finding, together with our observation that ANME-associated Verrucomicrobia are found in a variety of geographically distinct methane seep environments, suggests a broader range of symbiotic relationships within AOM consortia than previously thought.« less

  1. Visualizing in situ translational activity for identifying and sorting slow-growing archaeal-bacterial consortia

    DOE PAGES

    Hatzenpichler, Roland; Connon, Stephanie A.; Goudeau, Danielle; ...

    2016-06-28

    To understand the biogeochemical roles of microorganisms in the environment, it is important to determine when and under which conditions they are metabolically active. Bioorthogonal noncanonical amino acid tagging (BONCAT) can reveal active cells by tracking the incorporation of synthetic amino acids into newly synthesized proteins. The phylogenetic identity of translationally active cells can be determined by combining BONCAT with rRNA-targeted fluorescence in situ hybridization (BONCAT-FISH). In theory, BONCAT-labeled cells could be isolated with fluorescence-activated cell sorting (BONCAT-FACS) for subsequent genetic analyses. Here, in the first application, to our knowledge, of BONCAT-FISH and BONCAT-FACS within an environmental context, we probemore » the translational activity of microbial consortia catalyzing the anaerobic oxidation of methane (AOM), a dominant sink of methane in the ocean. These consortia, which typically are composed of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria, have been difficult to study due to their slow in situ growth rates, and fundamental questions remain about their ecology and diversity of interactions occurring between ANME and associated partners. Our activity-correlated analyses of > 16,400 microbial aggregates provide the first evidence, to our knowledge, that AOM consortia affiliated with all five major ANME clades are concurrently active under controlled conditions. Surprisingly, sorting of individual BONCAT-labeled consortia followed by whole-genome amplification and 16S rRNA gene sequencing revealed previously unrecognized interactions of ANME with members of the poorly understood phylum Verrucomicrobia. This finding, together with our observation that ANME-associated Verrucomicrobia are found in a variety of geographically distinct methane seep environments, suggests a broader range of symbiotic relationships within AOM consortia than previously thought.« less

  2. Myxomycete (slime mold) spores: unrecognized aeroallergens?

    PubMed

    Lierl, Michelle B

    2013-12-01

    Myxomycete spores are present in the outdoor air but have not been studied for allergenicity. To determine whether patients with seasonal allergic rhinitis (SAR) symptoms are sensitized to myxomycete spores. Myxomycete specimens were collected in the field. Nine species of myxomycetes were collected and identified: Arcyria cinerea, Ceratiomyxa fruticulosa, Fuligo septica, Hemitrichia clavata, Lycogala epidendrum, Metatrichia vesparium, Stemonitis nigrescens, Tubifera ferruginosa, and Trichea favoginea. Allergen extracts were made for each species. Protein content of each extract was measured by bicinchoninic acid assay. Protein electrophoresis was performed. Subjects with a history of SAR symptoms were enrolled, and allergy skin prick testing was performed with each extract. Protein content of the extracts ranged from 1.05 to 5.8 mg/mL. Protein bands were seen at 10 to 250 kD. Allergy prick testing was performed in 69 subjects; 42% of subjects had positive prick test results for at least 1 myxomycete extract, with 9% to 22% reacting to each extract. Five of the 12 subjects who tested negative for all allergens on the standard aeroallergen panel had positive prick test results for myxomycetes. Forty-two percent of subjects with SAR were sensitized to myxomycete spores. A significant subset of subjects who had SAR symptoms and otherwise negative skin test results showed sensitization to myxomycetes. These spores are present in the outdoor air during the summer and autumn and might be significant aeroallergens. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Meningitis-retention syndrome. An unrecognized clinical condition.

    PubMed

    Sakakibara, Ryuji; Uchiyama, Tomoyuki; Liu, Zhi; Yamamoto, Tatsuya; Ito, Takashi; Uzawa, Akiyuki; Suenaga, Tadahiro; Kanai, Kazuaki; Awa, Yusuke; Sugiyama, Yoshiki; Hattori, Takamichi

    2005-12-01

    A combination of acute urinary retention and aseptic meningitis has not been well known. This combination can be referred to as meningitis-retention syndrome (MRS), when accompanied by no other abnormalities. To describe the results of a uro-neurological assessment in our patients with MRS. In three patients (two men, one woman; age, 34-68 years), we performed urodynamic studies and relevant imaging and neurophysiological tests, in addition to cerebrospinal fluid (CSF) examination. All three patients developed acute urinary retention along with headache, fever and stiff neck. None had obvious neurological abnormalities, other than a slightly brisk reflex in the lower extremities. One had previously experienced generalized erythematous eruptions, but none had pain, hypalgesia or skin eruptions in the sacral dermatomes suggestive of Elsberg syndrome (infectious sacral polyradiculitis; mostly genital herpes). Brain/spinal/lumbar plexus MRI scans and nerve conduction studies were normal. CSF examination showed mild mononuclear pleocytosis, increased protein content, and normal to mildly decreased glucose content in all patients; increased myelin basic protein suggestive of central nervous system demyelination in one; and increased viral titers in none. Urodynamic study revealed, during the voiding phase, an underactive detrusor in all patients and an unrelaxing sphincter in one. These clinical manifestations were ameliorated within 3 weeks. We reported three cases of MRS, a peculiar syndrome that could be regarded as a mild variant of acute disseminated encephalomyelitis (ADEM). Urinary retention might reflect acute shock phase of this disorder. Although MRS has a benign and self-remitting course, management of the acute urinary retention is necessary.

  4. Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause of hereditary sensory neuropathy type I.

    PubMed

    Guelly, Christian; Zhu, Peng-Peng; Leonardis, Lea; Papić, Lea; Zidar, Janez; Schabhüttl, Maria; Strohmaier, Heimo; Weis, Joachim; Strom, Tim M; Baets, Jonathan; Willems, Jan; De Jonghe, Peter; Reilly, Mary M; Fröhlich, Eleonore; Hatz, Martina; Trajanoski, Slave; Pieber, Thomas R; Janecke, Andreas R; Blackstone, Craig; Auer-Grumbach, Michaela

    2011-01-07

    Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal-dominant hereditary motor and sensory neuropathy distinguished by prominent sensory loss that leads to painless injuries. Unrecognized, these can result in delayed wound healing and osteomyelitis, necessitating distal amputations. To elucidate the genetic basis of an HSN I subtype in a family in which mutations in the few known HSN I genes had been excluded, we employed massive parallel exon sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited reduced GTPase activity and prominently disrupted ER network morphology when expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in 115 additional HSN I patients identified two further dominant ATL1 mutations (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies HSN I and SPG3A as allelic disorders.

  5. Recent meta-analyses neglect previous systematic reviews and meta-analyses about the same topic: a systematic examination.

    PubMed

    Helfer, Bartosz; Prosser, Aaron; Samara, Myrto T; Geddes, John R; Cipriani, Andrea; Davis, John M; Mavridis, Dimitris; Salanti, Georgia; Leucht, Stefan

    2015-04-14

    As the number of systematic reviews is growing rapidly, we systematically investigate whether meta-analyses published in leading medical journals present an outline of available evidence by referring to previous meta-analyses and systematic reviews. We searched PubMed for recent meta-analyses of pharmacological treatments published in high impact factor journals. Previous systematic reviews and meta-analyses were identified with electronic searches of keywords and by searching reference sections. We analyzed the number of meta-analyses and systematic reviews that were cited, described and discussed in each recent meta-analysis. Moreover, we investigated publication characteristics that potentially influence the referencing practices. We identified 52 recent meta-analyses and 242 previous meta-analyses on the same topics. Of these, 66% of identified previous meta-analyses were cited, 36% described, and only 20% discussed by recent meta-analyses. The probability of citing a previous meta-analysis was positively associated with its publication in a journal with a higher impact factor (odds ratio, 1.49; 95% confidence interval, 1.06 to 2.10) and more recent publication year (odds ratio, 1.19; 95% confidence interval 1.03 to 1.37). Additionally, the probability of a previous study being described by the recent meta-analysis was inversely associated with the concordance of results (odds ratio, 0.38; 95% confidence interval, 0.17 to 0.88), and the probability of being discussed was increased for previous studies that employed meta-analytic methods (odds ratio, 32.36; 95% confidence interval, 2.00 to 522.85). Meta-analyses on pharmacological treatments do not consistently refer to and discuss findings of previous meta-analyses on the same topic. Such neglect can lead to research waste and be confusing for readers. Journals should make the discussion of related meta-analyses mandatory.

  6. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder.

    PubMed

    Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

    2009-06-21

    Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.

  7. An Irish outbreak of New Delhi metallo-β-lactamase (NDM)-1 carbapenemase-producing Enterobacteriaceae: increasing but unrecognized prevalence.

    PubMed

    O'Connor, C; Cormican, M; Boo, T W; McGrath, E; Slevin, B; O'Gorman, A; Commane, M; Mahony, S; O'Donovan, E; Powell, J; Monahan, R; Finnegan, C; Kiernan, M G; Coffey, J C; Power, L; O'Connell, N H; Dunne, C P

    2016-12-01

    Carbapenemase-producing Enterobacteriaceae (CPE) may cause healthcare-associated infections with high mortality rates. New Delhi metallo-β-lactamase-1 (NDM-1) is among the most recently discovered carbapenemases. To report the first outbreak of NDM-1 CPE in Ireland, including microbiological and epidemiological characteristics, and assessing the impact of infection prevention and control measures. This was a retrospective microbiological and epidemiological review. Cases were defined as patients with a CPE-positive culture. Contacts were designated as roommates or ward mates. This outbreak involved 10 patients with a median age of 71 years (range: 45-90), located in three separate but affiliated healthcare facilities. One patient was infected (the index case); the nine others were colonized. Nine NDM-1-producing Klebsiella pneumoniae, an NDM-1-producing Escherichia coli and a K. pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae were detected between week 24, 2014 and week 37, 2014. Pulsed-field gel electrophoresis demonstrated similarity. NDM-1-positive isolates were meropenem resistant with minimum inhibitory concentrations (MICs) ranging from 12 to 32 μg/mL. All were tigecycline susceptible (MICs ≤1 μg/mL). One isolate was colistin resistant (MIC 4.0 μg/mL; mcr-1 gene not detected). In 2015, four further NDM-1 isolates were detected. The successful management of this outbreak was achieved via the prompt implementation of enhanced infection prevention and control practices to prevent transmission. These patients did not have a history of travel outside of Ireland, but several had frequent hospitalizations in Ireland, raising concerns regarding the possibility of increasing but unrecognized prevalence of NDM-1 and potential decline in value of travel history as a marker of colonization risk. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  8. Systematics of Vampyressa melissa Thomas, 1926 (Chiroptera, Phyllostomidae), with descriptions of two new species of Vampyressa

    USGS Publications Warehouse

    Tavares, Valéria da C.; Gardner, Alfred L.; Ramírez-Chaves, Héctor E.; Velazco, Paúl M.

    2014-01-01

    Vampyressa melissa is a poorly known phyllostomid bat listed as vulnerable by the International Union for Conservation of Nature (IUCN). Since its description in 1926, fewer than 40 V. melissa have been reported in the literature, and less than half of these may have been correctly identified. During revisionary studies of Vampyressa, we uncovered two previously unrecognized species related to V. melissa, all associated with higher elevation habitats (>1400 m), one from the Andes of Colombia (Vampyressa sinchi, new species) and the other from western Panama (Vampyressa elisabethae, new species) revealing that V. melissa, as traditionally defined, is a composite of at least three species. In this paper, we provide a restricted diagnosis for the genus Vampyressa, an emended diagnosis of V. melissa, and descriptions of the two new species. The separation of these frugivorous bats, previously identified as V. melissa, into three isolated upper-elevation species, each having restricted distributions further highlights their fragile conservation status.

  9. Using a New Crustal Thickness Model to Test Previous Candidate Lunar Basins and to Search for New Candidates

    NASA Technical Reports Server (NTRS)

    Meyer, H. M.; Frey, H. V.

    2012-01-01

    A new crustal thickness model was used to test the viability of 110 candidate large lunar basins previously identified using older topographic and crustal thickness data as well as photogeologic data. The new model was also used to search for new candidate lunar basins greater than 300 km in diameter. We eliminated 11 of 27 candidates previously identified in the older crustal thickness model, and found strong evidence for at least 8 new candidates.

  10. Fine-mapping the human leukocyte antigen locus in rheumatoid arthritis and other rheumatic diseases: identifying causal amino acid variants?

    PubMed

    van Heemst, Jurgen; Huizinga, Tom J W; van der Woude, Diane; Toes, René E M

    2015-05-01

    To provide an update on and the context of the recent findings obtained with novel statistical methods on the association of the human leukocyte antigen (HLA) locus with rheumatic diseases. Novel single nucleotide polymorphism fine-mapping data obtained for the HLA locus have indicated the strongest association with amino acid positions 11 and 13 of HLA-DRB1 molecule for several rheumatic diseases. On the basis of these data, a dominant role for position 11/13 in driving the association with these diseases is proposed and the identification of causal variants in the HLA region in relation to disease susceptibility implicated. The HLA class II locus is the most important risk factor for several rheumatic diseases. Recently, new statistical approaches have identified previously unrecognized amino acid positions in the HLA-DR molecule that associate with anticitrullinated protein antibody-negative and anticitrullinated protein antibody-positive rheumatoid arthritis. Likewise, similar findings have been made for other rheumatic conditions such as giant-cell arteritis and systemic lupus erythematosus. Interestingly, all these studies point toward an association with the same amino acid positions: amino acid positions 11 and 13 of the HLA-DR β chain. As both these positions influence peptide binding by HLA-DR and have been implicated in antigen presentation, the novel fine-mapping approach is proposed to map causal variants in the HLA region relevant to rheumatoid arthritis and several rheumatic diseases. If these interpretations are correct, they would direct the biological research aiming to address the explanation for the HLA-disease association. Here, we provide an overview of the recent findings and evidence from literature that, although relevant new insights have been obtained on HLA-disease associations, the interpretation of the biological role of these amino acids as causal variants explaining that such associations should be taken with caution.

  11. PAPERCLIP identifies microRNA targets and a role of CstF64/64tau in promoting non-canonical poly(A) site usage

    PubMed Central

    Hwang, Hun-Way; Park, Christopher Y.; Goodarzi, Hani; Fak, John J.; Mele, Aldo; Moore, Michael J.; Saito, Yuhki; Darnell, Robert B.

    2016-01-01

    Accurate and precise annotation of the 3′ untranslated regions (3′ UTRs) is critical in understanding how mRNAs are regulated by microRNAs (miRNAs) and RNA-binding proteins (RBPs). Here we describe a method, PAPERCLIP (Poly(A) binding Protein-mediated mRNA 3′ End Retrieval by CrossLinking ImmunoPrecipitation), which shows high specificity for the mRNA 3′ ends and compares favorably to existing 3′ end mapping methods. PAPERCLIP uncovers a previously unrecognized role of CstF64/64tau in promoting the usage of a selected group of non-canonical poly(A) sites, the majority of them containing a downstream GUKKU motif. Furthermore, in mouse brain, PAPERCLIP discovers extended 3′ UTR sequences harboring functional miRNA binding sites and reveals developmentally regulated APA shifts including one in Atp2b2 that is evolutionarily conserved in human and results in a gain of a functional binding site of miR-137. PAPERCLIP provides a powerful tool to decipher post-transcriptional regulation of mRNAs through APA in vivo. PMID:27050522

  12. Distribution of trace elements in drilling chip samples around a roll-type uranium deposit, San Juan Basin, New Mexico

    USGS Publications Warehouse

    Day, H.C.; Spirakis, C.S.; Zech, R.S.; Kirk, A.R.

    1983-01-01

    Chip samples from rotary drilling in the vicinity of a roll-type uranium deposit in the southwestern San Juan Basin were split into a whole-washed fraction, a clay fraction, and a heavy mineral concentrate fraction. Analyses of these fractions determined that cutting samples could be used to identify geochemical halos associated with this ore deposit. In addition to showing a distribution of selenium, uranium, vanadium, and molybdenum similar to that described by Harshman (1974) in uranium roll-type deposits in Wyoming, South Dakota, and Texas, the chemical data indicate a previously unrecognized zinc anomaly in the clay fraction downdip of the uranium ore.

  13. Translocation 4p;21q identified by FISH in a case previously described as {open_quotes}presumptive monosomy 21{close_quotes}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yao, Xiu-Lan; Jenkins, E.C.

    1994-10-01

    Recently, Lopez-Pajares et al. (1993) reported identification of a translocation between the short arm of a chromosome 5 and the long arm of a chromosome 21 in a patient who was thought to be monosomy 21. This study is the first application of a chromosome 21 painting probe, pBS-21, and fluorescent in situ chromosome hybridization (FISH) to revise an earlier diagnosis of monosomy 21. We have now restudied skin fibroblast cultures, GM00137B, that are still available from another patient previously described as {open_quotes}presumptive monosomy 21{close_quotes} and have found that this case also has a translocation involving chromosomes 21 and 4.more » The authors urge that all previous cases of what appeared to be monosomy 21 should be re-examined with FISH to confirm or revise the original diagnosis so that genetic counseling of the family may be updated. 3 refs., 3 figs.« less

  14. Haemophilus influenzae type f meningitis in a previously healthy boy

    PubMed Central

    Ronit, Andreas; Berg, Ronan M G; Bruunsgaard, Helle; Plovsing, Ronni R

    2013-01-01

    Non-serotype b strains of Haemophilus influenzae are extremely rare causes of acute bacterial meningitis in immunocompetent individuals. We report a case of acute bacterial meningitis in a 14-year-old boy, who was previously healthy and had been immunised against H influenzae serotype b (Hib). The causative pathogen was identified as H influenzae serotype f (Hif), and was successfully treated with ceftriaxone. An immunological evaluation revealed transient low levels of immunoglobulins but no apparent immunodeficiency was found 2 years after the clinical insult. PMID:23645639

  15. Haemophilus influenzae type f meningitis in a previously healthy boy.

    PubMed

    Ronit, Andreas; Berg, Ronan M G; Bruunsgaard, Helle; Plovsing, Ronni R

    2013-05-02

    Non-serotype b strains of Haemophilus influenzae are extremely rare causes of acute bacterial meningitis in immunocompetent individuals. We report a case of acute bacterial meningitis in a 14-year-old boy, who was previously healthy and had been immunised against H influenzae serotype b (Hib). The causative pathogen was identified as H influenzae serotype f (Hif), and was successfully treated with ceftriaxone. An immunological evaluation revealed transient low levels of immunoglobulins but no apparent immunodeficiency was found 2 years after the clinical insult.

  16. Adenoid cystic carcinoma of the nasopharynx after previous adenoid irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sofferman, R.A.; Heisse, J.W. Jr.

    1985-04-01

    In 1978, Pratt challenged the otolaryngology community to identify an incidence of malignancy in individuals who have previously received radium therapy to the nasopharyngeal lymphoid tissues. This case report is a direct response to that quest and presents a well documented adenoid cystic carcinoma evolving 23 years after radium applicator treatment to the fossa of Rosenmuller. Although a cause-and-effect relationship cannot be scientifically proven, the case history raises several important questions concerning the stimulating effects of radiation on the later onset of frank malignancy.

  17. Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

    PubMed Central

    Zubair, Niha; Luis Ambite, Jose; Bush, William S.; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne H-H.; Absher, Devin; Assimes, Themistocles L.; Bielinski, Suzette J.; Bottinger, Erwin P.; Buzkova, Petra; Chuang, Lee-Ming; Chung, Ren-Hua; Cochran, Barbara; Dumitrescu, Logan; Gottesman, Omri; Haessler, Jeffrey W.; Haiman, Christopher; Heiss, Gerardo; Hsiung, Chao A.; Hung, Yi-Jen; Hwu, Chii-Min; Juang, Jyh-Ming J.; Le Marchand, Loic; Lee, I-Te; Lee, Wen-Jane; Lin, Li-An; Lin, Danyu; Lin, Shih-Yi; Mackey, Rachel H.; Martin, Lisa W.; Pasaniuc, Bogdan; Peters, Ulrike; Predazzi, Irene; Quertermous, Thomas; Reiner, Alex P.; Robinson, Jennifer; Rotter, Jerome I.; Ryckman, Kelli K.; Schreiner, Pamela J.; Stahl, Eli; Tao, Ran; Tsai, Michael Y.; Waite, Lindsay L.; Wang, Tzung-Dau; Buyske, Steven; Ida Chen, Yii-Der; Cheng, Iona; Crawford, Dana C.; Loos, Ruth J.F.; Rich, Stephen S.; Fornage, Myriam; North, Kari E.; Kooperberg, Charles; Carty, Cara L.

    2016-01-01

    Abstract Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies. PMID:28426890

  18. Do emotional intelligence and previous caring experience influence student nurse performance? A comparative analysis.

    PubMed

    Stenhouse, Rosie; Snowden, Austyn; Young, Jenny; Carver, Fiona; Carver, Hannah; Brown, Norrie

    2016-08-01

    Reports of poor nursing care have focused attention on values based selection of candidates onto nursing programmes. Values based selection lacks clarity and valid measures. Previous caring experience might lead to better care. Emotional intelligence (EI) might be associated with performance, is conceptualised and measurable. To examine the impact of 1) previous caring experience, 2) emotional intelligence 3) social connection scores on performance and retention in a cohort of first year nursing and midwifery students in Scotland. A longitudinal, quasi experimental design. Adult and mental health nursing, and midwifery programmes in a Scottish University. Adult, mental health and midwifery students (n=598) completed the Trait Emotional Intelligence Questionnaire-short form and Schutte's Emotional Intelligence Scale on entry to their programmes at a Scottish University, alongside demographic and previous caring experience data. Social connection was calculated from a subset of questions identified within the TEIQue-SF in a prior factor and Rasch analysis. Student performance was calculated as the mean mark across the year. Withdrawal data were gathered. 598 students completed baseline measures. 315 students declared previous caring experience, 277 not. An independent-samples t-test identified that those without previous caring experience scored higher on performance (57.33±11.38) than those with previous caring experience (54.87±11.19), a statistically significant difference of 2.47 (95% CI, 0.54 to 4.38), t(533)=2.52, p=.012. Emotional intelligence scores were not associated with performance. Social connection scores for those withdrawing (mean rank=249) and those remaining (mean rank=304.75) were statistically significantly different, U=15,300, z=-2.61, p$_amp_$lt;0.009. Previous caring experience led to worse performance in this cohort. Emotional intelligence was not a useful indicator of performance. Lower scores on the social connection factor were associated

  19. MUSI: an integrated system for identifying multiple specificity from very large peptide or nucleic acid data sets.

    PubMed

    Kim, Taehyung; Tyndel, Marc S; Huang, Haiming; Sidhu, Sachdev S; Bader, Gary D; Gfeller, David; Kim, Philip M

    2012-03-01

    Peptide recognition domains and transcription factors play crucial roles in cellular signaling. They bind linear stretches of amino acids or nucleotides, respectively, with high specificity. Experimental techniques that assess the binding specificity of these domains, such as microarrays or phage display, can retrieve thousands of distinct ligands, providing detailed insight into binding specificity. In particular, the advent of next-generation sequencing has recently increased the throughput of such methods by several orders of magnitude. These advances have helped reveal the presence of distinct binding specificity classes that co-exist within a set of ligands interacting with the same target. Here, we introduce a software system called MUSI that can rapidly analyze very large data sets of binding sequences to determine the relevant binding specificity patterns. Our pipeline provides two major advances. First, it can detect previously unrecognized multiple specificity patterns in any data set. Second, it offers integrated processing of very large data sets from next-generation sequencing machines. The results are visualized as multiple sequence logos describing the different binding preferences of the protein under investigation. We demonstrate the performance of MUSI by analyzing recent phage display data for human SH3 domains as well as microarray data for mouse transcription factors.

  20. Xyleborus bispinatus reared on artificial media using sawdust from avocado or silkbay in presence or absence of the laurel wilt pathogen (Raffaelea lauricola)

    USDA-ARS?s Scientific Manuscript database

    Xyleborus bispinatus Eichhoff (Coleoptera: Curculionidae: Scolytinae) was reported in Florida for the first time in 2013. Previously, it was unrecognized and not distinguished from the morphologically similar Xyleborus ferrugineus (F.). Like other members of the tribe Xyleborini, X. ferrugineus (and...

  1. Xyleborus bispinatus (Coleoptera: Curculionidae) reared on artificial media using sawdust from avocado or silkbay in presence or absence of the laurel wilt pathogen (Raffaelea lauricola).

    USDA-ARS?s Scientific Manuscript database

    Xyleborus bispinatus Eichhoff (Coleoptera: Curculionidae) was reported in Florida for the first time in 2013. Previously, it was unrecognized and not distinguished from the morphologically similar Xyleborus ferrugineus (F.). Like other members of the tribe Xyleborini, X. ferrugineus (and possibly X....

  2. 36 CFR 60.14 - Changes and revisions to properties listed in the National Register.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... previously unrecognized significance in American history, architecture, archeology, engineering or culture... would be adversely affected by the intrusion of the property; and (iv) Photographs showing the proposed... adversely affected by intrusion of the property. In addition, new photographs, acreage, verbal boundary...

  3. 36 CFR 60.14 - Changes and revisions to properties listed in the National Register.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... previously unrecognized significance in American history, architecture, archeology, engineering or culture... would be adversely affected by the intrusion of the property; and (iv) Photographs showing the proposed... adversely affected by intrusion of the property. In addition, new photographs, acreage, verbal boundary...

  4. 36 CFR 60.14 - Changes and revisions to properties listed in the National Register.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... previously unrecognized significance in American history, architecture, archeology, engineering or culture... would be adversely affected by the intrusion of the property; and (iv) Photographs showing the proposed... adversely affected by intrusion of the property. In addition, new photographs, acreage, verbal boundary...

  5. 36 CFR 60.14 - Changes and revisions to properties listed in the National Register.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... previously unrecognized significance in American history, architecture, archeology, engineering or culture... would be adversely affected by the intrusion of the property; and (iv) Photographs showing the proposed... adversely affected by intrusion of the property. In addition, new photographs, acreage, verbal boundary...

  6. Hymenolepis folkertsi n. sp. (Eucestoda: Hymenolepididae) in the oldfield mouse Peromyscus polionotus from the southeastern Nearctic with comments on tapeworm faunal diversity among deer mice

    USDA-ARS?s Scientific Manuscript database

    A previously unrecognized species of hymenolepidid cestode attributable to Hymenolepis Weinland, 1858 is described based on specimens in Peromyscus polionotus, oldfield mouse, from Georgia near the southeastern coast of continental North America. Specimens of Hymenolepis folkertsi n. sp. differ from...

  7. Diversity at the Holarctic nexus: species of Arostrilepis (Eucestoda: Hymenolepididae) in arvicoline rodents (Cricetidae: Arvicolinae) from greater Beringia

    USDA-ARS?s Scientific Manuscript database

    Previously unrecognized species of hymenolepidid cestodes attributable to Arostrilepis Mas-Coma & Tenora, 1997 in arvicoline rodents from the greater Beringian region and western North America are described. Discovery and characterization of these tapeworms contributes to the recognition of a compl...

  8. 78 FR 12995 - Airworthiness Directives; Gulfstream Aerospace LP (Type Certificate Previously Held by Israel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... Aerospace LP (Type Certificate Previously Held by Israel Aircraft Industries, Ltd.) Airplanes AGENCY... propose to supersede an existing airworthiness directive (AD) that applies to all Gulfstream Aerospace... information identified in this proposed AD, contact Gulfstream Aerospace Corporation, P.O. Box 2206, Mail...

  9. Dietary self-efficacy predicts AHEI diet quality in women with previous gestational diabetes.

    PubMed

    Ferranti, Erin Poe; Narayan, K M Venkat; Reilly, Carolyn M; Foster, Jennifer; McCullough, Marjorie; Ziegler, Thomas R; Guo, Ying; Dunbar, Sandra B

    2014-01-01

    The purpose of this study was to examine the association of intrapersonal influences of diet quality as defined by the Health Belief Model constructs in women with recent histories of gestational diabetes. A descriptive, correlational, cross-sectional design was used to analyze relationships between diet quality and intrapersonal variables, including perceptions of threat of type 2 diabetes mellitus development, benefits and barriers of healthy eating, and dietary self-efficacy, in a convenience sample of 75 community-dwelling women (55% minority; mean age, 35.5 years; SD, 5.5 years) with previous gestational diabetes mellitus. Diet quality was defined by the Alternative Healthy Eating Index (AHEI). Multiple regression was used to identify predictors of AHEI diet quality. Women had moderate AHEI diet quality (mean score, 47.6; SD, 14.3). Only higher levels of education and self-efficacy significantly predicted better AHEI diet quality, controlling for other contributing variables. There is a significant opportunity to improve diet quality in women with previous gestational diabetes mellitus. Improving self-efficacy may be an important component to include in nutrition interventions. In addition to identifying other important individual components, future studies of diet quality in women with previous gestational diabetes mellitus are needed to investigate the scope of influence beyond the individual to potential family, social, and environmental factors. © 2014 The Author(s).

  10. Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci.

    PubMed

    Zubair, Niha; Graff, Mariaelisa; Luis Ambite, Jose; Bush, William S; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne H-H; Absher, Devin; Assimes, Themistocles L; Bielinski, Suzette J; Bottinger, Erwin P; Buzkova, Petra; Chuang, Lee-Ming; Chung, Ren-Hua; Cochran, Barbara; Dumitrescu, Logan; Gottesman, Omri; Haessler, Jeffrey W; Haiman, Christopher; Heiss, Gerardo; Hsiung, Chao A; Hung, Yi-Jen; Hwu, Chii-Min; Juang, Jyh-Ming J; Le Marchand, Loic; Lee, I-Te; Lee, Wen-Jane; Lin, Li-An; Lin, Danyu; Lin, Shih-Yi; Mackey, Rachel H; Martin, Lisa W; Pasaniuc, Bogdan; Peters, Ulrike; Predazzi, Irene; Quertermous, Thomas; Reiner, Alex P; Robinson, Jennifer; Rotter, Jerome I; Ryckman, Kelli K; Schreiner, Pamela J; Stahl, Eli; Tao, Ran; Tsai, Michael Y; Waite, Lindsay L; Wang, Tzung-Dau; Buyske, Steven; Ida Chen, Yii-Der; Cheng, Iona; Crawford, Dana C; Loos, Ruth J F; Rich, Stephen S; Fornage, Myriam; North, Kari E; Kooperberg, Charles; Carty, Cara L

    2016-12-15

    Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Previous Experience Not Required: Contextualizing the Choice to Teach School-Based Agricultural Education

    ERIC Educational Resources Information Center

    Marx, Adam A.; Smith, Amy R.; Smalley, Scott W.; Miller, Courtney

    2017-01-01

    The purpose of this study was to identify key career choice items which lead students without previous experience in school-based agricultural education (SBAE) to pursuing agricultural education. The Ag Ed FIT-Choice® model adapted by Lawver (2009) and developed by Richardson and Watt (2006) provided the investigative framework to design this…

  12. Evaluation of an interdisciplinary re-isolation policy for patients with previous Clostridium difficile diarrhea.

    PubMed

    Boone, N; Eagan, J A; Gillern, P; Armstrong, D; Sepkowitz, K A

    1998-12-01

    Diarrhea caused by Clostridium difficile is increasingly recognized as a nosocomial problem. The effectiveness and cost of a new program to decrease nosocomial spread by identifying patients scheduled for readmission who were previously positive for toxin was evaluated. The Memorial Sloan-Kettering Cancer Center is a 410-bed comprehensive cancer center in New York City. Many patients are readmitted during their course of cancer therapy. In 1995 as a result of concern about the nosocomial spread of C difficile, we implemented a policy that all patients who were positive for C difficile toxin in the previous 6 months with no subsequent toxin-negative stool as an outpatient would be placed into contact isolation on readmission pending evaluation of stool specimens. Patients who were previously positive for C difficile toxin were identified to infection control and admitting office databases via computer. Admitting personnel contacted infection control with all readmissions to determine whether a private room was required. Between July 1, 1995, and June 30, 1996, 47 patients who were previously positive for C difficile toxin were readmitted. Before their first scheduled readmission, the specimens for 15 (32%) of these patients were negative for C difficile toxin. They were subsequently cleared as outpatients and were readmitted without isolation. Workup of the remaining 32 patients revealed that the specimens for 7 patients were positive for C difficile toxin and 86 isolation days were used. An additional 25 patients used 107 isolation days and were either cleared after a negative specimen was obtained in-house or discharged without having an appropriate specimen sent. Four patients (9%) had reoccurring C difficile after having toxin-negative stools. We estimate (because outpatient specimens were not collected) the cost incurred at $48,500 annually, including the incremental cost of hospital isolation and equipment. Our policy to control the spread of nosocomial C

  13. Targeted High-Throughput Sequencing Identifies Mutations in atlastin-1 as a Cause of Hereditary Sensory Neuropathy Type I

    PubMed Central

    Guelly, Christian; Zhu, Peng-Peng; Leonardis, Lea; Papić, Lea; Zidar, Janez; Schabhüttl, Maria; Strohmaier, Heimo; Weis, Joachim; Strom, Tim M.; Baets, Jonathan; Willems, Jan; De Jonghe, Peter; Reilly, Mary M.; Fröhlich, Eleonore; Hatz, Martina; Trajanoski, Slave; Pieber, Thomas R.; Janecke, Andreas R.; Blackstone, Craig; Auer-Grumbach, Michaela

    2011-01-01

    Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal-dominant hereditary motor and sensory neuropathy distinguished by prominent sensory loss that leads to painless injuries. Unrecognized, these can result in delayed wound healing and osteomyelitis, necessitating distal amputations. To elucidate the genetic basis of an HSN I subtype in a family in which mutations in the few known HSN I genes had been excluded, we employed massive parallel exon sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited reduced GTPase activity and prominently disrupted ER network morphology when expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in 115 additional HSN I patients identified two further dominant ATL1 mutations (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies HSN I and SPG3A as allelic disorders. PMID:21194679

  14. Twelve previously unknown phage genera are ubiquitous in global oceans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Holmfeldt, Karin; Solonenko, Natalie; Shah, Manesh B

    Viruses are fundamental to ecosystems ranging from oceans to humans, yet our ability to study them is bottlenecked by the lack of ecologically relevant isolates, resulting in unknowns dominating culture-independent surveys. Here we present genomes from 31 phages infecting multiple strains of the aquatic bacterium Cellulophaga baltica (Bacteroidetes) to provide data for an underrepresented and environmentally abundant bacterial lineage. Comparative genomics delineated 12 phage groups that (i) each represent a new genus, and (ii) represent one novel and four wellknown viral families. This diversity contrasts the few well-studied marine phage systems, but parallels the diversity of phages infecting human-associated bacteria.more » Although all 12 Cellulophaga phages represent new genera, the podoviruses and icosahedral, nontailed ssDNA phages were exceptional, with genomes up to twice as large as those previously observed for each phage type. Structural novelty was also substantial, requiring experimental phage proteomics to identify 83% of the structural proteins. The presence of uncommon nucleotide metabolism genes in four genera likely underscores the importance of scavenging nutrient-rich molecules as previously seen for phages in marine environments. Metagenomic recruitment analyses suggest that these particular Cellulophaga phages are rare and may represent a first glimpse into the phage side of the rare biosphere. However, these analyses also revealed that these phage genera are widespread, occurring in 94% of 137 investigated metagenomes. Together, this diverse and novel collection of phages identifies a small but ubiquitous fraction of unknown marine viral diversity and provides numerous environmentally relevant phage host systems for experimental hypothesis testing.« less

  15. Twelve previously unknown phage genera are ubiquitous in global oceans.

    PubMed

    Holmfeldt, Karin; Solonenko, Natalie; Shah, Manesh; Corrier, Kristen; Riemann, Lasse; Verberkmoes, Nathan C; Sullivan, Matthew B

    2013-07-30

    Viruses are fundamental to ecosystems ranging from oceans to humans, yet our ability to study them is bottlenecked by the lack of ecologically relevant isolates, resulting in "unknowns" dominating culture-independent surveys. Here we present genomes from 31 phages infecting multiple strains of the aquatic bacterium Cellulophaga baltica (Bacteroidetes) to provide data for an underrepresented and environmentally abundant bacterial lineage. Comparative genomics delineated 12 phage groups that (i) each represent a new genus, and (ii) represent one novel and four well-known viral families. This diversity contrasts the few well-studied marine phage systems, but parallels the diversity of phages infecting human-associated bacteria. Although all 12 Cellulophaga phages represent new genera, the podoviruses and icosahedral, nontailed ssDNA phages were exceptional, with genomes up to twice as large as those previously observed for each phage type. Structural novelty was also substantial, requiring experimental phage proteomics to identify 83% of the structural proteins. The presence of uncommon nucleotide metabolism genes in four genera likely underscores the importance of scavenging nutrient-rich molecules as previously seen for phages in marine environments. Metagenomic recruitment analyses suggest that these particular Cellulophaga phages are rare and may represent a first glimpse into the phage side of the rare biosphere. However, these analyses also revealed that these phage genera are widespread, occurring in 94% of 137 investigated metagenomes. Together, this diverse and novel collection of phages identifies a small but ubiquitous fraction of unknown marine viral diversity and provides numerous environmentally relevant phage-host systems for experimental hypothesis testing.

  16. Nocturnal hypoglycemia identified by a continuous glucose monitoring system in patients with primary adrenal insufficiency (Addison's Disease).

    PubMed

    Meyer, Gesine; Hackemann, Annika; Reusch, Juergen; Badenhoop, Klaus

    2012-05-01

    Hypoglycemia can be a symptom in patients with Addison's disease. The common regimen of replacement therapy with oral glucocorticoids results in unphysiological low cortisol levels in the early morning, the time of highest insulin sensitivity. Therefore patients with Addison's disease are at risk for unrecognized and potentially severe nocturnal hypoglycemia also because of a disturbed counterregulatory function. Use of a continuous glucose monitoring system (CGMS) could help to adjust hydrocortisone treatment and to avoid nocturnal hypoglycemia in these patients. Thirteen patients with Addison's disease were screened for hypoglycemia wearing a CGMS for 3-5 days. In one patient we identified a hypoglycemic episode at 3:45 a.m. with a blood glucose level of 46 mg/dL, clearly beneath the 95% tolerance interval of minimal glucose levels between 2 and 4 a.m. (53.84 mg/dL). After the hydrocortisone replacement scheme was changed, the minimum blood glucose level between 2 and 4 a.m. normalized to 87 mg/dL. Continuous glucose monitoring can detect nocturnal hypoglycemia in patients with primary adrenal insufficiency and hence prevent in these patients an impaired quality of life and even serious adverse effects.

  17. Clandestine psychopathology: unrecognized dissociative disorders in inpatient psychiatry.

    PubMed

    Ginzburg, Karni; Somer, Eli; Tamarkin, Gali; Kramer, Lilach

    2010-05-01

    Surveys among Israeli mental health professionals found that almost half of them doubt the validity of dissociative disorders (DD) and have no experience in either diagnosing or treating DD patients. These findings, in line with arguments that DDs are socially construed North American phenomena, call for the need to investigate it in Israel. Eighty-one psychiatric inpatients were screened for dissociative pathology. Participants categorized as having low levels of dissociation (n = 26) and those demonstrating high levels of dissociation (n = 22) were asked to participate in a Structured Clinical Interview for the DSM-Dissociative Disorders-Revised. One-quarter of all participants were identified as having probable dissociative psychopathology. Based on the Structured Clinical Interview for the DSM-Dissociative Disorders-Revised, estimates of DD range between 12 and 21%. None of the participants had any indication of a DD diagnosis in their medical records. Diagnosis of personality disorder and psychiatric comorbidity were related to the likelihood of a DD diagnosis and its severity.

  18. Mining the topography and dynamics of the 4D Nucleome to identify novel CNS drug pathways.

    PubMed

    Higgins, Gerald A; Allyn-Feuer, Ari; Georgoff, Patrick; Nikolian, Vahagn; Alam, Hasan B; Athey, Brian D

    2017-07-01

    The pharmacoepigenome can be defined as the active, noncoding province of the genome including canonical spatial and temporal regulatory mechanisms of gene regulation that respond to xenobiotic stimuli. Many psychotropic drugs that have been in clinical use for decades have ill-defined mechanisms of action that are beginning to be resolved as we understand the transcriptional hierarchy and dynamics of the nucleus. In this review, we describe spatial, temporal and biomechanical mechanisms mediated by psychotropic medications. Focus is placed on a bioinformatics pipeline that can be used both for detection of pharmacoepigenomic variants that discretize drug response and adverse events to improve pharmacogenomic testing, and for the discovery of novel CNS therapeutics. This approach integrates the functional topology and dynamics of the transcriptional hierarchy of the pharmacoepigenome, gene variant-driven identification of pharmacogenomic regulatory domains, and mesoscale mapping for the discovery of novel CNS pharmacodynamic pathways in human brain. Examples of the application of this pipeline are provided, including the discovery of valproic acid (VPA) mediated transcriptional reprogramming of neuronal cell fate following injury, and mapping of a CNS pathway glutamatergic pathway for the mood stabilizer lithium. These examples in regulatory pharmacoepigenomics illustrate how ongoing research using the 4D nucleome provides a foundation to further insight into previously unrecognized psychotropic drug pharmacodynamic pathways in the human CNS. Copyright © 2017. Published by Elsevier Inc.

  19. The Use of Technology in Identifying Hospital Malnutrition: Scoping Review.

    PubMed

    Trtovac, Dino; Lee, Joon

    2018-01-19

    Malnutrition is a condition most commonly arising from the inadequate consumption of nutrients necessary to maintain physiological health and is associated with the development of cardiovascular disease, osteoporosis, and sarcopenia. Malnutrition occurring in the hospital setting is caused by insufficient monitoring, identification, and assessment efforts. Furthermore, the ability of health care workers to identify and recognize malnourished patients is suboptimal. Therefore, interventions focusing on the identification and treatment of malnutrition are valuable, as they reduce the risks and rates of malnutrition within hospitals. Technology may be a particularly useful ally in identifying malnutrition due to scalability, timeliness, and effectiveness. In an effort to explore the issue, this scoping review synthesized the availability of technological tools to detect and identify hospital malnutrition. Our objective was to conduct a scoping review of the different forms of technology used in addressing malnutrition among adults admitted to hospital to (1) identify the extent of the published literature on this topic, (2) describe key findings, and (3) identify outcomes. We designed and implemented a search strategy in 3 databases (PubMed, Scopus, and CINAHL). We completed a descriptive numerical summary and analyzed study characteristics. One reviewer independently extracted data from the databases. We retrieved and reviewed a total of 21 articles. We categorized articles by the computerized tool or app type: malnutrition assessment (n=15), food intake monitoring (n=5), or both (n=1). Within those categories, we subcategorized the different technologies as either hardware (n=4), software (n=13), or both (n=4). An additional subcategory under software was cloud-based apps (n=1). Malnutrition in the acute hospital setting was largely an unrecognized problem, owing to insufficient monitoring, identification, and initial assessments of identifying both patients who are

  20. A Different Vision of Education.

    ERIC Educational Resources Information Center

    Nixon, Nicholas; Coles, Robert

    1999-01-01

    Presents photos featuring students from the Perkins School for the Blind (Massachusetts) reprinted from "School," a book by photographer Nicholas Nixon and psychiatrist Robert Coles. Coles says Nixon's focused, confined scenes paradoxically open viewers' minds to previously unimagined or unrecognized possibilities. Photos are accompanied…

  1. Lobectomy is a more Cost-Effective Option than Total Thyroidectomy for 1 to 4 cm Papillary Thyroid Carcinoma that do not Possess Clinically Recognizable High-Risk Features.

    PubMed

    Lang, Brian Hung-Hin; Wong, Carlos K H

    2016-10-01

    Although lobectomy is a viable alternative to total thyroidectomy (TT) in low-risk 1 to 4 cm papillary thyroid carcinoma (PTC), lobectomy is associated with higher locoregional recurrence risk and need for completion TT upon discovery of a previously unrecognized histologic high-risk feature (HRF). The present study evaluated long-term cost-effectiveness between lobectomy and TT. Our base case was a hypothetical female cohort aged 40 years with a low-risk 2.5 cm PTC. A Markov decision tree model was constructed to compare cost-effectiveness between lobectomy and TT after 25 years. Patients with an unrecognized HRF (including aggressive histology, microscopic extrathyroidal extension, lymphovascular invasion, positive resection margin, nodal metastasis >5 mm, and multifocality) underwent completion TT after lobectomy. Outcome probabilities, utilities, and costs were estimated from the literature. The threshold for cost-effectiveness was set at US$50,000/quality-adjusted life-year (QALY). Sensitivity and threshold analyses were used to examine model uncertainty. After 25 years, each patient who underwent lobectomy instead of TT cost an extra US$772.08 but gained an additional 0.300 QALY. The incremental cost-effectiveness ratio was US$2577.65/QALY. In the sensitivity analysis, the lobectomy arm began to become cost-effective only after 3 years. Despite varying the reported prevalence of clinically unrecognized HRFs, complication from surgical procedures, annualized recurrence rates, unit cost of surgical procedure or complication, and utility score, lobectomy remained more cost-effective than TT. Despite the higher locoregional recurrence risk and having almost half of the patients undergoing completion TT after lobectomy upon discovery of a previously unrecognized HRF, initial lobectomy was a more cost-effective long-term option than initial TT for 1 to 4 cm PTCs without clinically recognized HRFs.

  2. Substitutions of short heterologous DNA segments of intragenomic or extragenomic origins produce clustered genomic polymorphisms

    PubMed Central

    Harms, Klaus; Lunnan, Asbjørn; Hülter, Nils; Mourier, Tobias; Vinner, Lasse; Andam, Cheryl P.; Marttinen, Pekka; Fridholm, Helena; Hansen, Anders Johannes; Hanage, William P.; Nielsen, Kaare Magne; Willerslev, Eske; Johnsen, Pål Jarle

    2016-01-01

    In a screen for unexplained mutation events we identified a previously unrecognized mechanism generating clustered DNA polymorphisms such as microindels and cumulative SNPs. The mechanism, short-patch double illegitimate recombination (SPDIR), facilitates short single-stranded DNA molecules to invade and replace genomic DNA through two joint illegitimate recombination events. SPDIR is controlled by key components of the cellular genome maintenance machinery in the gram-negative bacterium Acinetobacter baylyi. The source DNA is primarily intragenomic but can also be acquired through horizontal gene transfer. The DNA replacements are nonreciprocal and locus independent. Bioinformatic approaches reveal occurrence of SPDIR events in the gram-positive human pathogen Streptococcus pneumoniae and in the human genome. PMID:27956618

  3. Asteroid Systems: Binaries, Triples, and Pairs

    NASA Astrophysics Data System (ADS)

    Margot, J.-L.; Pravec, P.; Taylor, P.; Carry, B.; Jacobson, S.

    In the past decade, the number of known binary near-Earth asteroids has more than quadrupled and the number of known large main-belt asteroids with satellites has doubled. Half a dozen triple asteroids have been discovered, and the previously unrecognized populations of asteroid pairs and small main-belt binaries have been identified. The current observational evidence confirms that small (≲20 km) binaries form by rotational fission and establishes that the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect powers the spin-up process. A unifying paradigm based on rotational fission and post-fission dynamics can explain the formation of small binaries, triples, and pairs. Large (>~20 km) binaries with small satellites are most likely created during large collisions.

  4. Females use self-referent cues to avoid mating with previous mates.

    PubMed

    Ivy, Tracie M; Weddle, Carie B; Sakaluk, Scott K

    2005-12-07

    Females of many species mate repeatedly throughout their lives, often with many different males (polyandry). Females can secure genetic benefits by maximizing their diversity of mating partners, and might be expected, therefore, to forego matings with previous partners in favour of novel males. Indeed, a female preference for novel mating partners has been shown in several taxa, but the mechanism by which females distinguish between novel males and previous mates remains unknown. We show that female crickets (Gryllodes sigillatus) mark males with their own unique chemical signatures during mating, enabling females to recognize prior mates in subsequent encounters and to avoid remating with them. Because self-referent chemosensory cues provide females with a simple, but reliable mechanism of identifying individuals with whom they have mated without requiring any special cognitive ability, they may be a widespread means by which females across a broad range of animal mating systems maximize the genetic benefits of polyandry.

  5. Females use self-referent cues to avoid mating with previous mates

    PubMed Central

    Ivy, Tracie M; Weddle, Carie B; Sakaluk, Scott K

    2005-01-01

    Females of many species mate repeatedly throughout their lives, often with many different males (polyandry). Females can secure genetic benefits by maximizing their diversity of mating partners, and might be expected, therefore, to forego matings with previous partners in favour of novel males. Indeed, a female preference for novel mating partners has been shown in several taxa, but the mechanism by which females distinguish between novel males and previous mates remains unknown. We show that female crickets (Gryllodes sigillatus) mark males with their own unique chemical signatures during mating, enabling females to recognize prior mates in subsequent encounters and to avoid remating with them. Because self-referent chemosensory cues provide females with a simple, but reliable mechanism of identifying individuals with whom they have mated without requiring any special cognitive ability, they may be a widespread means by which females across a broad range of animal mating systems maximize the genetic benefits of polyandry. PMID:16271971

  6. Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence.

    PubMed

    Davies, Bryan W; Bogard, Ryan W; Young, Travis S; Mekalanos, John J

    2012-04-13

    The function of the Vibrio 7(th) pandemic island-1 (VSP-1) in cholera pathogenesis has remained obscure. Utilizing chromatin immunoprecipitation sequencing and RNA sequencing to map the regulon of the master virulence regulator ToxT, we identify a TCP island-encoded small RNA that reduces the expression of a previously unrecognized VSP-1-encoded transcription factor termed VspR. VspR modulates the expression of several VSP-1 genes including one that encodes a novel class of di-nucleotide cyclase (DncV), which preferentially synthesizes a previously undescribed hybrid cyclic AMP-GMP molecule. We show that DncV is required for efficient intestinal colonization and downregulates V. cholerae chemotaxis, a phenotype previously associated with hyperinfectivity. This pathway couples the actions of previously disparate genomic islands, defines VSP-1 as a pathogenicity island in V. cholerae, and implicates its occurrence in 7(th) pandemic strains as a benefit for host adaptation through the production of a regulatory cyclic di-nucleotide. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Pelvic Inlet Shape Is Not as Dimorphic as Previously Suggested.

    PubMed

    Delprete, Hillary

    2017-04-01

    It is well known that there are significant differences in the pelves of males and females due, in part, to differing constraints. The male and female pelves must be suitable for upright posture and locomotion, but the female pelvis must also be suitable for reproduction. These differing requirements lead to differences in the shape and size of various pelvic dimensions. These differences are reflected in the pelvic inlet, midplane, and outlet. Current research has documented dimorphisms in the posterior and anterior spaces in all three of these planes. One measure however, that is calculated from the relationship between the length of the anterior-posterior diameter (APD) and the transverse diameter (TD) of the inlet, is not as dimorphic as previously suggested. This computed value is used to describe four main categories of inlet shape: android, gynecoid, anthropoid, and platypelloid. Current textbooks in anatomy and midwifery describe these forms and identify the typical male inlet shape as android and the typical female inlet shape as gynecoid. In this study, however, using skeletonized pelves of 378 adult individuals from three identified skeletal collections, the most common inlet shape for both males and females was android. In addition, when examining shape as a continuous variable, inlet shape is not sexually dimorphic in two of the three populations examined in this study. Based on the results of this study, the inlet shape for males and females is less dimorphic than previously thought, and we need to discontinue using pelvic categories to describe typical inlet shape. Anat Rec, 300:706-715, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Milankovitch wobble?

    NASA Astrophysics Data System (ADS)

    Mitchell, R. N.; Thissen, C.; Kirschvink, J. L.; Schrag, D. P.; Montanari, A.; Coccioni, R.; Slotznick, S. P.; Yamazaki, T.; Penserini, B. D.; Abrahams, J. N. H.; Cruz-Heredia, M.; Evans, D. A.

    2015-12-01

    High-resolution paleomagnetism of Cretaceous-aged limestone in Italy reveals evidence for a previously unrecognized ~10˚ directional variation, or "wobble", of either the geographic or magnetic pole on a 106-year, "Milankovitch" time scale. Ten ~1 million year (Myr) wobbles of magnetic inclination can be identified and correlated across Italy from 87-74 Myr ago, potentially refining the global polarity time scale and seafloor spreading rates. Milankovitch wobble is an omnipresent geophysical process that represents, irrespective of its mechanism, a new chronometer for age calibration with paleomagnetism. If Milankovitch wobble is interpreted as a geomagnetic artifact—the long-considered but still unproven idea that astronomical variations influence the geodynamo—the geocentric-axial dipole hypothesis would only be viable when averaged over time scales 100 times greater than currently thought, making present-day geocentricity largely coincidental. If interpreted as true geographic change, Milankovitch wobble implies an unrecognized, rapid time scale (~10˚ Myr-1) of true polar wander, possibly due to ice sheet dynamics driven by the 1.2 Myr modulation of Earth's rotational obliquity. Stable isotope data co-vary with the Milankovitch wobble, possibly favoring the polar wander mechanism that predicts rapid environmental change where the geomagnetic artifact hypothesis does not.

  9. The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity.

    PubMed

    Reznikov, Leah R; Meyerholz, David K; Abou Alaiwa, Mahmoud H; Kuan, Shin-Ping; Liao, Yan-Shin J; Bormann, Nicholas L; Bair, Thomas B; Price, Margaret; Stoltz, David A; Welsh, Michael J

    2018-04-05

    Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity. As a comparison, we also utilized previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating airway hyperreactivity; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.

  10. A Locus Encoding Variable Defense Systems against Invading DNA Identified in Streptococcus suis

    PubMed Central

    Okura, Masatoshi; Nozawa, Takashi; Watanabe, Takayasu; Murase, Kazunori; Nakagawa, Ichiro; Takamatsu, Daisuke; Osaki, Makoto; Sekizaki, Tsutomu; Gottschalk, Marcelo; Hamada, Shigeyuki

    2017-01-01

    Streptococcus suis, an important zoonotic pathogen, is known to have an open pan-genome and to develop a competent state. In S. suis, limited genetic lineages are suggested to be associated with zoonosis. However, little is known about the evolution of diversified lineages and their respective phenotypic or ecological characteristics. In this study, we performed comparative genome analyses of S. suis, with a focus on the competence genes, mobile genetic elements, and genetic elements related to various defense systems against exogenous DNAs (defense elements) that are associated with gene gain/loss/exchange mediated by horizontal DNA movements and their restrictions. Our genome analyses revealed a conserved competence-inducing peptide type (pherotype) of the competence system and large-scale genome rearrangements in certain clusters based on the genome phylogeny of 58 S. suis strains. Moreover, the profiles of the defense elements were similar or identical to each other among the strains belonging to the same genomic clusters. Our findings suggest that these genetic characteristics of each cluster might exert specific effects on the phenotypic or ecological differences between the clusters. We also found certain loci that shift several types of defense elements in S. suis. Of note, one of these loci is a previously unrecognized variable region in bacteria, at which strains of distinct clusters code for different and various defense elements. This locus might represent a novel defense mechanism that has evolved through an arms race between bacteria and invading DNAs, mediated by mobile genetic elements and genetic competence. PMID:28379509

  11. Bilateral pheochromocytoma during the postpartum period.

    PubMed

    Wattanachanya, Lalita; Bunworasate, Udomsak; Plengpanich, Wanee; Houngngam, Natnicha; Buranasupkajorn, Patinut; Sunthornyothin, Sarat; Shotelersuk, Vorasuk; Snabboon, Thiti

    2009-12-01

    Pheochromocytoma manifesting during pregnancy is uncommon but it is responsible for a high maternal and fetal mortality rate, especially when unrecognized. Most cases of pheochromocytoma are sporadic but they can be part of hereditary autosomal dominant syndromes. We describe a case of bilateral pheochromocytoma in a term-pregnant patient with a previous history of medullary thyroid carcinoma (MTC). Her genetic study revealed a heterozygous mutation, c.1900T>C, in the RET proto-oncogene which confirmed the diagnosis of multiple endocrine neoplasia type 2A (MEN2A). Unrecognized, the tumors caused a crisis with fatal outcome in the mother during the postpartum period. This event might have been prevented if the tumor had been detected previously. MEN2A affected pregnancy is an unusual condition. This syndrome should be suspected when a pregnant patient has a history of MTC. Early detection and appropriate management can prevent serious maternal and fetal complications. We also reviewed the literature of MEN2A-affected pregnancies.

  12. A Cryo-Electron Microscopy Study Identifies the Complete H16.V5 Epitope and Reveals Global Conformational Changes Initiated by Binding of the Neutralizing Antibody Fragment

    PubMed Central

    Lee, Hyunwook; Brendle, Sarah A.; Bywaters, Stephanie M.; Guan, Jian; Ashley, Robert E.; Yoder, Joshua D.; Makhov, Alexander M.; Conway, James F.; Christensen, Neil D.

    2014-01-01

    ABSTRACT Human papillomavirus 16 (HPV16) is a worldwide health threat and an etiologic agent of cervical cancer. To understand the antigenic properties of HPV16, we pursued a structural study to elucidate HPV capsids and antibody interactions. The cryo-electron microscopy (cryo-EM) structures of a mature HPV16 particle and an altered capsid particle were solved individually and as complexes with fragment of antibody (Fab) from the neutralizing antibody H16.V5. Fitted crystal structures provided a pseudoatomic model of the virus-Fab complex, which identified a precise footprint of H16.V5, including previously unrecognized residues. The altered-capsid–Fab complex map showed that binding of the Fab induced significant conformational changes that were not seen in the altered-capsid structure alone. These changes included more ordered surface loops, consolidated so-called “invading-arm” structures, and tighter intercapsomeric connections at the capsid floor. The H16.V5 Fab preferentially bound hexavalent capsomers likely with a stabilizing effect that directly correlated with the number of bound Fabs. Additional cryo-EM reconstructions of the virus-Fab complex for different incubation times and structural analysis provide a model for a hyperstabilization of the capsomer by H16.V5 Fab and showed that the Fab distinguishes subtle differences between antigenic sites. IMPORTANCE Our analysis of the cryo-EM reconstructions of the HPV16 capsids and virus-Fab complexes has identified the entire HPV.V5 conformational epitope and demonstrated a detailed neutralization mechanism of this clinically important monoclonal antibody against HPV16. The Fab bound and ordered the apical loops of HPV16. This conformational change was transmitted to the lower region of the capsomer, resulting in enhanced intercapsomeric interactions evidenced by the more ordered capsid floor and “invading-arm” structures. This study advances the understanding of the neutralization mechanism used

  13. Association between previous splenectomy and gastric dilatation-volvulus in dogs: 453 cases (2004-2009).

    PubMed

    Sartor, Angela J; Bentley, Adrienne M; Brown, Dorothy C

    2013-05-15

    To evaluate the association between previous splenectomy and gastric dilatation-volvulus (GDV) in dogs. Multi-institutional retrospective case-control study. Animals-151 dogs treated surgically for GDV and 302 control dogs with no history of GDV. Computerized records of dogs evaluated via exploratory laparotomy or abdominal ultrasonography were searched, and dogs with GDV and dogs without GDV (control dogs) were identified. Two control dogs were matched with respect to age, body weight, sex, neuter status, and breed to each dog with GDV. Data were collected on the presence or absence of the spleen for both dogs with GDV and control dogs. Conditional logistic regression analysis was used to investigate the association of previous splenectomy with GDV. 6 (4%) dogs in the GDV group and 3 (1%) dogs in the control group had a history of previous splenectomy. The odds of GDV in dogs with a history of previous splenectomy in this population of dogs were 5.3 times those of dogs without a history of previous splenectomy (95% confidence interval, 1.1 to 26.8). For the patients in the present study, there was an increased odds of GDV in dogs with a history of splenectomy. Prophylactic gastropexy may be considered in dogs undergoing a splenectomy, particularly if other risk factors for GDV are present.

  14. Interactome analyses identify ties of PrP and its mammalian paralogs to oligomannosidic N-glycans and endoplasmic reticulum-derived chaperones.

    PubMed

    Watts, Joel C; Huo, Hairu; Bai, Yu; Ehsani, Sepehr; Jeon, Amy Hye Won; Won, Amy Hye; Shi, Tujin; Daude, Nathalie; Lau, Agnes; Young, Rebecca; Xu, Lei; Carlson, George A; Williams, David; Westaway, David; Schmitt-Ulms, Gerold

    2009-10-01

    The physiological environment which hosts the conformational conversion of the cellular prion protein (PrP(C)) to disease-associated isoforms has remained enigmatic. A quantitative investigation of the PrP(C) interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the study was extended to Doppel (Prnd) and Shadoo (Sprn), two mammalian PrP(C) paralogs. Interestingly, this work not only established a similar physiological environment for the three prion protein family members in neuroblastoma cells, but also suggested direct interactions amongst them. Furthermore, multiple interactions between PrP(C) and the neural cell adhesion molecule, the laminin receptor precursor, Na/K ATPases and protein disulfide isomerases (PDI) were confirmed, thereby reconciling previously separate findings. Subsequent validation experiments established that interactions of PrP(C) with PDIs may extend beyond the endoplasmic reticulum and may play a hitherto unrecognized role in the accumulation of PrP(Sc). A simple hypothesis is presented which accounts for the majority of interactions observed in uninfected cells and suggests that PrP(C) organizes its molecular environment on account of its ability to bind to adhesion molecules harboring immunoglobulin-like domains, which in turn recognize oligomannose-bearing membrane proteins.

  15. Consistent negative temperature sensitivity and positive influence of precipitation on growth of floodplain Picea glauca in Interior Alaska

    Treesearch

    Glenn Patrick Juday; Claire. Alix

    2012-01-01

    This paper calibrates climate controls over radial growth of floodplain white spruce (Picea glauca (Moench) Voss) and examines whether growth in these populations responds similarly to climate as upland trees in Interior Alaska. Floodplain white spruce trees hold previously unrecognized potential for long-term climate reconstruction because they...

  16. Using a Critical Reflection Framework and Collaborative Inquiry to Improve Teaching Practice: An Action Research Project

    ERIC Educational Resources Information Center

    Briscoe, Patricia

    2017-01-01

    This action research reports on a three-year collaborative learning process among three teachers. We used current literature and a critical reflection framework to understand why our teaching approaches were not resulting in increased student learning. This allowed us to examine our previously unrecognized and uninterrupted--and often,…

  17. Plantar pressure and daily cumulative stress in persons affected by leprosy with current, previous and no previous foot ulceration.

    PubMed

    van Schie, Carine H M; Slim, Frederik J; Keukenkamp, Renske; Faber, William R; Nollet, Frans

    2013-03-01

    Not only plantar pressure but also weight-bearing activity affects accumulated mechanical stress to the foot and may be related to foot ulceration. To date, activity has not been accounted for in leprosy. The purpose was to compare barefoot pressure, in-shoe pressure and daily cumulative stress between persons affected by leprosy with and without previous or current foot ulceration. Nine persons with current plantar ulceration were compared to 15 with previous and 15 without previous ulceration. Barefoot peak pressure (EMED-X), in-shoe peak pressure (Pedar-X) and daily cumulative stress (in-shoe forefoot pressure time integral×mean daily strides (Stepwatch™ Activity Monitor)) were measured. Barefoot peak pressure was increased in persons with current and previous compared to no previous foot ulceration (mean±SD=888±222 and 763±335 vs 465±262kPa, p<0.05). In-shoe peak pressure was only increased in persons with current compared to without previous ulceration (mean±SD=412±145 vs 269±70kPa, p<0.05). Daily cumulative stress was not different between groups, although persons with current and previous foot ulceration were less active. Although barefoot peak pressure was increased in people with current and previous plantar ulceration, it did not discriminate between these groups. While in-shoe peak pressure was increased in persons with current ulceration, they were less active, resulting in no difference in daily cumulative stress. Increased in-shoe peak pressure suggests insufficient pressure reducing footwear in persons with current ulceration, highlighting the importance of pressure reducing qualities of footwear. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. ANCA-associated vasculitis in Hispanic Americans: an unrecognized severity.

    PubMed

    Sreih, Antoine G; Mandhadi, Ranadeep; Aldaghlawi, Fadi; Khan, Asad; Irshad, Vajiha; Finn, Katherine; Block, Joel A

    2015-05-01

    This study aims to compare the severity and outcomes of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) between Hispanics and Caucasians living in the same geographical area. All patients diagnosed with AAV at two academic institutions in Chicago from January 2006 to December 2012 were retrospectively and prospectively identified. Disease activity was measured with the Birmingham Vasculitis Activity Score (BVAS), and disease damage was measured with the Vasculitis Damage Index (VDI). Student's t test and chi-square tests were employed; p ≤ 0.05 was considered significant. Seventy patients with AAV were identified; 15 patients were excluded. Fifty-five patients were included in the study: 23 Hispanics and 32 Caucasians, 35 patients with granulomatosis with polyangiitis (Wegener's), 12 with microscopic polyangiitis, 7 with eosinophilic granulomatosis with polyangiitis, and 1 with renal-limited vasculitis. Compared to Caucasians, Hispanics had a higher BVAS at presentation (16.3 ± 7.6 versus 10.7 ± 7.5, p = 0.006), a higher VDI at presentation (2.90 ± 1.50 versus 2.06 ± 1.30, p = 0.030), and a cumulative VDI (3.90 ± 1.70 versus 2.50 ± 1.90, p = 0.010). Renal involvement was more common among Hispanics (85 % of Hispanics versus 48 % of Caucasians, p = 0.01). Seventy percent of Hispanics had acute renal failure (mean creatinine = 3.37 ± 4.4 mg/dl) of whom seven (50 %) required dialysis, versus 25 % of Caucasians (mean creatinine = 1.78 ± 1.57 mg/dl, p = 0.03) and only two requiring dialysis. Compared to Caucasians, Hispanics with AAV present with more severe disease and higher damage indices. Larger studies are required to confirm these findings and delineate the respective roles of environment and genetics in the pathogenesis of the disease.

  19. Comparative genomics of grass EST libraries reveals previously uncharacterized splicing events in crop plants.

    PubMed

    Chuang, Trees-Juen; Yang, Min-Yu; Lin, Chuang-Chieh; Hsieh, Ping-Hung; Hung, Li-Yuan

    2015-02-05

    Crop plants such as rice, maize and sorghum play economically-important roles as main sources of food, fuel, and animal feed. However, current genome annotations of crop plants still suffer false-positive predictions; a more comprehensive registry of alternative splicing (AS) events is also in demand. Comparative genomics of crop plants is largely unexplored. We performed a large-scale comparative analysis (ExonFinder) of the expressed sequence tag (EST) library from nine grass plants against three crop genomes (rice, maize, and sorghum) and identified 2,879 previously-unannotated exons (i.e., novel exons) in the three crops. We validated 81% of the tested exons by RT-PCR-sequencing, supporting the effectiveness of our in silico strategy. Evolutionary analysis reveals that the novel exons, comparing with their flanking annotated ones, are generally under weaker selection pressure at the protein level, but under stronger pressure at the RNA level, suggesting that most of the novel exons also represent novel alternatively spliced variants (ASVs). However, we also observed the consistency of evolutionary rates between certain novel exons and their flanking exons, which provided further evidence of their co-occurrence in the transcripts, suggesting that previously-annotated isoforms might be subject to erroneous predictions. Our validation showed that 54% of the tested genes expressed the newly-identified isoforms that contained the novel exons, rather than the previously-annotated isoforms that excluded them. The consistent results were steadily observed across cultivated (Oryza sativa and O. glaberrima) and wild (O. rufipogon and O. nivara) rice species, asserting the necessity of our curation of the crop genome annotations. Our comparative analyses also inferred the common ancestral transcriptome of grass plants and gain- and loss-of-ASV events. We have reannotated the rice, maize, and sorghum genomes, and showed that evolutionary rates might serve as an indicator

  20. Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol.

    PubMed

    Meric-Bernstam, F; Brusco, L; Daniels, M; Wathoo, C; Bailey, A M; Strong, L; Shaw, K; Lu, K; Qi, Y; Zhao, H; Lara-Guerra, H; Litton, J; Arun, B; Eterovic, A K; Aytac, U; Routbort, M; Subbiah, V; Janku, F; Davies, M A; Kopetz, S; Mendelsohn, J; Mills, G B; Chen, K

    2016-05-01

    Next-generation sequencing in cancer research may reveal germline variants of clinical significance. We report patient preferences for return of results and the prevalence of incidental pathogenic germline variants (PGVs). Targeted exome sequencing of 202 genes was carried out in 1000 advanced cancers using tumor and normal DNA in a research laboratory. Pathogenic variants in 18 genes, recommended for return by The American College of Medical Genetics and Genomics, as well as PALB2, were considered actionable. Patient preferences of return of incidental germline results were collected. Return of results was initiated with genetic counseling and repeat CLIA testing. Of the 1000 patients who underwent sequencing, 43 had likely PGVs: APC (1), BRCA1 (11), BRCA2 (10), TP53 (10), MSH2 (1), MSH6 (4), PALB2 (2), PTEN (2), TSC2 (1), and RB1 (1). Twenty (47%) of 43 variants were previously known based on clinical genetic testing. Of the 1167 patients who consented for a germline testing protocol, 1157 (99%) desired to be informed of incidental results. Twenty-three previously unrecognized mutations identified in the research environment were confirmed with an orthogonal CLIA platform. All patients approached decided to proceed with formal genetic counseling; in all cases where formal genetic testing was carried out, the germline variant of concern validated with clinical genetic testing. In this series, 2.3% patients had previously unrecognized pathogenic germline mutations in 19 cancer-related genes. Thus, genomic sequencing must be accompanied by a plan for return of germline results, in partnership with genetic counseling. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. Nocturnal Hypoglycemia Identified by a Continuous Glucose Monitoring System in Patients with Primary Adrenal Insufficiency (Addison's Disease)

    PubMed Central

    Hackemann, Annika; Reusch, Juergen; Badenhoop, Klaus

    2012-01-01

    Abstract Background Hypoglycemia can be a symptom in patients with Addison's disease. The common regimen of replacement therapy with oral glucocorticoids results in unphysiological low cortisol levels in the early morning, the time of highest insulin sensitivity. Therefore patients with Addison's disease are at risk for unrecognized and potentially severe nocturnal hypoglycemia also because of a disturbed counterregulatory function. Use of a continuous glucose monitoring system (CGMS) could help to adjust hydrocortisone treatment and to avoid nocturnal hypoglycemia in these patients. Methods Thirteen patients with Addison's disease were screened for hypoglycemia wearing a CGMS for 3–5 days. Results In one patient we identified a hypoglycemic episode at 3:45 a.m. with a blood glucose level of 46 mg/dL, clearly beneath the 95% tolerance interval of minimal glucose levels between 2 and 4 a.m. (53.84 mg/dL). After the hydrocortisone replacement scheme was changed, the minimum blood glucose level between 2 and 4 a.m. normalized to 87 mg/dL. Conclusions Continuous glucose monitoring can detect nocturnal hypoglycemia in patients with primary adrenal insufficiency and hence prevent in these patients an impaired quality of life and even serious adverse effects. PMID:22242902

  2. Edge-Region Grouping in Figure-Ground Organization and Depth Perception

    ERIC Educational Resources Information Center

    Palmer, Stephen E.; Brooks, Joseph L.

    2008-01-01

    Edge-region grouping (ERG) is proposed as a unifying and previously unrecognized class of relational information that influences figure-ground organization and perceived depth across an edge. ERG occurs when the edge between two regions is differentially grouped with one region based on classic principles of similarity grouping. The ERG hypothesis…

  3. Portable Diagnostic Devices for Identifying Obstructive Sleep Apnea among Commercial Motor Vehicle Drivers: Considerations and Unanswered Questions

    PubMed Central

    Zhang, Chunbai; Berger, Mark; Malhotra, Atul; Kales, Stefanos N.

    2012-01-01

    Obstructive sleep apnea (OSA), a syndrome defined by breathing abnormalities during sleep, can lead to fatigue and excessive daytime sleepiness (EDS) with an increased risk of motor vehicle crashes. Identifying commercial motor vehicle operators with unrecognized OSA is a major public health priority. Portable monitors (PMs) are being actively marketed to trucking firms as potentially lower-cost and more accessible alternatives to the reference standard of in-laboratory polysomnography (PSG) in the diagnosis of OSA among commercial motor vehicle operators. Several factors regarding PMs remain uncertain in this unique patient population: their sensitivity and specificity; the cost-benefit ratio of the PMs versus PSG; potential barriers from human factors; and evolving technologic advancement. Human factors that alter test accuracy are a major concern among commercial drivers motivated to gain/maintain employment. Current available data using PMs as a diagnostic tool among CMV operators indicate relatively high data loss and high loss to follow-up. Loss to follow-up has also been an issue using PSG in commercial motor vehicle operators. Furthermore, PM testing and PM results interpretation protocols may have no sleep specialist oversight, and sometimes minimal physician oversight and involvement. Additional studies comparing unattended and unmonitored PMs directly against full in-laboratory PSG are needed to provide evidence for their efficacy among commercial motor vehicle operators. Citation: Zhang C; Berger M; Malhotra A; Kales SN. Portable diagnostic devices for identifying obstructive sleep apnea among commercial motor vehicle drivers: considerations and unanswered questions. SLEEP 2012;35(11):1481-1489. PMID:23115397

  4. Identification and pathway analysis of microRNAs with no previous involvement in breast cancer.

    PubMed

    Romero-Cordoba, Sandra; Rodriguez-Cuevas, Sergio; Rebollar-Vega, Rosa; Quintanar-Jurado, Valeria; Maffuz-Aziz, Antonio; Jimenez-Sanchez, Gerardo; Bautista-Piña, Veronica; Arellano-Llamas, Rocio; Hidalgo-Miranda, Alfredo

    2012-01-01

    microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described.

  5. Male songbirds provide indirect parental care by guarding females during incubation

    USGS Publications Warehouse

    Fedy, B.C.; Martin, T.E.

    2009-01-01

    Across many taxa, guarding of fertile mates is a widespread tactic that enhances paternity assurance. However, guarding of mates can also occur during the nonfertile period, and the fitness benefits of this behavior are unclear. Male songbirds, for example, sometimes guard nonfertile females during foraging recesses from incubation. We hypothesized that guarding postreproductive mates may have important, but unrecognized, benefits by enhancing female foraging efficiency, thereby increasing time spent incubating eggs. We tested the hypothesis in 2 songbird species by examining female behavior during natural and experimentally induced absences of males. Male absence caused increased vigilance in foraging females that decreased their efficiency and resulted in less time spent incubating eggs. Male guarding of nonfertile females can thus provide a previously unrecognized form of indirect parental care.

  6. A previously unrecognized path of early Holocene base flow and elevated discharge from Lake Minong to Lake Chippewa across eastern Upper Michigan

    USGS Publications Warehouse

    Loope, Walter L.; Jol, Harry M.; Fisher, Timothy G.; Blewett, William L.; Loope, Henry M.; Legg, Robert J.

    2014-01-01

    It has long been hypothesized that flux of fresh meltwater from glacial Lake Minong in North America's Superior Basin to the North Atlantic Ocean triggered rapid climatic shifts during the early Holocene. The spatial context of recent support for this idea demands a reevaluation of the exit point of meltwater from the Superior Basin. We used ground penetrating radar (GPR), foundation borings from six highway bridges, a GIS model of surface topography, geologic maps, U.S. Department of Agriculture–Natural Resources Conservation Service soils maps, and well logs to investigate the possible linkage of Lake Minong with Lake Chippewa in the Lake Michigan Basin across eastern Upper Michigan. GPR suggests that a connecting channel lies buried beneath the present interlake divide at Danaher. A single optical age hints that the channel aggraded to 225 m as elevated receipt of Lake Agassiz meltwater in the Superior Basin began to wane <10.6 ka. The large supply of sediment required to accommodate aggradation was immediately available at the channel's edge in the littoral shelves of abandoned Lake Algonquin and in distal parts of post-Algonquin fans. As discharge decreased further, the aggraded channel floor was quickly breached and interbasin flow to Lake Chippewa was restored. Basal radiocarbon ages on wood from small lakes along the discharge path and a GIS model of Minong's shoreline are consistent with another transgression of Minong after ca. 9.5 ka. At the peak of the latter transgression, the southeastern rim of the Superior Basin (Nadoway Drift Barrier) failed, ending Lake Minong. Upon Minong's final drop, aggradational sediments were deposited at Danaher, infilling the prior breach.

  7. Gemfibrozil markedly increases the plasma concentrations of montelukast: a previously unrecognized role for CYP2C8 in the metabolism of montelukast.

    PubMed

    Karonen, T; Filppula, A; Laitila, J; Niemi, M; Neuvonen, P J; Backman, J T

    2010-08-01

    According to available information, montelukast is metabolized by cytochrome P450 (CYP) 3A4 and 2C9. In order to study the significance of CYP2C8 in the pharmacokinetics of montelukast, 10 healthy subjects were administered gemfibrozil 600 mg or placebo twice daily for 3 days, and 10 mg montelukast on day 3, in a randomized, crossover study. Gemfibrozil increased the mean area under the plasma concentration-time curve (AUC)(0-infinity), peak plasma concentration (C(max)), and elimination half-life (t(1/2)) of montelukast 4.5-fold, 1.5-fold, and 3.0-fold, respectively (P < 0.001). After administration of gemfibrozil, the time to reach C(max) (t(max)) of the montelukast metabolite M6 was prolonged threefold (P = 0.005), its AUC(0-7) was reduced by 40% (P = 0.027), and the AUC(0-24) of the secondary metabolite M4 was reduced by >90% (P < 0.001). In human liver microsomes, gemfibrozil 1-O-beta glucuronide inhibited the formation of M6 (but not of M5) from montelukast 35-fold more potently than did gemfibrozil (half-maximal inhibitory concentration (IC(50)) 3.0 and 107 micromol/l, respectively). In conclusion, gemfibrozil markedly increases the plasma concentrations of montelukast, indicating that CYP2C8 is crucial in the elimination of montelukast.

  8. Blood pressure loci identified with a gene-centric array.

    PubMed

    Johnson, Toby; Gaunt, Tom R; Newhouse, Stephen J; Padmanabhan, Sandosh; Tomaszewski, Maciej; Kumari, Meena; Morris, Richard W; Tzoulaki, Ioanna; O'Brien, Eoin T; Poulter, Neil R; Sever, Peter; Shields, Denis C; Thom, Simon; Wannamethee, Sasiwarang G; Whincup, Peter H; Brown, Morris J; Connell, John M; Dobson, Richard J; Howard, Philip J; Mein, Charles A; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Davey Smith, George; Day, Ian N M; Lawlor, Debbie A; Goodall, Alison H; Fowkes, F Gerald; Abecasis, Gonçalo R; Elliott, Paul; Gateva, Vesela; Braund, Peter S; Burton, Paul R; Nelson, Christopher P; Tobin, Martin D; van der Harst, Pim; Glorioso, Nicola; Neuvrith, Hani; Salvi, Erika; Staessen, Jan A; Stucchi, Andrea; Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-François; Tichet, Jean; Juhanson, Peeter; Org, Elin; Putku, Margus; Sõber, Siim; Veldre, Gudrun; Viigimaa, Margus; Levinsson, Anna; Rosengren, Annika; Thelle, Dag S; Hastie, Claire E; Hedner, Thomas; Lee, Wai K; Melander, Olle; Wahlstrand, Björn; Hardy, Rebecca; Wong, Andrew; Cooper, Jackie A; Palmen, Jutta; Chen, Li; Stewart, Alexandre F R; Wells, George A; Westra, Harm-Jan; Wolfs, Marcel G M; Clarke, Robert; Franzosi, Maria Grazia; Goel, Anuj; Hamsten, Anders; Lathrop, Mark; Peden, John F; Seedorf, Udo; Watkins, Hugh; Ouwehand, Willem H; Sambrook, Jennifer; Stephens, Jonathan; Casas, Juan-Pablo; Drenos, Fotios; Holmes, Michael V; Kivimaki, Mika; Shah, Sonia; Shah, Tina; Talmud, Philippa J; Whittaker, John; Wallace, Chris; Delles, Christian; Laan, Maris; Kuh, Diana; Humphries, Steve E; Nyberg, Fredrik; Cusi, Daniele; Roberts, Robert; Newton-Cheh, Christopher; Franke, Lude; Stanton, Alice V; Dominiczak, Anna F; Farrall, Martin; Hingorani, Aroon D; Samani, Nilesh J; Caulfield, Mark J; Munroe, Patricia B

    2011-12-09

    Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. The frequency of previously undetectable deletions involving 3' Exons of the PMS2 gene.

    PubMed

    Vaughn, Cecily P; Baker, Christine L; Samowitz, Wade S; Swensen, Jeffrey J

    2013-01-01

    Lynch syndrome is characterized by mutations in one of four mismatch repair genes, MLH1, MSH2, MSH6, or PMS2. Clinical mutation analysis of these genes includes sequencing of exonic regions and deletion/duplication analysis. However, detection of deletions and duplications in PMS2 has previously been confined to Exons 1-11 due to gene conversion between PMS2 and the pseudogene PMS2CL in the remaining 3' exons (Exons 12-15). We have recently described an MLPA-based method that permits detection of deletions of PMS2 Exons 12-15; however, the frequency of such deletions has not yet been determined. To address this question, we tested for 3' deletions in 58 samples that were reported to be negative for PMS2 mutations using previously available methods. All samples were from individuals whose tumors exhibited loss of PMS2 immunohistochemical staining without concomitant loss of MLH1 immunostaining. We identified seven samples in this cohort with deletions in the 3' region of PMS2, including three previously reported samples with deletions of Exons 13-15 (two samples) and Exons 14-15. Also detected were deletions of Exons 12-15, Exon 13, and Exon 14 (two samples). Breakpoint analysis of the intragenic deletions suggests they occurred through Alu-mediated recombination. Our results indicate that ∼12% of samples suspected of harboring a PMS2 mutation based on immunohistochemical staining, for which mutations have not yet been identified, would benefit from testing using the new methodology. Copyright © 2012 Wiley Periodicals, Inc.

  10. Neurological syndromes driven by postinfectious processes or unrecognized persistent infections.

    PubMed

    Johnson, Tory P; Nath, Avindra

    2018-06-01

    The immune system serves a critical role in protecting the host against various pathogens. However, under circumstances, once triggered by the infectious process, it may be detrimental to the host. This may be as a result of nonspecific immune activation or due to a targeted immune response to a specific host antigen. In this opinion piece, we discuss the underlying mechanisms that lead to such an inflammatory or autoimmune syndrome affecting the nervous system. We examine these hypotheses in the context of recent emerging infections to provide mechanistic insight into the clinical manifestations and rationale for immunomodulatory therapy. Some pathogens endure longer than previously thought. Persistent infections may continue to drive immune responses resulting in chronic inflammation or development of autoimmune processes, resulting in damage to the nervous system. Patients with genetic susceptibilities in immune regulation may be particularly vulnerable to pathogen driven autoimmune responses. The presence of prolonged pathogens may result in chronic immune stimulations that drives immune-mediated neurologic complications. Understanding the burden and mechanisms of these processes is challenging but important.

  11. Degradation of curcumin: From mechanism to biological implications

    PubMed Central

    Schneider, Claus; Gordon, Odaine N.; Edwards, Rebecca L.; Luis, Paula B.

    2016-01-01

    Curcumin is the main bioactive ingredient in turmeric extract and widely consumed as part of the spice mix curry or as dietary supplement. Turmeric has a long history of therapeutic application in traditional Asian medicine. Biomedical studies conducted in the past two decades have identified a large number of cellular targets and effects of curcumin. In vitro curcumin rapidly degrades in an autoxidative transformation to diverse chemical species, formation of which has only recently been appreciated. We discuss how degradation and metabolism of curcumin, through products and their mechanism of formation, provide a basis for the interpretation of preclinical data and clinical studies. We suggest that the previously unrecognized diversity of its degradation products could be an important factor in explaining the polypharmacology of curcumin. PMID:25817068

  12. Canonical DNA Repair Pathways Influence R-Loop-Driven Genome Instability.

    PubMed

    Stirling, Peter C; Hieter, Philip

    2017-10-27

    DNA repair defects create cancer predisposition in humans by fostering a higher rate of mutations. While DNA repair is quite well characterized, recent studies have identified previously unrecognized relationships between DNA repair and R-loop-mediated genome instability. R-loops are three-stranded nucleic acid structures in which RNA binds to genomic DNA to displace a loop of single-stranded DNA. Mutations in homologous recombination, nucleotide excision repair, crosslink repair, and DNA damage checkpoints have all now been linked to formation and function of transcription-coupled R-loops. This perspective will summarize recent literature linking DNA repair to R-loop-mediated genomic instability and discuss how R-loops may contribute to mutagenesis in DNA-repair-deficient cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. A New Approach for Identifying Patients with Undiagnosed Chronic Obstructive Pulmonary Disease

    PubMed Central

    Mannino, David; Leidy, Nancy Kline; Malley, Karen G.; Bacci, Elizabeth D.; Barr, R. Graham; Bowler, Russ P.; Han, MeiLan K.; Houfek, Julia F.; Make, Barry; Meldrum, Catherine A.; Rennard, Stephen; Thomashow, Byron; Walsh, John; Yawn, Barbara P.

    2017-01-01

    Rationale: Chronic obstructive pulmonary disease (COPD) is often unrecognized and untreated. Objectives: To develop a method for identifying undiagnosed COPD requiring treatment with currently available therapies (FEV1 <60% predicted and/or exacerbation risk). Methods: We conducted a multisite, cross-sectional, case-control study in U.S. pulmonary and primary care clinics that recruited subjects from primary care settings. Cases were patients with COPD and at least one exacerbation in the past year or FEV1 less than 60% of predicted without exacerbation in the past year. Control subjects were persons with no COPD or with mild COPD (FEV1 ≥60% predicted, no exacerbation in the past year). In random forests analyses, we identified the smallest set of questions plus peak expiratory flow (PEF) with optimal sensitivity (SN) and specificity (SP). Measurements and Main Results: PEF and spirometry were recorded in 186 cases and 160 control subjects. The mean (SD) age of the sample population was 62.7 (10.1) years; 55% were female; 86% were white; and 16% had never smoked. The mean FEV1 percent predicted for cases was 42.5% (14.2%); for control subjects, it was 82.5% (15.7%). A five-item questionnaire, CAPTURE (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk), was used to assess exposure, breathing problems, tiring easily, and acute respiratory illnesses. CAPTURE exhibited an SN of 95.7% and an SP of 44.4% for differentiating cases from all control subjects, and an SN of 95.7% and an SP of 67.8% for differentiating cases from no-COPD control subjects. The PEF (males, <350 L/min; females, <250 L/min) SN and SP were 88.0% and 77.5%, respectively, for differentiating cases from all control subjects, and they were 88.0% and 90.8%, respectively, for distinguishing cases from no-COPD control subjects. The CAPTURE plus PEF exhibited improved SN and SP for all cases versus all control subjects (89.7% and 78.1%, respectively) and

  14. Preseason Perceived Physical Capability and Previous Injury.

    PubMed

    Sciascia, Aaron; Haegele, Lauren E; Lucas, Jean; Uhl, Timothy L

    2015-09-01

    Patient opinion about the ability to perform athletic maneuvers is important after injury; however, prospective assessment of self-perceived physical capability for athletes before the beginning of a season is lacking. To perform a descriptive analysis of knee, shoulder, and elbow self-perceived measures of physical capability specific to athletics and to compare the measures between athletes with and without a history of injury. Cross-sectional study. Preparticipation physical examinations. A total of 738 collegiate athletes (486 men, 251 women; age = 19 ± 1 years) were administered questionnaires after receiving medical clearance to participate in their sports. Of those athletes, 350 reported a history of injury. Athletes self-reported a history of knee, shoulder, or elbow injury. Perceived physical capability of the 3 joints was evaluated using the Knee Injury and Osteoarthritis Outcome Score Sport and Recreation Function and Knee-Related Quality of Life subscales and the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score. We conducted nonparametric analysis to determine if scores differed between athletes with and without a history of injury. Median values for the Knee Injury and Osteoarthritis Outcome Score Sports and Recreation Function and Knee-Related Quality of Life subscales and the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score for all athletes were 100. Median values for perceived physical capability of athletes with a history of injury were 3 to 12 points lower for each questionnaire before the start of the season (P < .001). Our study provided descriptive values for individual perceived knee, shoulder, and elbow physical capability of collegiate athletes participating in 19 sports. Athletes who did not report previous injuries perceived their physical capabilities to be nearly perfect, which could set the goal for these athletes to return to participation after injury. Athletes reporting previous injuries perceived less physical

  15. Protein Supplement Usage Among Male University Students: Comparisons Between Current and Previous Users.

    PubMed

    Sung, Youngmo; Choi, Jinkyung

    2018-02-01

    Interest in specialized dietary supplements is leading market growth, and protein supplements are popular for increasing muscle mass among young males. Therefore, this study investigated the attitudes toward and satisfaction with protein supplements to identify detailed consumer behaviors related to the consumption of protein supplements. The study sample includes male university students in their 20s in South Korea. In total, 223 responses were entered for analysis. Questions related to attitudes, satisfaction, and future behavioral intentions were asked using 5-point Likert scales. The responses were divided into two groups, current and previous users, to identify significant differences in terms of attitudes, satisfaction, and future behavioral intentions. A descriptive analysis, analysis of variance (ANOVA), and multiple regression were run. The majority of respondents prefer the powdered form of supplements in bulk with a price range between 30,000 won and 60,000 won. Online shopping was preferred, while word of mouth and friends/family were considered credible information sources. The most common side effects experienced were problems with digestion and hives, although more than 78% did not experience side effects. In comparison between current and previous users in terms of attitudes and satisfaction, the following areas showed significances. Regarding attitudes, the importance of brand, preference for products from overseas, the search for nutritional facts, and reading carefully all product information were significant, while regarding satisfaction, price, effectiveness, and ease of consumption were significant. All significances showed that current users had more positive attitudes and greater satisfaction. Overall, consumers' satisfaction regarding ease of consumption influenced future behavioral intentions. The market for protein supplements has been growing, so measuring consumers' attitudes and satisfaction would help attract potential consumers. In

  16. KRAS as a Therapeutic Target.

    PubMed

    McCormick, Frank

    2015-04-15

    KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus. ©2015 American Association for Cancer Research.

  17. Control of jasmonate biosynthesis and senescence by miR319 targets.

    PubMed

    Schommer, Carla; Palatnik, Javier F; Aggarwal, Pooja; Chételat, Aurore; Cubas, Pilar; Farmer, Edward E; Nath, Utpal; Weigel, Detlef

    2008-09-23

    Considerable progress has been made in identifying the targets of plant microRNAs, many of which regulate the stability or translation of mRNAs that encode transcription factors involved in development. In most cases, it is unknown, however, which immediate transcriptional targets mediate downstream effects of the microRNA-regulated transcription factors. We identified a new process controlled by the miR319-regulated clade of TCP (TEOSINTE BRANCHED/CYCLOIDEA/PCF) transcription factor genes. In contrast to other miRNA targets, several of which modulate hormone responses, TCPs control biosynthesis of the hormone jasmonic acid. Furthermore, we demonstrate a previously unrecognized effect of TCPs on leaf senescence, a process in which jasmonic acid has been proposed to be a critical regulator. We propose that miR319-controlled TCP transcription factors coordinate two sequential processes in leaf development: leaf growth, which they negatively regulate, and leaf senescence, which they positively regulate.

  18. Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.

    PubMed

    Cowell, Annie N; Istvan, Eva S; Lukens, Amanda K; Gomez-Lorenzo, Maria G; Vanaerschot, Manu; Sakata-Kato, Tomoyo; Flannery, Erika L; Magistrado, Pamela; Owen, Edward; Abraham, Matthew; LaMonte, Gregory; Painter, Heather J; Williams, Roy M; Franco, Virginia; Linares, Maria; Arriaga, Ignacio; Bopp, Selina; Corey, Victoria C; Gnädig, Nina F; Coburn-Flynn, Olivia; Reimer, Christin; Gupta, Purva; Murithi, James M; Moura, Pedro A; Fuchs, Olivia; Sasaki, Erika; Kim, Sang W; Teng, Christine H; Wang, Lawrence T; Akidil, Aslı; Adjalley, Sophie; Willis, Paul A; Siegel, Dionicio; Tanaseichuk, Olga; Zhong, Yang; Zhou, Yingyao; Llinás, Manuel; Ottilie, Sabine; Gamo, Francisco-Javier; Lee, Marcus C S; Goldberg, Daniel E; Fidock, David A; Wirth, Dyann F; Winzeler, Elizabeth A

    2018-01-12

    Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  19. Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

    PubMed Central

    Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

    2017-01-01

    Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

  20. New Hepatitis E Virus Genotype in Camels, the Middle East

    PubMed Central

    Lau, Susanna K.P.; Teng, Jade L.L.; Tsang, Alan K. L.; Joseph, Marina; Wong, Emily Y.M.; Tang, Ying; Sivakumar, Saritha; Xie, Jun; Bai, Ru; Wernery, Renate; Wernery, Ulrich; Yuen, Kwok-Yung

    2014-01-01

    In a molecular epidemiology study of hepatitis E virus (HEV) in dromedaries in Dubai, United Arab Emirates, HEV was detected in fecal samples from 3 camels. Complete genome sequencing of 2 strains showed >20% overall nucleotide difference to known HEVs. Comparative genomic and phylogenetic analyses revealed a previously unrecognized HEV genotype. PMID:24856611

  1. Fatal Metacestode Infection in Bornean Orangutan Caused by Unknown Versteria Species

    PubMed Central

    Gendron-Fitzpatrick, Annette; Deering, Kathleen M.; Wallace, Roberta S.; Clyde, Victoria L.; Lauck, Michael; Rosen, Gail E.; Bennett, Andrew J.; Greiner, Ellis C.; O’Connor, David H.

    2014-01-01

    A captive juvenile Bornean orangutan (Pongo pygmaeus) died from an unknown disseminated parasitic infection. Deep sequencing of DNA from infected tissues, followed by gene-specific PCR and sequencing, revealed a divergent species within the newly proposed genus Versteria (Cestoda: Taeniidae). Versteria may represent a previously unrecognized risk to primate health. PMID:24377497

  2. Repeat immigration: A previously unobserved source of heterogeneity?

    PubMed

    Aradhya, Siddartha; Scott, Kirk; Smith, Christopher D

    2017-07-01

    Register data allow for nuanced analyses of heterogeneities between sub-groups which are not observable in other data sources. One heterogeneity for which register data is particularly useful is in identifying unique migration histories of immigrant populations, a group of interest across disciplines. Years since migration is a commonly used measure of integration in studies seeking to understand the outcomes of immigrants. This study constructs detailed migration histories to test whether misclassified migrations may mask important heterogeneities. In doing so, we identify a previously understudied group of migrants called repeat immigrants, and show that they differ systematically from permanent immigrants. In addition, we quantify the degree to which migration information is misreported in the registers. The analysis is carried out in two steps. First, we estimate income trajectories for repeat immigrants and permanent immigrants to understand the degree to which they differ. Second, we test data validity by cross-referencing migration information with changes in income to determine whether there are inconsistencies indicating misreporting. From the first part of the analysis, the results indicate that repeat immigrants systematically differ from permanent immigrants in terms of income trajectories. Furthermore, income trajectories differ based on the way in which years since migration is calculated. The second part of the analysis suggests that misreported migration events, while present, are negligible. Repeat immigrants differ in terms of income trajectories, and may differ in terms of other outcomes as well. Furthermore, this study underlines that Swedish registers provide a reliable data source to analyze groups which are unidentifiable in other data sources.

  3. Predicting deterioration in previously healthy infants hospitalized with respiratory syncytial virus infection.

    PubMed

    Brooks, A M; McBride, J T; McConnochie, K M; Aviram, M; Long, C; Hall, C B

    1999-09-01

    To estimate the incidence of clinical deterioration leading to intensive care unit transfer in previously healthy infants with respiratory syncytial virus (RSV) infection hospitalized on a general pediatric unit and, to assess the hypothesis that history, physical examination, oximetry, and chest radiographic findings at time of presentation can accurately identify these infants. A virology database was used to identify and determine the disposition of all children previously healthy, full-term infants admitted initially to the general inpatient services at CHaS or Rochester General Hospital, a second University of Rochester teaching hospital, whose clinical deterioration led to transfer to the pediatric intensive care unit (PICU). These infants were matched retrospectively (for year and date of infection, sex, chronologic age, and race) with two hospitalized controls who did not require PICU transfer. Chest radiographic findings, respiratory rate (RR), O(2) saturation, and presence of wheezing at time of presentation to the emergency department (ED) were compared. During the study years, 542 previously healthy, full-term infants were admitted to the general pediatric unit at CHaS with proven RSV infection. Ten (1.8%; 95% confidence interval, 0.9%, 3.4%) were transferred subsequently to the PICU, primarily for close monitoring of progressive respiratory distress. Data for these patients and 7 patients transferred from Rochester General Hospital to the PICU at the CHaS were compared with those for control patients. The mean RR in the ED (63 vs 50), and O(2) saturation in the ED (88% vs 93%) were modestly abnormal in cases compared with controls. Wheezing on examination at time of presentation and chest radiographic findings did not differ between the two groups. A RR >80 and an O(2) saturation <85% at time of

  4. 14 CFR 60.17 - Previously qualified FSTDs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Previously qualified FSTDs. 60.17 Section 60.17 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION TRAINING DEVICE INITIAL AND CONTINUING QUALIFICATION AND USE § 60.17 Previously...

  5. 14 CFR 60.17 - Previously qualified FSTDs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Previously qualified FSTDs. 60.17 Section 60.17 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION TRAINING DEVICE INITIAL AND CONTINUING QUALIFICATION AND USE § 60.17 Previously...

  6. 14 CFR 60.17 - Previously qualified FSTDs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Previously qualified FSTDs. 60.17 Section 60.17 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION TRAINING DEVICE INITIAL AND CONTINUING QUALIFICATION AND USE § 60.17 Previously...

  7. 14 CFR 60.17 - Previously qualified FSTDs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Previously qualified FSTDs. 60.17 Section 60.17 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION TRAINING DEVICE INITIAL AND CONTINUING QUALIFICATION AND USE § 60.17 Previously...

  8. 14 CFR 60.17 - Previously qualified FSTDs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Previously qualified FSTDs. 60.17 Section 60.17 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION TRAINING DEVICE INITIAL AND CONTINUING QUALIFICATION AND USE § 60.17 Previously...

  9. 49 CFR 173.23 - Previously authorized packaging.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Previously authorized packaging. 173.23 Section... REQUIREMENTS FOR SHIPMENTS AND PACKAGINGS Preparation of Hazardous Materials for Transportation § 173.23 Previously authorized packaging. (a) When the regulations specify a packaging with a specification marking...

  10. Totally extraperitoneal inguinal hernia repair in patients previously having prostatectomy is feasible, safe, and effective.

    PubMed

    Le Page, Philip; Smialkowski, Ania; Morton, Jonathan; Fenton-Lee, Douglas

    2013-12-01

    The laparoscopic approach to repair of inguinal hernia has proven advantages over open repair. Repair of more technically challenging hernias, such as patients previously receiving prostatectomy, has been less studied and may not have these advantages. We aimed to compare safety, feasibility, and clinical outcomes for repairs in patients who previously underwent prostatectomy to control subjects. We undertook a case-control study using a prospectively collected database. From 2004, all patients were routinely offered totally extraperitoneal laparoscopic repair. All patients who had a history of previous prostatectomy were identified and compared to a matched control group. Both operative and follow-up data were analyzed. Of 987 patients undergoing surgery during this time period, 52 prostatectomy patients were identified (44% open, 44% robotic, 3% laparoscopic) and matched to 102 control subjects. Accounting for bilateral repairs, 203 hernia repairs had been performed. Patients were well matched for age and American Society of Anesthesiologists score. Operative time was longer for prostatectomy patients (mean, 70 vs. 52 min, p < 0.0001); however, this reduced over time when comparing the first and second half prostatectomy patients (77 vs. 63 min, p = 0.144). Overall, there were no intraoperative or major postoperative complications and only one conversion (prostatectomy group). No significant differences were found for rates of minor postoperative complications, length of stay, or recurrence (n = 1, control group). No difference was observed for chronic pain, and all patients in each group reported satisfaction with surgery at contemporary follow-up. In experienced hands, totally extraperitoneal inguinal hernia repair for patients previously having undergone prostatectomy is safe and has equivalent outcomes to patients not having undergone prostatectomy, and is an option to open repair. Understandably, slightly longer operative times may be justified, given the

  11. Acute fatal hemorrhage from previously undiagnosed cerebral arteriovenous malformations in children: a single-center experience.

    PubMed

    Riordan, Coleman P; Orbach, Darren B; Smith, Edward R; Scott, R Michael

    2018-06-01

    OBJECTIVE The most significant adverse outcome of intracranial hemorrhage from an arteriovenous malformation (AVM) is death. This study reviews a single-center experience with pediatric AVMs to quantify the incidence and characterize clinical and radiographic factors associated with sudden death from the hemorrhage of previously undiagnosed AVMs in children. METHODS A single-center database review of the period from 2006 to 2017 identified all patients with a first-time intracranial hemorrhage from a previously undiagnosed AVM. Clinical and radiographic data were collected and compared between patients who survived to hospital discharge and those who died at presentation. RESULTS A total of 57 patients (average age 10.8 years, range 0.1-19 years) presented with first-time intracranial hemorrhage from a previously undiagnosed AVM during the study period. Of this group, 7/57 (12%) patients (average age 11.5 years, range 6-16 years) suffered hemorrhages that led directly to their deaths. Compared to the cohort of patients who survived their hemorrhage, patients who died were 4 times more likely to have an AVM in the posterior fossa. No clear pattern of antecedent triggering activity (sports, trauma, etc.) was identified, and 3/7 (43%) experienced cardiac arrest in the prehospital setting. Surviving patients were ultimately treated with resection of the AVM in 42/50 (84%) of cases. CONCLUSIONS Children who present with hemorrhage from a previously undiagnosed intracranial AVM had a 12% chance of sudden death in our single-institution series of pediatric cerebrovascular cases. Clinical triggers of hemorrhage are unpredictable, but subsequent radiographic evidence of a posterior fossa AVM was present in 57% of fatal cases, and all fatal cases were in locations with high risk of potential herniation. These data support a proactive, aggressive approach toward definitive treatment of AVMs in children.

  12. 22 CFR 40.91 - Certain aliens previously removed.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Certain aliens previously removed. 40.91... IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.91 Certain aliens previously removed. (a) 5-year bar. An alien who has been found inadmissible, whether as a result...

  13. 22 CFR 40.91 - Certain aliens previously removed.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Certain aliens previously removed. 40.91... IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.91 Certain aliens previously removed. (a) 5-year bar. An alien who has been found inadmissible, whether as a result...

  14. 22 CFR 40.91 - Certain aliens previously removed.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Certain aliens previously removed. 40.91... IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.91 Certain aliens previously removed. (a) 5-year bar. An alien who has been found inadmissible, whether as a result...

  15. 22 CFR 40.91 - Certain aliens previously removed.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certain aliens previously removed. 40.91... IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.91 Certain aliens previously removed. (a) 5-year bar. An alien who has been found inadmissible, whether as a result...

  16. 22 CFR 40.91 - Certain aliens previously removed.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Certain aliens previously removed. 40.91... IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.91 Certain aliens previously removed. (a) 5-year bar. An alien who has been found inadmissible, whether as a result...

  17. 18 CFR 154.302 - Previously submitted material.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Previously submitted material. 154.302 Section 154.302 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.302 Previously submitted material. (a) If all, or any portion, of the...

  18. 18 CFR 154.302 - Previously submitted material.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Previously submitted material. 154.302 Section 154.302 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.302 Previously submitted material. (a) If all, or any portion, of the...

  19. 18 CFR 154.302 - Previously submitted material.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Previously submitted material. 154.302 Section 154.302 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.302 Previously submitted material. (a) If all, or any portion, of the...

  20. 18 CFR 154.302 - Previously submitted material.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Previously submitted material. 154.302 Section 154.302 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.302 Previously submitted material. (a) If all, or any portion, of the...

  1. Medical evacuation for unrecognized abdominal wall pain: a case series.

    PubMed

    Msonda, Hapu T; Laczek, Jeffrey T

    2015-05-01

    Chronic abdominal pain is a frequently encountered complaint in the primary care setting. The abdominal wall is the etiology of this pain in 10 to 30% of all cases of chronic abdominal pain. Abdominal cutaneous nerve entrapment at the lateral border of the rectus abdominis muscle has been attributed as a cause of this pain. In the military health care system, patients with unexplained abdominal pain are often transferred to military treatment facilities via the Military Medical Evacuation (MEDEVAC) system. We present two cases of patients who transferred via MEDEVAC to our facility for evaluation and treatment of chronic abdominal pain. Both patients had previously undergone extensive laboratory evaluation, imaging, and invasive procedures, such as esophagogastroduodenoscopy before transfer. Upon arrival, history and physical examinations suggested an abdominal wall source to their pain, and both patients experienced alleviation of their abdominal wall pain with lidocaine and corticosteroid injection. This case series highlights the need for military physicians to be aware of abdominal wall pain. Early diagnosis of abdominal cutaneous nerve entrapment syndrome by eliciting Carnett's sign will limit symptom chronicity, avoid unnecessary testing, and even prevent medical evacuation. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

  2. Age, training, and previous experience predict race performance in long-distance inline skaters, not anthropometry.

    PubMed

    Knechtle, Beat; Knechtle, Patrizia; Rüst, Christoph Alexander; Rosemann, Thomas; Lepers, Romuald

    2012-02-01

    The association of characteristics of anthropometry, training, and previous experience with race time in 84 recreational, long-distance, inline skaters at the longest inline marathon in Europe (111 km), the Inline One-eleven in Switzerland, was investigated to identify predictor variables for performance. Age, duration per training unit, and personal best time were the only three variables related to race time in a multiple regression, while none of the 16 anthropometric variables were related. Anthropometric characteristics seem to be of no importance for a fast race time in a long-distance inline skating race in contrast to training volume and previous experience, when controlled with covariates. Improving performance in a long-distance inline skating race might be related to a high training volume and previous race experience. Also, doing such a race requires a parallel psychological effort, mental stamina, focus, and persistence. This may be reflected in the preparation and training for the event. Future studies should investigate what motivates these athletes to train and compete.

  3. Germline mutation prevalence in individuals with pancreatic cancer and a history of previous malignancy.

    PubMed

    Dudley, Beth; Karloski, Eve; Monzon, Federico A; Singhi, Aatur D; Lincoln, Stephen E; Bahary, Nathan; Brand, Randall E

    2018-04-15

    Approximately 10% of pancreatic adenocarcinoma (PC) cases are attributed to hereditary causes. Individuals with PC and a personal history of another cancer associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) may be more likely to carry germline mutations. Participants with PC and a history of cancer were selected from a pancreatic disease registry. Of 1296 individuals with PC, 149 had a relevant history of cancer. If banked DNA was available, a multigene panel was performed for individuals who had not 1) previously had a mutation identified through clinical testing or 2) undergone clinical multigene panel testing with no mutations detected. Twenty-two of 124 individuals with PC and another HBOC- or LS-related cancer who underwent genetic testing had a mutation identified in a PC susceptibility gene (18%). If prostate cancer is excluded, the mutation prevalence increased to 23% (21/93). Mutation carriers were more likely to have more than 1 previous cancer diagnosis (P = .001), to have had clinical genetic testing (P = .001), and to meet National Comprehensive Cancer Network (NCCN) genetic testing criteria (P < .001). Approximately 23% of mutation carriers did not meet NCCN HBOC or LS testing guidelines based on their personal cancer history and reported cancer history in first-degree relatives. At least 18% of individuals with PC and a personal history of other HBOC- or LS-related cancers carry mutations in a PC susceptibility gene based on our data, suggesting that criteria for genetic testing in individuals with PC should include consideration of previous cancer history. Cancer 2018;124:1691-700. © 2018 American Cancer Society. © 2018 American Cancer Society.

  4. Vaginal delivery after previous caesarean section: is X-ray pelvimetry necessary?

    PubMed

    Thubisi, M; Ebrahim, A; Moodley, J; Shweni, P M

    1993-05-01

    To determine whether antepartum X-ray pelvimetry (XRP) reliably identified women suitable for a trial labour or repeat elective caesarean section after one previous section. A prospective controlled trial in which women were randomly allocated to either an antepartum XRP group who had XRP at 36 weeks gestation to determine mode of delivery, or a control group who had a trial labour without antepartum XRP. Following delivery, all controls had postpartum XRP. Department of Obstetrics and Gynaecology, King Edward VIII Hospital, Durban, South Africa. Three hundred-six women with a history of one previous caesarean section. Mode of delivery, birthweight and maternal and perinatal mortality and morbidity in the two groups. In the antepartum XRP group, 23 of 144 (16%) of women delivered vaginally compared with 60 of 144 (42%) controls (P < 0.0001). Of the 84 women with adequate antepartum XRP only 23 (27.7%) delivered vaginally. In the control group, 33 of 60 (55%) women who had vaginal deliveries had inadequate postpartum XRP and would have had a caesarean section if this information was known in the antepartum period; 62 of 84 (74%) caesarean sections in the control group had adequate postpartum XRP. Birthweight of the infants was similar in the two groups. There were no maternal or perinatal deaths. Maternal morbidity was similar in the two groups. Neonatal morbidity was minimal. Antepartum XRP is not necessary prior to a trial labour in women with one previous caesarean section. It increases the caesarean section rate and is a poor predictor of the outcome of labour.

  5. Neurodevelopment and Chronic Illness: Mechanisms of Disease and Treatment

    ERIC Educational Resources Information Center

    Armstrong, F. Daniel

    2006-01-01

    Successful treatment of many childhood diseases once considered terminal has resulted in the emergence of long-term effects of the disease or consequences of treatment that were previously unrecognized. Many of these long-term effects involve the central nervous system (CNS) and are developmental in the way that they emerge over time. Because we…

  6. Shifting from Implicit to Explicit Knowledge: Different Roles of Early- and Late-Night Sleep

    ERIC Educational Resources Information Center

    Yordanova, Juliana; Kolev, Vasil; Verleger, Rolf; Bataghva, Zhamak; Born, Jan; Wagner, Ullrich

    2008-01-01

    Sleep has been shown to promote the generation of explicit knowledge as indicated by the gain of insight into previously unrecognized task regularities. Here, we explored whether this generation of explicit knowledge depends on pre-sleep implicit knowledge, and specified the differential roles of slow-wave sleep (SWS) vs. rapid eye movement (REM)…

  7. Identifying cooperative transcriptional regulations using protein–protein interactions

    PubMed Central

    Nagamine, Nobuyoshi; Kawada, Yuji; Sakakibara, Yasubumi

    2005-01-01

    Cooperative transcriptional activations among multiple transcription factors (TFs) are important to understand the mechanisms of complex transcriptional regulations in eukaryotes. Previous studies have attempted to find cooperative TFs based on gene expression data with gene expression profiles as a measure of similarity of gene regulations. In this paper, we use protein–protein interaction data to infer synergistic binding of cooperative TFs. Our fundamental idea is based on the assumption that genes contributing to a similar biological process are regulated under the same control mechanism. First, the protein–protein interaction networks are used to calculate the similarity of biological processes among genes. Second, we integrate this similarity and the chromatin immuno-precipitation data to identify cooperative TFs. Our computational experiments in yeast show that predictions made by our method have successfully identified eight pairs of cooperative TFs that have literature evidences but could not be identified by the previous method. Further, 12 new possible pairs have been inferred and we have examined the biological relevances for them. However, since a typical problem using protein–protein interaction data is that many false-positive data are contained, we propose a method combining various biological data to increase the prediction accuracy. PMID:16126847

  8. A nonmusical paradigm for identifying absolute pitch possessors

    NASA Astrophysics Data System (ADS)

    Ross, David A.; Olson, Ingrid R.; Marks, Lawrence E.; Gore, John C.

    2004-09-01

    The ability to identify and reproduce sounds of specific frequencies is remarkable and uncommon. The etiology and defining characteristics of this skill, absolute pitch (AP), have been very controversial. One theory suggests that AP requires a specific type of early musical training and that the ability to encode and remember tones depends on these learned musical associations. An alternate theory argues that AP may be strongly dependent on hereditary factors and relatively independent of musical experience. To date, it has been difficult to test these hypotheses because all previous paradigms for identifying AP have required subjects to employ knowledge of musical nomenclature. As such, these tests are insensitive to the possibility of discovering AP in either nonmusicians or musicians of non-Western training. Based on previous literature in pitch memory, a paradigm is presented that is intended to distinguish between AP possessors and nonpossessors independent of the subjects' musical experience. The efficacy of this method is then tested with 20 classically defined AP possessors and 22 nonpossessors. Data from these groups strongly support the validity of the paradigm. The use of a nonmusical paradigm to identify AP may facilitate research into many aspects of this phenomenon.

  9. A nonmusical paradigm for identifying absolute pitch possessors.

    PubMed

    Ross, David A; Olson, Ingrid R; Marks, Lawrence E; Gore, John C

    2004-09-01

    The ability to identify and reproduce sounds of specific frequencies is remarkable and uncommon. The etiology and defining characteristics of this skill, absolute pitch (AP), have been very controversial. One theory suggests that AP requires a specific type of early musical training and that the ability to encode and remember tones depends on these learned musical associations. An alternate theory argues that AP may be strongly dependent on hereditary factors and relatively independent of musical experience. To date, it has been difficult to test these hypotheses because all previous paradigms for identifying AP have required subjects to employ knowledge of musical nomenclature. As such, these tests are insensitive to the possibility of discovering AP in either nonmusicians or musicians of non-Western training. Based on previous literature in pitch memory, a paradigm is presented that is intended to distinguish between AP possessors and nonpossessors independent of the subjects' musical experience. The efficacy of this method is then tested with 20 classically defined AP possessors and 22 nonpossessors. Data from these groups strongly support the validity of the paradigm. The use of a nonmusical paradigm to identify AP may facilitate research into many aspects of this phenomenon.

  10. Ivy and neurogliaform interneurons are a major target of μ opioid receptor modulation

    PubMed Central

    Krook-Magnuson, Esther; Luu, Lillian; Lee, Sang-Hun; Varga, Csaba; Soltesz, Ivan

    2011-01-01

    Mu opioid receptors (μORs) are selectively expressed on interneurons in area CA1 of the hippocampus. Fast-spiking, parvalbumin expressing, basket cells express μORs, but circumstantial evidence suggests that another major, unidentified, GABAergic cell class must also be modulated by μORs. Here we report that the abundant, dendritically targeting, neurogliaform family of cells (Ivy and neurogliaform cells) is a previously unrecognized target of direct modulation by μORs. Ivy and neurogliaform cells are not only numerous, but also have unique properties, including promiscuous gap junctions formed with various interneuronal subtypes, volume transmission, and the ability to produce a postsynaptic GABAB response after a single presynaptic spike. Using a mouse line expressing green fluorescent protein under the neuropeptide Y promoter, we find that across all layers of CA1, activation of μORs hyperpolarizes Ivy and neurogliaform cells. Further, paired recordings between synaptically coupled Ivy and pyramidal cells show that Ivy cell terminals are dramatically inhibited by μOR-activation. Effects in Ivy and neurogliaform cells are seen at similar concentrations of agonist as those producing inhibition in fast-spiking PV basket cells. We also report that Ivy cells display the recently described phenomenon of persistent firing, a state of continued firing in the absence of continued input, and that induction of persistent firing is inhibited by μOR-activation. Together these findings identify a major, previously unrecognized, target of μOR-modulation. Given the prominence of this cell type in and beyond CA1, as well as its unique role in microcircuitry, opioid modulation of neurogliaform cells has wide implications. PMID:22016519

  11. Ivy and neurogliaform interneurons are a major target of μ-opioid receptor modulation.

    PubMed

    Krook-Magnuson, Esther; Luu, Lillian; Lee, Sang-Hun; Varga, Csaba; Soltesz, Ivan

    2011-10-19

    μ-Opioid receptors (μORs) are selectively expressed on interneurons in area CA1 of the hippocampus. Fast-spiking, parvalbumin-expressing, basket cells express μORs, but circumstantial evidence suggests that another major, unidentified, GABAergic cell class must also be modulated by μORs. Here we report that the abundant, dendritically targeting, neurogliaform family of cells (Ivy and neurogliaform cells) is a previously unrecognized target of direct modulation by μORs. Ivy and neurogliaform cells are not only numerous but also have unique properties, including promiscuous gap junctions formed with various interneuronal subtypes, volume transmission, and the ability to produce a postsynaptic GABA(B) response after a single presynaptic spike. Using a mouse line expressing green fluorescent protein under the neuropeptide Y promoter, we find that, across all layers of CA1, activation of μORs hyperpolarizes Ivy and neurogliaform cells. Furthermore, paired recordings between synaptically coupled Ivy and pyramidal cells show that Ivy cell terminals are dramatically inhibited by μOR activation. Effects in Ivy and neurogliaform cells are seen at similar concentrations of agonist as those producing inhibition in fast-spiking parvalbumin basket cells. We also report that Ivy cells display the recently described phenomenon of persistent firing, a state of continued firing in the absence of continued input, and that induction of persistent firing is inhibited by μOR activation. Together, these findings identify a major, previously unrecognized, target of μOR modulation. Given the prominence of this cell type in and beyond CA1, as well as its unique role in microcircuitry, opioid modulation of neurogliaform cells has wide implications.

  12. Src homology 2 domain-containing phosphatase 2 (Shp2) is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex and is inhibited by protein kinase A (PKA) under pathological hypertrophic conditions in the heart.

    PubMed

    Burmeister, Brian T; Taglieri, Domenico M; Wang, Li; Carnegie, Graeme K

    2012-11-23

    AKAP-Lbc is a scaffold protein that coordinates cardiac hypertrophic signaling. AKAP-Lbc interacts with Shp2, facilitating its regulation by PKA. AKAP-Lbc integrates PKA and Shp2 signaling in the heart. Under pathological hypertrophic conditions Shp2 is phosphorylated by PKA, and phosphatase activity is inhibited. Inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote pathological cardiac hypertrophy. Pathological cardiac hypertrophy (an increase in cardiac mass resulting from stress-induced cardiac myocyte growth) is a major factor underlying heart failure. Our results identify a novel mechanism of Shp2 inhibition that may promote cardiac hypertrophy. We demonstrate that the tyrosine phosphatase, Shp2, is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex. AKAP-Lbc facilitates PKA phosphorylation of Shp2, which inhibits its protein-tyrosine phosphatase activity. Given the important cardiac roles of both AKAP-Lbc and Shp2, we investigated the AKAP-Lbc-Shp2 interaction in the heart. AKAP-Lbc-tethered PKA is implicated in cardiac hypertrophic signaling; however, mechanism of PKA action is unknown. Mutations resulting in loss of Shp2 catalytic activity are also associated with cardiac hypertrophy and congenital heart defects. Our data indicate that AKAP-Lbc integrates PKA and Shp2 signaling in the heart and that AKAP-Lbc-associated Shp2 activity is reduced in hypertrophic hearts in response to chronic β-adrenergic stimulation and PKA activation. Thus, while induction of cardiac hypertrophy is a multifaceted process, inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote compensatory cardiac hypertrophy.

  13. Viral Surveillance in Serum Samples From Patients With Acute Liver Failure By Metagenomic Next-Generation Sequencing.

    PubMed

    Somasekar, Sneha; Lee, Deanna; Rule, Jody; Naccache, Samia N; Stone, Mars; Busch, Michael P; Sanders, Corron; Lee, William M; Chiu, Charles Y

    2017-10-16

    Twelve percent of all acute liver failure (ALF) cases are of unknown origin, often termed indeterminate. A previously unrecognized hepatotropic virus has been suspected as a potential etiologic agent. We compared the performance of metagenomic next-generation sequencing (mNGS) with confirmatory nucleic acid testing (NAT) to routine clinical diagnostic testing in detection of known or novel viruses associated with ALF. Serum samples from 204 adult ALF patients collected from 1998 to 2010 as part of a nationwide registry were analyzed. One hundred eighty-seven patients (92%) were classified as indeterminate, while the remaining 17 patients (8%) served as controls, with infections by either hepatitis A virus or hepatitis B virus (HBV), or a noninfectious cause for their ALF. Eight cases of infection from previously unrecognized viral pathogens were detected by mNGS (4 cases of herpes simplex virus type 1, including 1 case of coinfection with HBV, and 1 case each of HBV, parvovirus B19, cytomegalovirus, and human herpesvirus 7). Several missed dual or triple infections were also identified, and assembled viral genomes provided additional information on genotyping and drug resistance mutations. Importantly, no sequences corresponding to novel viruses were detected. These results suggest that ALF patients should be screened for the presence of uncommon viruses and coinfections, and that most cases of indeterminate ALF in the United States do not appear to be caused by novel viral pathogens. In the future, mNGS testing may be useful for comprehensive diagnosis of viruses associated with ALF, or to exclude infectious etiologies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Association between previous spontaneous abortion and pre-eclampsia during a subsequent pregnancy.

    PubMed

    Sepidarkish, Mahdi; Almasi-Hashiani, Amir; Maroufizadeh, Saman; Vesali, Samira; Pirjani, Reihaneh; Samani, Reza O

    2017-01-01

    To determine the impact of a history of spontaneous abortion on pre-eclampsia during a subsequent pregnancy. A cross-sectional study enrolled pregnant women admitted to obstetrics and gynecology wards at 103 hospitals in Tehran, Iran for delivery between July 6 and July 21, 2015. Consenting participants were interviewed by midwives; data were collected using a five-part questionnaire and patients' medical records were retrieved. Patient data were analyzed by multiple logistic regression to identify variables associated with increased odds of pre-eclampsia. In total, 5170 patients were interviewed and 252 had experienced pre-eclampsia. The number of previous spontaneous abortions was found to be associated with pre-eclampsia, and a higher number of previous spontaneous abortions was associated with increased odds of patients having experienced pre-eclampsia (adjusted odds ratio 1.28, 95% confidence interval 1.03-1.59; P=0.025). A history of spontaneous abortion was associated with increased odds of pre-eclampsia during a subsequent pregnancy. © 2016 International Federation of Gynecology and Obstetrics.

  15. Comprehensive Genomic Profiling Identifies Frequent Drug-Sensitive EGFR Exon 19 Deletions in NSCLC not Identified by Prior Molecular Testing.

    PubMed

    Schrock, Alexa B; Frampton, Garrett M; Herndon, Dana; Greenbowe, Joel R; Wang, Kai; Lipson, Doron; Yelensky, Roman; Chalmers, Zachary R; Chmielecki, Juliann; Elvin, Julia A; Wollner, Mira; Dvir, Addie; -Gutman, Lior Soussan; Bordoni, Rodolfo; Peled, Nir; Braiteh, Fadi; Raez, Luis; Erlich, Rachel; Ou, Sai-Hong Ignatius; Mohamed, Mohamed; Ross, Jeffrey S; Stephens, Philip J; Ali, Siraj M; Miller, Vincent A

    2016-07-01

    Reliable detection of drug-sensitive activating EGFR mutations is critical in the care of advanced non-small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation. A large pool of NSCLC cases was assayed with well-validated, hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. From these, 400 cases harboring EGFR exon 19 deletions (Δex19) were identified, and available clinical history was reviewed. Pathology reports were available for 250 consecutive cases with classical EGFR Δex19 (amino acids 743-754) and were reviewed to assess previous non-hybrid capture-based EGFR testing. Twelve of 71 (17%) cases with EGFR testing results available were negative by previous testing, including 8 of 46 (17%) cases for which the same biopsy was analyzed. Independently, five of six (83%) cases harboring C-helical EGFR Δex19 were previously negative. In a subset of these patients with available clinical outcome information, robust benefit from treatment with EGFR inhibitors was observed. CGP identifies drug-sensitive EGFR Δex19 in NSCLC cases that have undergone prior EGFR testing and returned negative results. Given the proven benefit in progression-free survival conferred by EGFR tyrosine kinase inhibitors in patients with these alterations, CGP should be considered in the initial presentation of advanced NSCLC and when previous testing for EGFR mutations or other driver alterations is negative. Clin Cancer Res; 22(13); 3281-5. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. Random plasma glucose in serendipitous screening for glucose intolerance: screening for impaired glucose tolerance study 2.

    PubMed

    Ziemer, David C; Kolm, Paul; Foster, Jovonne K; Weintraub, William S; Vaccarino, Viola; Rhee, Mary K; Varughese, Rincy M; Tsui, Circe W; Koch, David D; Twombly, Jennifer G; Narayan, K M Venkat; Phillips, Lawrence S

    2008-05-01

    With positive results from diabetes prevention studies, there is interest in convenient ways to incorporate screening for glucose intolerance into routine care and to limit the need for fasting diagnostic tests. The aim of this study is to determine whether random plasma glucose (RPG) could be used to screen for glucose intolerance. This is a cross-sectional study. The participants of this study include a voluntary sample of 990 adults not known to have diabetes. RPG was measured, and each subject had a 75-g oral glucose tolerance test several weeks later. Glucose intolerance targets included diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose(110) (IFG(110); fasting glucose, 110-125 mg/dl, and 2 h glucose < 140 mg/dl). Screening performance was measured by area under receiver operating characteristic curves (AROC). Mean age was 48 years, and body mass index (BMI) was 30.4 kg/m(2); 66% were women, and 52% were black; 5.1% had previously unrecognized diabetes, and 24.0% had any "high-risk" glucose intolerance (diabetes or IGT or IFG(110)). The AROC was 0.80 (95% CI 0.74-0.86) for RPG to identify diabetes and 0.72 (0.68-0.75) to identify any glucose intolerance, both highly significant (p < 0.001). Screening performance was generally consistent at different times of the day, regardless of meal status, and across a range of risk factors such as age, BMI, high density lipoprotein cholesterol, triglycerides, and blood pressure. RPG values should be considered by health care providers to be an opportunistic initial screening test and used to prompt further evaluation of patients at risk of glucose intolerance. Such "serendipitous screening" could help to identify unrecognized diabetes and prediabetes.

  17. Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus.

    PubMed

    Moon, Joon Ho; Kwak, Soo Heon; Jang, Hak C

    2017-01-01

    Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is characterized by underlying maternal defects in the β-cell response to insulin during pregnancy. Women with a previous history of GDM have a greater than 7-fold higher risk of developing postpartum diabetes compared with women without GDM. Various risk factors for postpartum diabetes have been identified, including maternal age, glucose levels in pregnancy, family history of diabetes, pre-pregnancy and postpartum body mass index, dietary patterns, physical activity, and breastfeeding. Genetic studies revealed that GDM shares common genetic variants with type 2 diabetes. A number of lifestyle interventional trials that aimed to ameliorate modifiable risk factors, including diet, exercise, and breastfeeding, succeeded in reducing the incidence of postpartum diabetes, weight retention, and other obesity-related morbidities. The present review summarizes the findings of previous studies on the incidence and risk factors of postpartum diabetes and discusses recent lifestyle interventional trials that attempted to prevent postpartum diabetes.

  18. Identifying web usage behavior of bank customers

    NASA Astrophysics Data System (ADS)

    Araya, Sandro; Silva, Mariano; Weber, Richard

    2002-03-01

    The bank Banco Credito e Inversiones (BCI) started its virtual bank in 1996 and its registered customers perform currently more than 10,000 Internet transactions daily, which typically cause les than 10% of traditional transaction costs. Since most of the customers are still not registered for online banking, one of the goals of the virtual bank is to increase then umber of registered customers. Objective of the presented work was to identify customers who are likely to perform online banking but still do not use this medium for their transactions. This objective has been reached by determining profiles of registered customers who perform many transactions online. Based on these profiles the bank's Data Warehouse is explored for twins of these heavy users that are still not registered for online banking. We applied clustering in order to group the registered customers into five classes. One of these classes contained almost 30% of all registered customers and could clearly be identified as class of heavy users. Next a neural network assigned online customers to the previously found five classes. Applying the network trained on online customers to all the bank customers identified twins of heavy users that, however had not performed online transactions so far. A mailing to these candidates informing about the advantages of online banking doubled the number of registrations compared to previous campaigns.

  19. Individual heterogeneity and identifiability in capture-recapture models

    USGS Publications Warehouse

    Link, W.A.

    2004-01-01

    Individual heterogeneity in detection probabilities is a far more serious problem for capture-recapture modeling than has previously been recognized. In this note, I illustrate that population size is not an identifiable parameter under the general closed population mark-recapture model Mh. The problem of identifiability is obvious if the population includes individuals with pi = 0, but persists even when it is assumed that individual detection probabilities are bounded away from zero. Identifiability may be attained within parametric families of distributions for pi, but not among parametric families of distributions. Consequently, in the presence of individual heterogeneity in detection probability, capture-recapture analysis is strongly model dependent.

  20. Erythema after laser skin resurfacing.

    PubMed

    Ruiz-Esparza, J; Barba Gomez, J M; Gomez de la Torre, O L; David, L

    1998-01-01

    Erythema after laser skin resurfacing is seen by many as a necessary evil in order to get good results from the procedure. A critical review of widely accepted concepts may lead to diminishing the length of postoperative erythema in patients undergoing laser resurfacing. The authors report on two previously unrecognized factors in the causation of this problem.

  1. Portable diagnostic devices for identifying obstructive sleep apnea among commercial motor vehicle drivers: considerations and unanswered questions.

    PubMed

    Zhang, Chunbai; Berger, Mark; Malhotra, Atul; Kales, Stefanos N

    2012-11-01

    Obstructive sleep apnea (OSA), a syndrome defined by breathing abnormalities during sleep, can lead to fatigue and excessive daytime sleepiness (EDS) with an increased risk of motor vehicle crashes. Identifying commercial motor vehicle operators with unrecognized OSA is a major public health priority. Portable monitors (PMs) are being actively marketed to trucking firms as potentially lower-cost and more accessible alternatives to the reference standard of in-laboratory polysomnography (PSG) in the diagnosis of OSA among commercial motor vehicle operators. Several factors regarding PMs remain uncertain in this unique patient population: their sensitivity and specificity; the cost-benefit ratio of the PMs versus PSG; potential barriers from human factors; and evolving technologic advancement. Human factors that alter test accuracy are a major concern among commercial drivers motivated to gain/maintain employment. Current available data using PMs as a diagnostic tool among CMV operators indicate relatively high data loss and high loss to follow-up. Loss to follow-up has also been an issue using PSG in commercial motor vehicle operators. Furthermore, PM testing and PM results interpretation protocols may have no sleep specialist oversight, and sometimes minimal physician oversight and involvement. Additional studies comparing unattended and unmonitored PMs directly against full in-laboratory PSG are needed to provide evidence for their efficacy among commercial motor vehicle operators.

  2. Natural Variation in the Promoter of GSE5 Contributes to Grain Size Diversity in Rice.

    PubMed

    Duan, Penggen; Xu, Jinsong; Zeng, Dali; Zhang, Baolan; Geng, Mufan; Zhang, Guozheng; Huang, Ke; Huang, Luojiang; Xu, Ran; Ge, Song; Qian, Qian; Li, Yunhai

    2017-05-01

    The utilization of natural genetic variation greatly contributes to improvement of important agronomic traits in crops. Understanding the genetic basis for natural variation of grain size can help breeders develop high-yield rice varieties. In this study, we identify a previously unrecognized gene, named GSE5, in the qSW5/GW5 locus controlling rice grain size by combining the genome-wide association study with functional analyses. GSE5 encodes a plasma membrane-associated protein with IQ domains, which interacts with the rice calmodulin protein, OsCaM1-1. We found that loss of GSE5 function caused wide and heavy grains, while overexpression of GSE5 resulted in narrow grains. We showed that GSE5 regulates grain size predominantly by influencing cell proliferation in spikelet hulls. Three major haplotypes of GSE5 (GSE5, GSE5 DEL1+IN1 , and GSE5 DEL2 ) in cultivated rice were identified based on the deletion/insertion type in its promoter region. We demonstrated that a 950-bp deletion (DEL1) in indica varieties carrying the GSE5 DEL1+IN1 haplotype and a 1212-bp deletion (DEL2) in japonica varieties carrying the GSE5 DEL2 haplotype associated with decreased expression of GSE5, resulting in wide grains. Further analyses indicate that wild rice accessions contain all three haplotypes of GSE5, suggesting that the GSE5 haplotypes present in cultivated rice are likely to have originated from different wild rice accessions during rice domestication. Taken together, our results indicate that the previously unrecognized GSE5 gene in the qSW5/GW5 locus, which is widely utilized by rice breeders, controls grain size, and reveal that natural variation in the promoter region of GSE5 contributes to grain size diversity in rice. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  3. Intelligence in DSM-IV combined type attention-deficit/hyperactivity disorder is not predicted by either dopamine receptor/transporter genes or other previously identified risk alleles for attention-deficit/hyperactivity disorder.

    PubMed

    Sonuga-Barke, Edmund J S; Brookes, Keeley-Joanne; Buitelaar, Jan; Anney, Richard; Bitsakou, Paraskevi; Baeyens, Dieter; Buschgens, Cathelijne; Chen, Wai; Christiansen, Hanna; Eisenberg, Jacques; Kuntsi, Jonna; Manor, Iris; Meliá, Amanda; Mulligan, Aisling; Rommelse, Nanda; Müller, Ueli C; Uebel, Henrik; Banaschewski, Tobias; Ebstein, Richard; Franke, Barbara; Gill, Michael; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Steinhausen, Hans Christoph; Thompson, Margaret; Taylor, Eric; Asherson, Philip; Faraone, Stephen V

    2008-04-05

    A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify individual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] findings in a clinical sample and to extend the analysis to a large range of alternative SNP markers of putative ADHD risk alleles identified in a recent study [Brookes et al. (2006); Mol Genet 11:934-953]. Participants were 1081 children and adolescents with a research-confirmed combined type ADHD diagnosis and 1300 unaffected siblings who took part in the International Multi-centre ADHD Genetics (IMAGE) project. They were recruited from multiple settings from across Europe: Belgium, Britain, Germany, Ireland, Israel, Netherlands, Spain and Switzerland. The results were that ADHD was associated with reduced IQ. However, there was no association between the two dopamine-related risk polymorphisms and IQ in either the probands or their siblings. Furthermore, other selected genetic markers previously demonstrated to be associated with ADHD in this sample were not associated with IQ. This large scale study with a clinically ascertained and regorously diagnosed sample failed to replicate the association between genetic polymorphisms in the dopamine system and IQ in ADHD. We also observed no association of other SNPs with IQ in ADHD. Copyright 2007 Wiley-Liss, Inc.

  4. Characterization and complete genome sequence of a previously uncharacterized panicovirus from Bermuda grass detected by high throughput sequencing

    USDA-ARS?s Scientific Manuscript database

    Bermuda grass samples were examined by transmission electron microscopy and 28-30 nm spherical virus particles were observed. Total RNA from these plants was subjected to high throughput sequencing (HTS). The nearly full genome sequence of a previously uncharacterized Panicovirus was identified from...

  5. Predictors of self-reported negative mood following a depressive mood induction procedure across previously depressed, currently anxious, and control individuals.

    PubMed

    Scherrer, Martin C; Dobson, Keith S; Quigley, Leanne

    2014-09-01

    This study identified and examined a set of potential predictors of self-reported negative mood following a depressive mood induction procedure (MIP) in a sample of previously depressed, clinically anxious, and control participants. The examined predictor variables were selected on the basis of previous research and theories of depression, and included symptoms of depression and anxiety, negative and positive affect, negative and positive automatic thoughts, dysfunctional beliefs, rumination, self-concept, and occurrence and perceived unpleasantness of recent negative events. The sample consisted of 33 previously depressed, 22 currently anxious, and 26 non-clinical control participants, recruited from community sources. Participant group status was confirmed through structured diagnostic interviews. Participants completed the Velten negative self-statement MIP as well as self-report questionnaires of affective, cognitive, and psychosocial variables selected as potential predictors of mood change. Symptoms of anxiety were associated with increased self-reported negative mood shift following the MIP in previously depressed participants, but not clinically anxious or control participants. Increased occurrence of recent negative events was a marginally significant predictor of negative mood shift for the previously depressed participants only. None of the other examined variables was significant predictors of MIP response for any of the participant groups. These results identify factors that may increase susceptibility to negative mood states in previously depressed individuals, with implications for theory and prevention of relapse to depression. The findings also identify a number of affective, cognitive, and psychosocial variables that do not appear to influence mood change following a depressive MIP in previously depressed, currently anxious, and control individuals. Limitations of the study and directions for future research are discussed. Current anxiety

  6. The early postpartum experience of previously infertile mothers.

    PubMed

    Ladores, Sigrid; Aroian, Karen

    2015-01-01

    To explore the lived experience of becoming a new mother from the unique perspectives of previously infertile women. A descriptive phenomenological design was used to extract the fundamental structure of the postpartum experience of previously infertile mothers. Central Florida. Twelve first-time, previously infertile mothers age 27 to 43 years. Face-to-face interviews were conducted twice with each participant. Recorded interviews were transcribed verbatim and analyzed using Colaizzi's approach. Two main themes emerged that described the early postpartum experience of first-time, previously infertile mothers: (a) lingering identity as infertile and (b) gratitude for the gift of motherhood. Participants reported that their lingering identities as infertile and immense gratitude for the gift of motherhood propelled them to establish unrealistic expectations to be perfect mothers. When they were unable to live up this expectation, they censored their feelings of inadequacy, guilt, and shame. Findings from this study may help to sensitize health care providers to the difficulties faced by previously infertile women during their transition to motherhood. © 2015 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

  7. No Previous Public Services Required

    ERIC Educational Resources Information Center

    Taylor, Kelley R.

    2009-01-01

    In 2007, the Supreme Court heard a case that involved the question of whether a school district could be required to reimburse parents who unilaterally placed their child in private school when the child had not previously received special education and related services in a public institution ("Board of Education v. Tom F."). The…

  8. Immortal time bias: a frequently unrecognized threat to validity in the evaluation of postoperative radiotherapy.

    PubMed

    Park, Henry S; Gross, Cary P; Makarov, Danil V; Yu, James B

    2012-08-01

    To evaluate the influence of immortal time bias on observational cohort studies of postoperative radiotherapy (PORT) and the effectiveness of sequential landmark analysis to account for this bias. First, we reviewed previous studies of the Surveillance, Epidemiology, and End Results (SEER) database to determine how frequently this bias was considered. Second, we used SEER to select three tumor types (glioblastoma multiforme, Stage IA-IVM0 gastric adenocarcinoma, and Stage II-III rectal carcinoma) for which prospective trials demonstrated an improvement in survival associated with PORT. For each tumor type, we calculated conditional survivals and adjusted hazard ratios of PORT vs. postoperative observation cohorts while restricting the sample at sequential monthly landmarks. Sixty-two percent of previous SEER publications evaluating PORT failed to use a landmark analysis. As expected, delivery of PORT for all three tumor types was associated with improved survival, with the largest associated benefit favoring PORT when all patients were included regardless of survival. Preselecting a cohort with a longer minimum survival sequentially diminished the apparent benefit of PORT. Although the majority of previous SEER articles do not correct for it, immortal time bias leads to altered estimates of PORT effectiveness, which are very sensitive to landmark selection. We suggest the routine use of sequential landmark analysis to account for this bias. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Immortal Time Bias: A Frequently Unrecognized Threat to Validity in the Evaluation of Postoperative Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Henry S.; Gross, Cary P.; Makarov, Danil V.

    2012-08-01

    Purpose: To evaluate the influence of immortal time bias on observational cohort studies of postoperative radiotherapy (PORT) and the effectiveness of sequential landmark analysis to account for this bias. Methods and Materials: First, we reviewed previous studies of the Surveillance, Epidemiology, and End Results (SEER) database to determine how frequently this bias was considered. Second, we used SEER to select three tumor types (glioblastoma multiforme, Stage IA-IVM0 gastric adenocarcinoma, and Stage II-III rectal carcinoma) for which prospective trials demonstrated an improvement in survival associated with PORT. For each tumor type, we calculated conditional survivals and adjusted hazard ratios of PORTmore » vs. postoperative observation cohorts while restricting the sample at sequential monthly landmarks. Results: Sixty-two percent of previous SEER publications evaluating PORT failed to use a landmark analysis. As expected, delivery of PORT for all three tumor types was associated with improved survival, with the largest associated benefit favoring PORT when all patients were included regardless of survival. Preselecting a cohort with a longer minimum survival sequentially diminished the apparent benefit of PORT. Conclusions: Although the majority of previous SEER articles do not correct for it, immortal time bias leads to altered estimates of PORT effectiveness, which are very sensitive to landmark selection. We suggest the routine use of sequential landmark analysis to account for this bias.« less

  10. Comparative promoter analysis allows de novo identification of specialized cell junction-associated proteins.

    PubMed

    Cohen, Clemens D; Klingenhoff, Andreas; Boucherot, Anissa; Nitsche, Almut; Henger, Anna; Brunner, Bodo; Schmid, Holger; Merkle, Monika; Saleem, Moin A; Koller, Klaus-Peter; Werner, Thomas; Gröne, Hermann-Josef; Nelson, Peter J; Kretzler, Matthias

    2006-04-11

    Shared transcription factor binding sites that are conserved in distance and orientation help control the expression of gene products that act together in the same biological context. New bioinformatics approaches allow the rapid characterization of shared promoter structures and can be used to find novel interacting molecules. Here, these principles are demonstrated by using molecules linked to the unique functional unit of the glomerular slit diaphragm. An evolutionarily conserved promoter model was generated by comparative genomics in the proximal promoter regions of the slit diaphragm-associated molecule nephrin. Phylogenetic promoter fingerprints of known elements of the slit diaphragm complex identified the nephrin model in the promoter region of zonula occludens-1 (ZO-1). Genome-wide scans using this promoter model effectively predicted a previously unrecognized slit diaphragm molecule, cadherin-5. Nephrin, ZO-1, and cadherin-5 mRNA showed stringent coexpression across a diverse set of human glomerular diseases. Comparative promoter analysis can identify regulatory pathways at work in tissue homeostasis and disease processes.

  11. MicroRNA-31 negatively regulates peripherally derived regulatory T-cell generation by repressing retinoic acid-inducible protein 3

    PubMed Central

    Zhang, Lingyun; Ke, Fang; Liu, Zhaoyuan; Bai, Jing; Liu, Jinlin; Yan, Sha; Xu, Zhenyao; Lou, Fangzhou; Wang, Hong; Zhu, Huiyuan; Sun, Yang; Cai, Wei; Gao, Yuanyuan; Li, Qun; Yu, Xue-Zhong; Qian, Youcun; Hua, Zichun; Deng, Jiong; Li, Qi-Jing; Wang, Honglin

    2015-01-01

    Peripherally derived regulatory T (pTreg) cell generation requires T-cell receptor (TCR) signalling and the cytokines TGF-β1 and IL-2. Here we show that TCR signalling induces the microRNA miR-31, which negatively regulates pTreg-cell generation. miR-31 conditional deletion results in enhanced induction of pTreg cells, and decreased severity of experimental autoimmune encephalomyelitis (EAE). Unexpectedly, we identify Gprc5a as a direct target of miR-31. Gprc5a is known as retinoic acid-inducible protein 3, and its deficiency leads to impaired pTreg-cell induction and increased EAE severity. By generating miR-31 and Gprc5a double knockout mice, we show that miR-31 promotes the development of EAE through inhibiting Gprc5a. Thus, our data identify miR-31 and its target Gprc5a as critical regulators for pTreg-cell generation, suggesting a previously unrecognized epigenetic mechanism for dysfunctional Treg cells in autoimmune diseases. PMID:26165721

  12. Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

    PubMed Central

    Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

    2016-01-01

    The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. DOI: http://dx.doi.org/10.7554/eLife.14277.001 PMID:27240166

  13. Commensal bacterial–derived signals regulate basophil hematopoiesis and allergic inflammation

    PubMed Central

    Hill, David A.; Siracusa, Mark C.; Abt, Michael C.; Kim, Brian S.; Kobuley, Dmytro; Kubo, Masato; Kambayashi, Taku; LaRosa, David F.; Renner, Ellen D.; Orange, Jordan S.; Bushman, Frederic D.; Artis, David

    2012-01-01

    Commensal bacteria that colonize mammalian barrier surfaces are reported to influence T helper type 2 (TH2) cytokine–dependent inflammation and susceptibility to allergic disease, although the mechanisms that underlie these observations are poorly understood. In this report, we identify that deliberate alteration of commensal bacterial populations via oral antibiotic treatment resulted in elevated serum immunoglobulin E (IgE) levels, increased steady–state circulating basophil populations, and exaggerated basophil–mediated TH2 cell responses and allergic inflammation. Elevated serum IgE levels correlated with increased circulating basophil populations in mice and subjects with hyperimmunoglobulinemia E syndrome. Furthermore, B cell–intrinsic expression of MyD88 was required to limit serum IgE levels and circulating basophil populations in mice. Commensal–derived signals were found to influence basophil development by limiting proliferation of bone marrow–resident precursor populations. Collectively, these results identify a previously unrecognized pathway through which commensal–derived signals influence basophil hematopoiesis and susceptibility to TH2 cytokine–dependent inflammation and allergic disease. PMID:22447074

  14. Isolation of carbohydrate-metabolizing, extremely halophilic bacteria.

    NASA Technical Reports Server (NTRS)

    Tomlinson, G. A.; Hochstein, L. I.

    1972-01-01

    Four previously unrecognized strains of extremely halophilic bacteria that utilize carbohydrates have been isolated. Gas production proved an unreliable index of carbohydrate metabolism; therefore, carbohydrate utilization was measured by determining acid formation and sugar disappearance during growth. By these procedures, carbohydrate utilization was readily detected. The results suggest that carbohydrate dissimilation by extremely halophilic bacteria may be more common than previously thought and that the apparent rarity of carbohydrate-metabolizing halophiles may be an artifact of the isolation procedures used.

  15. Screening for Albuminuria Identifies Individuals at Increased Renal Risk

    PubMed Central

    van der Velde, Marije; Halbesma, Nynke; de Charro, Frank T.; Bakker, Stephan J.L.; de Zeeuw, Dick; de Jong, Paul E.; Gansevoort, Ronald T.

    2009-01-01

    It is unknown whether screening for albuminuria in the general population identifies individuals at increased risk for renal replacement therapy (RRT) or accelerated loss of renal function. Here, in a general population-based cohort of 40,854 individuals aged 28 to 75 yr, we collected a first morning void for measurement of urinary albumin. In a subset of 6879 individuals, we measured 24-h urinary albumin excretion and estimated GFR at baseline and during 6 yr of follow-up. Linkage with the national RRT registry identified 45 individuals who started RRT during 9 yr of follow-up. The quantity of albuminuria was associated with increased renal risk: the higher the level of albuminuria, the higher the risk of need for renal replacement therapy and the more rapid renal function decline. A urinary albumin concentration of ≥20 mg/L identified individuals who started RRT during follow-up with 58% sensitivity and 92% specificity. Of the identified individuals, 39% were previously unknown to have impaired renal function, and 50% were not being medically treated. Restricting screening to high-risk groups (e.g., known hypertension, diabetes, cardiovascular disease [CVD], older age) reduced the sensitivity of the test only marginally but failed to identify 45% of individuals with micro- and macroalbuminuria. In conclusion, individuals with elevated levels of urinary albumin are at increased risk for RRT and accelerated loss of renal function. Screening for albuminuria identifies patients at increased risk for progressive renal disease, 40 to 50% of whom were previously undiagnosed or untreated. PMID:19211710

  16. The hypertensive response to intubation. Do researchers acknowledge previous work?

    PubMed

    Smith, A J; Goodman, N W

    1997-01-01

    To see whether investigators of a circumscribed research topic, the haemodynamic response to orotracheal intubation, review and cite previous work. A 1989 editorial about the response was critical to investigators for measuring physiology but not outcome; for nonetheless making recommendations; for studying only patients not at risk; and for implying patients are at risk when this is not certain. A systemic Medline search was made for English language reports published during or after 1990, and their citation lists read for missed reports. All retrieved papers were read for citation of the editorial and for acknowledgement of its criticisms. Citations were tabulated, and cross-referenced between papers, to see whether blocks of citations had been obtained from other investigators' reports. Eighty-one full reports, from 48 groups of investigators, were obtained. The 1989 editorial was cited twice. All studies included physiological measurements, but none reported long-term outcome. There was no comment on the need to know outcome in 39 reports. Pre-existing risk factors were exclusions in 65 studies. In 56 papers, complications of the response were given as the reason for the study; in 41 of these papers only healthy subjects were studied. In total, 249 references about the response were identified from the 81 papers. There was no obvious evidence that citations were obtained from others' papers. Recognised deficiencies in research method were not acknowledged. When submitting work for publication, investigators should provide evidence of how they searched for previous work.

  17. Previous blood pressure measurement and associated factors in student adolescents

    PubMed Central

    Magalhães, Marina Gabriella Pereira de Andrada; Farah, Breno Quintella; de Barros, Mauro Virgilio Gomes; Ritti-Dias, Raphael Mendes

    2015-01-01

    Objective To identify prevalence of previous blood pressure measurement and analyze some associated factors in adolescents. Methods This cross-sectional study included 6,077 adolescents aged 14 to 19 years. Demographic characteristics included (sex, age, period of study, region of residence, work, skin color, and economic) status, history of blood pressure measurement within last 12 months, local of blood pressure measurement, and reading obtained. To assess associations between previous blood pressure measurement with demographic characteristics and high blood pressure we used descriptive statistics and logistic regression analysis. Results Out of the adolescents, 56.8% reported no blood pressure measurement within the last 12 months. The health centers and the physician’s office were most mentioned places for blood pressure measurement (28.3% and 36.9%, respectively). Boys (odds ratio of 1.64 95%CI: 1.46-1.84) aged 14 to 16 years (odds ratio of 1.12; 95%CI: 1.01-1.25), whose economic status was unfavorable (odds ratio of 1.48; 95%CI: 1.32-1.67) were significantly associated with no blood pressure measurement. Working was a protective factor for was not blood pressure measurement (odds ratio of 0.84; 95%CI: 0.73-0.97). Conclusion Most of adolescents did not have their blood pressure measured within the last 12 months. Boys aged 14 to 16 years and those with unfavorable economic status had higher chance of not having their blood pressure measured. PMID:26466061

  18. Determining root correspondence between previously and newly detected objects

    DOEpatents

    Paglieroni, David W.; Beer, N Reginald

    2014-06-17

    A system that applies attribute and topology based change detection to networks of objects that were detected on previous scans of a structure, roadway, or area of interest. The attributes capture properties or characteristics of the previously detected objects, such as location, time of detection, size, elongation, orientation, etc. The topology of the network of previously detected objects is maintained in a constellation database that stores attributes of previously detected objects and implicitly captures the geometrical structure of the network. A change detection system detects change by comparing the attributes and topology of new objects detected on the latest scan to the constellation database of previously detected objects.

  19. A national plan for assisting states, federal agencies, and tribes in managing white-nose syndrome in bats

    USGS Publications Warehouse

    ,; ,; ,; ,; ,; ,; ,; ,; ,; ,; ,; ,; ,; ,

    2011-01-01

    White-nose syndrome (WNS) is a disease responsible for unprecedented mortality in hibernating bats in the northeastern U.S. This previously unrecognized disease has spread very rapidly since its discovery in January 2007, and poses a considerable threat to hibernating bats throughout North America. As WNS spreads, the challenges for understanding and managing the disease continue to increase. Given the escalating complexity of these challenges, a highly coordinated effort is required for State, Federal, and Tribal wildlife agencies, and private partners to respond effectively to WNS and conserve species of bats. The plan proposed herein details the elements that are critical to the investigation and management of WNS, identifies key action items to address stated goals, and outlines the role(s) of agencies and entities involved in this continental effort.

  20. Optimized knock-in of point mutations in zebrafish using CRISPR/Cas9.

    PubMed

    Prykhozhij, Sergey V; Fuller, Charlotte; Steele, Shelby L; Veinotte, Chansey J; Razaghi, Babak; Robitaille, Johane M; McMaster, Christopher R; Shlien, Adam; Malkin, David; Berman, Jason N

    2018-06-14

    We have optimized point mutation knock-ins into zebrafish genomic sites using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 reagents and single-stranded oligodeoxynucleotides. The efficiency of knock-ins was assessed by a novel application of allele-specific polymerase chain reaction and confirmed by high-throughput sequencing. Anti-sense asymmetric oligo design was found to be the most successful optimization strategy. However, cut site proximity to the mutation and phosphorothioate oligo modifications also greatly improved knock-in efficiency. A previously unrecognized risk of off-target trans knock-ins was identified that we obviated through the development of a workflow for correct knock-in detection. Together these strategies greatly facilitate the study of human genetic diseases in zebrafish, with additional applicability to enhance CRISPR-based approaches in other animal model systems.

  1. Crossing Thresholds: Identifying Conceptual Transitions in Postsecondary Teaching

    ERIC Educational Resources Information Center

    Wilcox, Susan; Leger, Andy B.

    2013-01-01

    In this paper we report on research we conducted to begin the process of identifying threshold concepts in the field of postsecondary teaching. Meyer & Land (2006) propose that within all disciplinary fields there seem to be particular "threshold concepts" that serve as gateways, opening up new and previously inaccessible ways of…

  2. 76 FR 19721 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    ... Services GmbH (Type Certificate Previously Held by AvCraft Aerospace GmbH; Fairchild Dornier GmbH; Dornier Luftfahrt GmbH) Model 328-100 and -300 Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... information identified in this proposed AD, contact 328 Support Services GmbH, Global Support Center, P.O. Box...

  3. 75 FR 42487 - Supplementary Identifying Information of Previously-Designated Individual, Foreign Narcotics...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-21

    ... Director, Compliance Outreach & Implementation, Office of Foreign Assets Control, Department of the... their businesses and agents access to the U.S. financial system and the benefits of trade and..., the Director of the Central Intelligence Agency, the Director of the Federal Bureau of Investigation...

  4. Urinary tract infections in hospital pediatrics: many previous antibiotherapy and antibiotics resistance, including fluoroquinolones.

    PubMed

    Garraffo, A; Marguet, C; Checoury, A; Boyer, S; Gardrat, A; Houivet, E; Caron, F

    2014-02-01

    We studied antibiotic resistance in pediatric UTIs and we evaluated the impact of antibiotic exposure in the previous 12 months, very little French data being available for this population. We conducted a multicenter prospective study including children consulting for, or admitted in 2 hospitals. Prior antibiotic exposure was documented from their health record. One hundred and ten patients (73 girls), 11 days to 12 years of age, were included in 10 months. Ninety-six percent presented with pyelonephritis, associated to uropathy for 25%. Escherichia coli was predominant (78%), followed by Proteus spp. and Enterococcus spp. The antibiotic resistance rate of E. coli was high and close to that reported for adults with complicated UTIs: amoxicillin 60%, amoxicillin-clavulanate 35%, cefotaxim 5%, trimethoprim-sulfametoxazole 26%, nalidixic acid 9%, ciprofloxacin 7%, gentamycin 1%, nitrofurantoin and fosfomycin 0%. The antibiotic exposure in the previous 12 months involved 62 children (56%) most frequently with β-lactams (89%) for a respiratory tract infection (56%). A clear relationship between exposure and resistance was observed for amoxicillin (71% vs. 46%), first generation (65% vs. 46%) and third generation (9% vs. 3%) cephalosporins, or trimethoprim-sulfamethoxazole (36% vs. 15%). However, antibiotic exposure could not account alone for the results, as suggested by the 7% of ciprofloxacin resistance, observed without any identified previous treatment. Bacterial species and antibiotic resistance level in children are similar to those reported for adults. Antibiotic exposure in the previous 12 months increases the risk of resistance but other factors are involved (previous antibiotic therapies and fecal-oral or mother-to-child transmission). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Adult pertussis is unrecognized public health problem in Thailand.

    PubMed

    Siriyakorn, Nirada; Leethong, Pornvimol; Tantawichien, Terapong; Sripakdee, Saowalak; Kerdsin, Anusak; Dejsirilert, Surang; Paitoonpong, Leilani

    2016-01-25

    Although pertussis has been considered a disease of childhood, it is also recognized as an important respiratory tract infection in adolescents and adults. However, in countries with routine vaccination against pertussis with high coverage, pertussis is not usually taken into consideration for the etiology of prolonged cough in adults. Previous studies in a variety of populations in developed countries have documented that pertussis is quite common, ranging from 2.9 to 32% of adolescents and adults with prolonged cough. The anticipation and early recognition of this change in the epidemiology is important because the affected adolescents and adults act as reservoirs of the disease and source of infection to the vulnerable population of infants, for whom the disease can be life threatening. We conducted a prospective study to determine the prevalence of pertussis in Thai adults with prolonged cough. Seventy-six adult patients with a cough lasting for more than 2 weeks (range, 14-180 days) were included in the present study. The data regarding medical history and physical examination were carefully analyzed. Nasopharyngeal swabs from all patients were obtained for the detection of deoxyribonucleic acid of Bordetella pertussis by the polymerase chain reaction (PCR) method. Paired serum samples were collected and tested for IgG antibody against pertussis toxin by using an ELISA method. Of 76 adult patients, 14 patients (18.4%) with the mean age of 59 (range, 28-85) years and the mean duration of cough of 34 (range, 14-120) days had laboratory evidence of acute pertussis infection. One patient was diagnosed by the PCR method, while the rest had serological diagnosis. Whooping cough is a significantly associated symptom of patients with chronic cough who had laboratory evidence of pertussis. (p < .05, odds ratio 3.75, 95% confidence interval: 1.00, 14.06) CONCLUSION: Pertussis is being increasingly recognized as a cause of prolonged, distressing cough among adults in

  6. Personality Characteristics of Leaders Identifying with Different Student Subcultures.

    ERIC Educational Resources Information Center

    Brainard, Stephen R.

    This study was conducted to discover differences in personality characteristics among student leaders. The personality characteristics of presidents of campus organizations affiliated with one of four distinguishable student subcultures, identified by previous research as vocational, academic, collegiate, and nonconformist, were measured by the…

  7. Natural History of Ground-Glass Lesions Among Patients With Previous Lung Cancer.

    PubMed

    Shewale, Jitesh B; Nelson, David B; Rice, David C; Sepesi, Boris; Hofstetter, Wayne L; Mehran, Reza J; Vaporciyan, Ara A; Walsh, Garrett L; Swisher, Stephen G; Roth, Jack A; Antonoff, Mara B

    2018-06-01

    Among patients with previous lung cancer, the malignant potential of subsequent ground-glass opacities (GGOs) on computed tomography remains unknown, with a lack of consensus regarding surveillance and intervention. This study sought to describe the natural history of GGO in patients with a history of lung cancer. A retrospective review was performed of 210 patients with a history of lung cancer and ensuing computed tomography evidence of pure or mixed GGOs between 2007 and 2013. Computed tomography reports were reviewed to determine the fate of the GGOs, by classifying all lesions as stable, resolved, or progressive over the course of the study. Multivariable analysis was performed to identify predictors of GGO progression and resolution. The mean follow-up time was 13 months. During this period, 55 (26%) patients' GGOs were stable, 131 (62%) resolved, and 24 (11%) progressed. Of the 24 GGOs that progressed, three were subsequently diagnosed as adenocarcinoma. Patients of black race (odds ratio [OR], 0.26) and other races besides white (OR, 0.89) had smaller odds of GGO resolution (p = 0.033), whereas patients with previous lung squamous cell carcinoma (OR, 5.16) or small cell carcinoma (OR, 5.36) were more likely to experience GGO resolution (p < 0.001). On multivariable analysis, only a history of adenocarcinoma was an independent predictor of GGO progression (OR, 6.9; p = 0.011). Among patients with a history of lung cancer, prior adenocarcinoma emerged as a predictor of GGO progression, whereas a history of squamous cell carcinoma or small cell carcinoma and white race were identified as predictors of GGO resolution. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  8. 49 CFR 236.1031 - Previously approved PTC systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Previously approved PTC systems. 236.1031 Section 236.1031 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD....1005 and 236.1007 and otherwise conform to this subpart. (d) Previous approval or recognition of a...

  9. Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus

    PubMed Central

    Moon, Joon Ho; Kwak, Soo Heon; Jang, Hak C.

    2017-01-01

    Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is characterized by underlying maternal defects in the β-cell response to insulin during pregnancy. Women with a previous history of GDM have a greater than 7-fold higher risk of developing postpartum diabetes compared with women without GDM. Various risk factors for postpartum diabetes have been identified, including maternal age, glucose levels in pregnancy, family history of diabetes, pre-pregnancy and postpartum body mass index, dietary patterns, physical activity, and breastfeeding. Genetic studies revealed that GDM shares common genetic variants with type 2 diabetes. A number of lifestyle interventional trials that aimed to ameliorate modifiable risk factors, including diet, exercise, and breastfeeding, succeeded in reducing the incidence of postpartum diabetes, weight retention, and other obesity-related morbidities. The present review summarizes the findings of previous studies on the incidence and risk factors of postpartum diabetes and discusses recent lifestyle interventional trials that attempted to prevent postpartum diabetes. PMID:28049284

  10. Neuro-Immune Mechanisms in Response to Venezuelan equine encephalitis Virus Infection

    DTIC Science & Technology

    2000-05-01

    horses . They were subsequently shown to be previously unrecognized viral agents of severe equine encephalitis (Smith et al., 1997). One member of...iii ABSTRACT NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION Major Bruce A. Schoneboom directed by Franziska B...Grieder, DVM, Ph.D., Assistant Professor of Microbiology and Immunology, Molecular and Cellular Biology, and Neuroscience Venezuelan equine

  11. Citation of previous meta-analyses on the same topic: a clue to perpetuation of incorrect methods?

    PubMed

    Li, Tianjing; Dickersin, Kay

    2013-06-01

    Systematic reviews and meta-analyses serve as a basis for decision-making and clinical practice guidelines and should be carried out using appropriate methodology to avoid incorrect inferences. We describe the characteristics, statistical methods used for meta-analyses, and citation patterns of all 21 glaucoma systematic reviews we identified pertaining to the effectiveness of prostaglandin analog eye drops in treating primary open-angle glaucoma, published between December 2000 and February 2012. We abstracted data, assessed whether appropriate statistical methods were applied in meta-analyses, and examined citation patterns of included reviews. We identified two forms of problematic statistical analyses in 9 of the 21 systematic reviews examined. Except in 1 case, none of the 9 reviews that used incorrect statistical methods cited a previously published review that used appropriate methods. Reviews that used incorrect methods were cited 2.6 times more often than reviews that used appropriate statistical methods. We speculate that by emulating the statistical methodology of previous systematic reviews, systematic review authors may have perpetuated incorrect approaches to meta-analysis. The use of incorrect statistical methods, perhaps through emulating methods described in previous research, calls conclusions of systematic reviews into question and may lead to inappropriate patient care. We urge systematic review authors and journal editors to seek the advice of experienced statisticians before undertaking or accepting for publication a systematic review and meta-analysis. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  12. 44 CFR 402.5 - Forwarding commodities previously shipped.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... previously shipped. 402.5 Section 402.5 Emergency Management and Assistance DEPARTMENT OF COMMERCE AND DEPARTMENT OF TRANSPORTATION SHIPMENTS ON AMERICAN FLAG SHIPS AND AIRCRAFT (T-1, INT. 1) § 402.5 Forwarding commodities previously shipped. Order T-1 applies to transportation on or discharge from ships documented...

  13. 44 CFR 402.5 - Forwarding commodities previously shipped.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... previously shipped. 402.5 Section 402.5 Emergency Management and Assistance DEPARTMENT OF COMMERCE AND DEPARTMENT OF TRANSPORTATION SHIPMENTS ON AMERICAN FLAG SHIPS AND AIRCRAFT (T-1, INT. 1) § 402.5 Forwarding commodities previously shipped. Order T-1 applies to transportation on or discharge from ships documented...

  14. 44 CFR 402.5 - Forwarding commodities previously shipped.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... previously shipped. 402.5 Section 402.5 Emergency Management and Assistance DEPARTMENT OF COMMERCE AND DEPARTMENT OF TRANSPORTATION SHIPMENTS ON AMERICAN FLAG SHIPS AND AIRCRAFT (T-1, INT. 1) § 402.5 Forwarding commodities previously shipped. Order T-1 applies to transportation on or discharge from ships documented...

  15. 44 CFR 402.5 - Forwarding commodities previously shipped.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... previously shipped. 402.5 Section 402.5 Emergency Management and Assistance DEPARTMENT OF COMMERCE AND DEPARTMENT OF TRANSPORTATION SHIPMENTS ON AMERICAN FLAG SHIPS AND AIRCRAFT (T-1, INT. 1) § 402.5 Forwarding commodities previously shipped. Order T-1 applies to transportation on or discharge from ships documented...

  16. CPTAC Releases Largest-Ever Breast Cancer Proteome Dataset from Previously Genome Characterized Tumors | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) scientists have released a dataset of proteins and  phosphopeptides identified through deep proteomic and phosphoproteomic analysis of breast tumor samples, previously genomically analyzed by The Cancer Genome Atlas (TCGA).

  17. [Meningitis and white matter lesions due to Streptococcus mitis in a previously healthy child].

    PubMed

    Yiş, Reyhan; Yüksel, Ciğdem Nükhet; Derundere, Umit; Yiş, Uluç

    2011-10-01

    Streptococcus mitis, an important member of viridans streptococci, is found in the normal flora of the oropharynx, gastrointestinal tract, female genital tract and skin. Although it is of low pathogenicity and virulence, it may cause serious infections in immunocompromised patients. Meningitis caused by S.mitis has been described in patients with previous spinal anesthesia, neurosurgical procedure, malignancy, bacterial endocarditis with neurological complications and alcoholics, but it is rare in patients who are previously healthy. In this report, a rare case of meningoencephalitis caused by S.mitis developed in a previously healthy child has been presented. A previously healthy eight-year-old girl who presented with fever, altered state of consciousness, and headache was hospitalized in intensive care unit with the diagnosis of meningitis. Past history revealed that she was treated with amoxicillin-clavulanate for acute sinusitis ten days before her admission. Whole blood count revealed the followings: hemoglobin 13 g/dl, white blood cell count 18.6 x 109/L (90% neutrophils), platelet count 200 x 109/L and 150 leucocytes were detected on cerebrospinal fluid (CSF) examination. Protein and glucose levels of CSF were 80 mg/dl and 40 mg/dl (concomitant blood glucose 100 mg/dl), respectively. Brain magnetic resonance imaging (MRI) revealed widespread white matter lesions, and alpha-hemolytic streptococci were grown in CSF culture. The isolate was identified as S.mitis with conventional methods, and also confirmed by VITEK2 (bioMerieux, France) and API 20 STREP (bioMerieux, France) systems. Isolate was found susceptible to penicillin, erythromycin, clindamycin, tetracycline, cefotaxime, vancomycin and chloramphenicol. Regarding the etiology, echocardiography revealed no vegetation nor valve pathology, and peripheral blood smear showed no abnormality. Immunoglobulin and complement levels were within normal limits. Ongoing inflammation in maxillary sinuses detected in

  18. 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

    PubMed Central

    Gorski, Mathias; van der Most, Peter J.; Teumer, Alexander; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Nolte, Ilja M.; Cocca, Massimiliano; Taliun, Daniel; Gomez, Felicia; Li, Yong; Tayo, Bamidele; Tin, Adrienne; Feitosa, Mary F.; Aspelund, Thor; Attia, John; Biffar, Reiner; Bochud, Murielle; Boerwinkle, Eric; Borecki, Ingrid; Bottinger, Erwin P.; Chen, Ming-Huei; Chouraki, Vincent; Ciullo, Marina; Coresh, Josef; Cornelis, Marilyn C.; Curhan, Gary C.; d’Adamo, Adamo Pio; Dehghan, Abbas; Dengler, Laura; Ding, Jingzhong; Eiriksdottir, Gudny; Endlich, Karlhans; Enroth, Stefan; Esko, Tõnu; Franco, Oscar H.; Gasparini, Paolo; Gieger, Christian; Girotto, Giorgia; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Hancock, Stephen J.; Harris, Tamara B.; Helmer, Catherine; Höllerer, Simon; Hofer, Edith; Hofman, Albert; Holliday, Elizabeth G.; Homuth, Georg; Hu, Frank B.; Huth, Cornelia; Hutri-Kähönen, Nina; Hwang, Shih-Jen; Imboden, Medea; Johansson, Åsa; Kähönen, Mika; König, Wolfgang; Kramer, Holly; Krämer, Bernhard K.; Kumar, Ashish; Kutalik, Zoltan; Lambert, Jean-Charles; Launer, Lenore J.; Lehtimäki, Terho; de Borst, Martin; Navis, Gerjan; Swertz, Morris; Liu, Yongmei; Lohman, Kurt; Loos, Ruth J. F.; Lu, Yingchang; Lyytikäinen, Leo-Pekka; McEvoy, Mark A.; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Metzger, Marie; Mihailov, Evelin; Mitchell, Paul; Nauck, Matthias; Oldehinkel, Albertine J.; Olden, Matthias; WJH Penninx, Brenda; Pistis, Giorgio; Pramstaller, Peter P.; Probst-Hensch, Nicole; Raitakari, Olli T.; Rettig, Rainer; Ridker, Paul M.; Rivadeneira, Fernando; Robino, Antonietta; Rosas, Sylvia E.; Ruderfer, Douglas; Ruggiero, Daniela; Saba, Yasaman; Sala, Cinzia; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J.; Sedaghat, Sanaz; Smith, Albert V.; Sorice, Rossella; Stengel, Benedicte; Stracke, Sylvia; Strauch, Konstantin; Toniolo, Daniela; Uitterlinden, Andre G.; Ulivi, Sheila; Viikari, Jorma S.; Völker, Uwe; Vollenweider, Peter; Völzke, Henry; Vuckovic, Dragana; Waldenberger, Melanie; Jin Wang, Jie; Yang, Qiong; Chasman, Daniel I.; Tromp, Gerard; Snieder, Harold; Heid, Iris M.; Fox, Caroline S.; Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian

    2017-01-01

    HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples. PMID:28452372

  19. 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

    PubMed

    Gorski, Mathias; van der Most, Peter J; Teumer, Alexander; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Nolte, Ilja M; Cocca, Massimiliano; Taliun, Daniel; Gomez, Felicia; Li, Yong; Tayo, Bamidele; Tin, Adrienne; Feitosa, Mary F; Aspelund, Thor; Attia, John; Biffar, Reiner; Bochud, Murielle; Boerwinkle, Eric; Borecki, Ingrid; Bottinger, Erwin P; Chen, Ming-Huei; Chouraki, Vincent; Ciullo, Marina; Coresh, Josef; Cornelis, Marilyn C; Curhan, Gary C; d'Adamo, Adamo Pio; Dehghan, Abbas; Dengler, Laura; Ding, Jingzhong; Eiriksdottir, Gudny; Endlich, Karlhans; Enroth, Stefan; Esko, Tõnu; Franco, Oscar H; Gasparini, Paolo; Gieger, Christian; Girotto, Giorgia; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Hancock, Stephen J; Harris, Tamara B; Helmer, Catherine; Höllerer, Simon; Hofer, Edith; Hofman, Albert; Holliday, Elizabeth G; Homuth, Georg; Hu, Frank B; Huth, Cornelia; Hutri-Kähönen, Nina; Hwang, Shih-Jen; Imboden, Medea; Johansson, Åsa; Kähönen, Mika; König, Wolfgang; Kramer, Holly; Krämer, Bernhard K; Kumar, Ashish; Kutalik, Zoltan; Lambert, Jean-Charles; Launer, Lenore J; Lehtimäki, Terho; de Borst, Martin; Navis, Gerjan; Swertz, Morris; Liu, Yongmei; Lohman, Kurt; Loos, Ruth J F; Lu, Yingchang; Lyytikäinen, Leo-Pekka; McEvoy, Mark A; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Metzger, Marie; Mihailov, Evelin; Mitchell, Paul; Nauck, Matthias; Oldehinkel, Albertine J; Olden, Matthias; Wjh Penninx, Brenda; Pistis, Giorgio; Pramstaller, Peter P; Probst-Hensch, Nicole; Raitakari, Olli T; Rettig, Rainer; Ridker, Paul M; Rivadeneira, Fernando; Robino, Antonietta; Rosas, Sylvia E; Ruderfer, Douglas; Ruggiero, Daniela; Saba, Yasaman; Sala, Cinzia; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J; Sedaghat, Sanaz; Smith, Albert V; Sorice, Rossella; Stengel, Benedicte; Stracke, Sylvia; Strauch, Konstantin; Toniolo, Daniela; Uitterlinden, Andre G; Ulivi, Sheila; Viikari, Jorma S; Völker, Uwe; Vollenweider, Peter; Völzke, Henry; Vuckovic, Dragana; Waldenberger, Melanie; Jin Wang, Jie; Yang, Qiong; Chasman, Daniel I; Tromp, Gerard; Snieder, Harold; Heid, Iris M; Fox, Caroline S; Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A; Fuchsberger, Christian

    2017-04-28

    HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10 -8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.

  20. Genetically distinct genogroup IV norovirus strains identified in wastewater.

    PubMed

    Kitajima, Masaaki; Rachmadi, Andri T; Iker, Brandon C; Haramoto, Eiji; Gerba, Charles P

    2016-12-01

    We investigated the prevalence and genetic diversity of genogroup IV norovirus (GIV NoV) strains in wastewater in Arizona, United States, over a 13-month period. Among 50 wastewater samples tested, GIV NoVs were identified in 13 (26 %) of the samples. A total of 47 different GIV NoV strains were identified, which were classified into two genetically distinct clusters: the GIV.1 human cluster and a unique genetic cluster closely related to strains previously identified in Japanese wastewater. The results provide additional evidence of the considerable genetic diversity among GIV NoV strains through the analysis of wastewater containing virus strains shed from all populations.

  1. Myeloproliferative neoplasms in five multiple sclerosis patients☆

    PubMed Central

    Thorsteinsdottir, Sigrun; Bjerrum, Ole Weis; Hasselbalch, Hans Carl

    2013-01-01

    The concurrence of myeloproliferative neoplasms (MPNs) and multiple sclerosis (MS) is unusual. We report five patients from a localized geographic area in Denmark with both MS and MPN; all the patients were diagnosed with MPNs in the years 2007–2012. We describe the patients' history and treatment. A potential link between MS and MPNs has not been previously recognized. This observation calls attention to potential environmental factors and/or previously unrecognized genetic factors predisposing these patients to both MS and MPNs. PMID:24371783

  2. Flank vents and graben as indicators of Late Amazonian volcanotectonic activity on Olympus Mons

    NASA Astrophysics Data System (ADS)

    Peters, S. I.; Christensen, P. R.

    2017-03-01

    Previous studies have focused on large-scale features on Olympus Mons, such as its flank terraces, the summit caldera complex, and the basal escarpment and aureole deposits. Here we identify and characterize previously unrecognized and unmapped small scale features to help further understand the volcanotectonic evolution of this enormous volcano. Using Context Camera, High Resolution Imaging Science Experiment, Thermal Emission Imaging System, High Resolution Stereo Camera Digital Terrain Model, and Mars Orbiter Laser Altimeter data, we identified and characterized the morphology and distribution of 60 flank vents and 84 grabens on Olympus Mons. We find that effusive eruptions have dominated volcanic activity on Olympus Mons in the Late Amazonian. Explosive eruptions were rare, implying volatile-poor magmas and/or a lack of magma-water interactions during the Late Amazonian. The distribution of flank vents suggests dike propagation of hundreds of kilometers and shallow magma storage. Small grabens, not previously observed in lower-resolution data, occur primarily on the lower flanks of Olympus Mons and indicate late-stage extensional tectonism. Based on superposition relationships, we have concluded two stages of development for Olympus Mons during the Late Amazonian: (1) primarily effusive resurfacing and formation of flank vents followed by (2) waning effusive volcanism and graben formation and/or reactivation. This developmental sequence resembles that proposed for Ascraeus Mons and other large Martian shields, suggesting a similar geologic evolution for these volcanoes.

  3. 2 CFR 225.45 - Relationship to previous issuance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false Relationship to previous issuance. 225.45 Section 225.45 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements... INDIAN TRIBAL GOVERNMENTS (OMB CIRCULAR A-87) § 225.45 Relationship to previous issuance. (a) The...

  4. 2 CFR 230.45 - Relationship to previous issuance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Relationship to previous issuance. 230.45 Section 230.45 Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET CIRCULARS AND GUIDANCE Reserved COST PRINCIPLES FOR NON-PROFIT ORGANIZATIONS (OMB CIRCULAR A-122) § 230.45 Relationship to previous issuance. (a...

  5. Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa

    PubMed Central

    Folarin, Onikepe A.; Grove, Jessica N.; Odia, Ikponmwonsa; Ehiane, Philomena E.; Omoniwa, Omowunmi; Omoregie, Omigie; Jiang, Pan-Pan; Yozwiak, Nathan L.; Matranga, Christian B.; Yang, Xiao; Gire, Stephen K.; Winnicki, Sarah; Tariyal, Ridhi; Schaffner, Stephen F.; Okokhere, Peter O.; Okogbenin, Sylvanus; Akpede, George O.; Asogun, Danny A.; Agbonlahor, Dennis E.; Walker, Peter J.; Tesh, Robert B.; Levin, Joshua Z.; Garry, Robert F.; Sabeti, Pardis C.; Happi, Christian T.

    2015-01-01

    Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease

  6. Detection of mumps virus genotype H in two previously vaccinated patients from Mexico City.

    PubMed

    Del Valle, Alberto; García, Alí A; Barrón, Blanca L

    2016-06-01

    Infections caused by mumps virus (MuV) have been successfully prevented through vaccination; however, in recent years, an increasing number of mumps outbreaks have been reported within vaccinated populations. In this study, MuV was genotyped for the first time in Mexico. Saliva samples were obtained from two previously vaccinated patients in Mexico City who had developed parotitis. Viral isolation was carried out in Vero cells, and the SH and HN genes were amplified by RT-PCR. Amplicons were sequenced and compared to a set of reference sequences to identify the MuV genotype.

  7. A recellularized human colon model identifies cancer driver genes

    PubMed Central

    Chen, Huanhuan Joyce; Wei, Zhubo; Sun, Jian; Bhattacharya, Asmita; Savage, David J; Serda, Rita; Mackeyev, Yuri; Curley, Steven A.; Bu, Pengcheng; Wang, Lihua; Chen, Shuibing; Cohen-Gould, Leona; Huang, Emina; Shen, Xiling; Lipkin, Steven M.; Copeland, Neal G.; Jenkins, Nancy A.; Shuler, Michael L.

    2016-01-01

    Refined cancer models are needed to bridge the gap between cell-line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell-populated mucosa and an intact muscularis mucosa layer. This ex vivo system recapitulates the pathophysiological progression from APC-mutant neoplasia to submucosal invasive tumor. We used it to perform a Sleeping Beauty transposon mutagenesis screen to identify genes that cooperate with mutant APC in driving invasive neoplasia. 38 candidate invasion driver genes were identified, 17 of which have been previously implicated in colorectal cancer progression, including TCF7L2, TWIST2, MSH2, DCC and EPHB1/2. Six invasion driver genes that to our knowledge have not been previously described were validated in vitro using cell proliferation, migration and invasion assays, and ex vivo using recellularized human colon. These results demonstrate the utility of our organoid model for studying cancer biology. PMID:27398792

  8. Common Viral Integration Sites Identified in Avian Leukosis Virus-Induced B-Cell Lymphomas

    PubMed Central

    Justice, James F.; Morgan, Robin W.

    2015-01-01

    ABSTRACT Avian leukosis virus (ALV) induces B-cell lymphoma and other neoplasms in chickens by integrating within or near cancer genes and perturbing their expression. Four genes—MYC, MYB, Mir-155, and TERT—have previously been identified as common integration sites in these virus-induced lymphomas and are thought to play a causal role in tumorigenesis. In this study, we employ high-throughput sequencing to identify additional genes driving tumorigenesis in ALV-induced B-cell lymphomas. In addition to the four genes implicated previously, we identify other genes as common integration sites, including TNFRSF1A, MEF2C, CTDSPL, TAB2, RUNX1, MLL5, CXorf57, and BACH2. We also analyze the genome-wide ALV integration landscape in vivo and find increased frequency of ALV integration near transcriptional start sites and within transcripts. Previous work has shown ALV prefers a weak consensus sequence for integration in cultured human cells. We confirm this consensus sequence for ALV integration in vivo in the chicken genome. PMID:26670384

  9. 2 CFR 1.215 - Relationship to previous issuances.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 2 Grants and Agreements 1 2013-01-01 2013-01-01 false Relationship to previous issuances. 1.215... ABOUT TITLE 2 OF THE CODE OF FEDERAL REGULATIONS AND SUBTITLE A Introduction toSubtitle A § 1.215... title 2 of the CFR. Specifically: Guidance in * * * On * * * Previously was in * * * (a) Chapter I, part...

  10. 2 CFR 1.215 - Relationship to previous issuances.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Relationship to previous issuances. 1.215... ABOUT TITLE 2 OF THE CODE OF FEDERAL REGULATIONS AND SUBTITLE A Introduction to Subtitle A § 1.215... title 2 of the CFR. Specifically: Guidance in * * * On * * * Previously was in * * * (a) Chapter I, part...

  11. 2 CFR 1.215 - Relationship to previous issuances.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 2 Grants and Agreements 1 2012-01-01 2012-01-01 false Relationship to previous issuances. 1.215... ABOUT TITLE 2 OF THE CODE OF FEDERAL REGULATIONS AND SUBTITLE A Introduction to Subtitle A § 1.215... title 2 of the CFR. Specifically: Guidance in * * * On * * * Previously was in * * * (a) Chapter I, part...

  12. 2 CFR 220.40 - Relationship to previous issuance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false Relationship to previous issuance. 220.40 Section 220.40 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements... INSTITUTIONS (OMB CIRCULAR A-21) § 220.40 Relationship to previous issuance. (a) The guidance in this part...

  13. 2 CFR 230.45 - Relationship to previous issuance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false Relationship to previous issuance. 230.45 Section 230.45 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements... ORGANIZATIONS (OMB CIRCULAR A-122) § 230.45 Relationship to previous issuance. (a) The guidance in this part...

  14. 2 CFR 1.215 - Relationship to previous issuances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Relationship to previous issuances. 1.215 Section 1.215 Grants and Agreements ABOUT TITLE 2 OF THE CODE OF FEDERAL REGULATIONS AND SUBTITLE A Introduction toSubtitle A § 1.215 Relationship to previous issuances. Although some of the guidance was...

  15. Metatranscriptomic insights on gene expression and regulatory controls in Candidatus Accumulibacter phosphatis

    DOE PAGES

    Oyserman, Ben O.; Noguera, Daniel R.; del Rio, Tijana Glavina; ...

    2015-11-10

    Previous studies on enhanced biological phosphorus removal (EBPR) have focused on reconstructing genomic blueprints for the model polyphosphate-accumulating organism Candidatus Accumulibacter phosphatis. Here, a time series metatranscriptome generated from enrichment cultures of Accumulibacter was used to gain insight into anerobic/aerobic metabolism and regulatory mechanisms within an EBPR cycle. Co-expressed gene clusters were identified displaying ecologically relevant trends consistent with batch cycle phases. Transcripts displaying increased abundance during anerobic acetate contact were functionally enriched in energy production and conversion, including upregulation of both cytoplasmic and membrane-bound hydrogenases demonstrating the importance of transcriptional regulation to manage energy and electron flux during anerobicmore » acetate contact. We hypothesized and demonstrated hydrogen production after anerobic acetate contact, a previously unknown strategy for Accumulibacter to maintain redox balance. Genes involved in anerobic glycine utilization were identified and phosphorus release after anerobic glycine contact demonstrated, suggesting that Accumulibacter routes diverse carbon sources to acetyl-CoA formation via previously unrecognized pathways. A comparative genomics analysis of sequences upstream of co-expressed genes identified two statistically significant putative regulatory motifs. One palindromic motif was identified upstream of genes involved in PHA synthesis and acetate activation and is hypothesized to be a phaR binding site, hence representing a hypothetical PHA modulon. A second motif was identified ~35 base pairs (bp) upstream of a large and diverse array of genes and hence may represent a sigma factor binding site. As a result, this analysis provides a basis and framework for further investigations into Accumulibacter metabolism and the reconstruction of regulatory networks in uncultured organisms.« less

  16. Metatranscriptomic insights on gene expression and regulatory controls in Candidatus Accumulibacter phosphatis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oyserman, Ben O.; Noguera, Daniel R.; del Rio, Tijana Glavina

    Previous studies on enhanced biological phosphorus removal (EBPR) have focused on reconstructing genomic blueprints for the model polyphosphate-accumulating organism Candidatus Accumulibacter phosphatis. Here, a time series metatranscriptome generated from enrichment cultures of Accumulibacter was used to gain insight into anerobic/aerobic metabolism and regulatory mechanisms within an EBPR cycle. Co-expressed gene clusters were identified displaying ecologically relevant trends consistent with batch cycle phases. Transcripts displaying increased abundance during anerobic acetate contact were functionally enriched in energy production and conversion, including upregulation of both cytoplasmic and membrane-bound hydrogenases demonstrating the importance of transcriptional regulation to manage energy and electron flux during anerobicmore » acetate contact. We hypothesized and demonstrated hydrogen production after anerobic acetate contact, a previously unknown strategy for Accumulibacter to maintain redox balance. Genes involved in anerobic glycine utilization were identified and phosphorus release after anerobic glycine contact demonstrated, suggesting that Accumulibacter routes diverse carbon sources to acetyl-CoA formation via previously unrecognized pathways. A comparative genomics analysis of sequences upstream of co-expressed genes identified two statistically significant putative regulatory motifs. One palindromic motif was identified upstream of genes involved in PHA synthesis and acetate activation and is hypothesized to be a phaR binding site, hence representing a hypothetical PHA modulon. A second motif was identified ~35 base pairs (bp) upstream of a large and diverse array of genes and hence may represent a sigma factor binding site. As a result, this analysis provides a basis and framework for further investigations into Accumulibacter metabolism and the reconstruction of regulatory networks in uncultured organisms.« less

  17. Adult Children of Dysfunctional Families: Treatment from a Disenfranchised Grief Perspective.

    ERIC Educational Resources Information Center

    Zupanick, Corinne E.

    1994-01-01

    Generalizes concept of disenfranchised grief to understanding of recovery process for adult children of dysfunctional families. Describes recovery process of this population as parallel to grief process. Identifies two layers of unrecognized loss: loss of one's childhood and loss of one's fantasized and idealized parent. Suggests specific…

  18. Structured Ethical Reflection in Practitioner Inquiry: Theory, Pedagogy, and Practice

    ERIC Educational Resources Information Center

    Stevens, Douglas M.; Brydon-Miller, Mary; Raider-Roth, Miriam

    2016-01-01

    Practitioner inquiry provides a powerful tool for improving practice and addressing critical issues in classrooms, schools, and broader communities. However, it also raises unique ethical challenges that often go unrecognized and unresolved. Structured Ethical Reflection (SER) provides teacher researchers with a process for identifying core values…

  19. 2 CFR 1.215 - Relationship to previous issuances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false Relationship to previous issuances. 1.215... ABOUT TITLE 2 OF THE CODE OF FEDERAL REGULATIONS AND SUBTITLE A Introduction toSubtitle A § 1.215... title 2 of the CFR. Specifically: Guidance in * * * On * * * Previously was in * * * (a) Chapter I, part...

  20. 44 CFR 402.5 - Forwarding commodities previously shipped.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Forwarding commodities previously shipped. 402.5 Section 402.5 Emergency Management and Assistance DEPARTMENT OF COMMERCE AND DEPARTMENT OF TRANSPORTATION SHIPMENTS ON AMERICAN FLAG SHIPS AND AIRCRAFT (T-1, INT. 1) § 402.5 Forwarding commodities previously shipped. Order T-1...

  1. Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer.

    PubMed

    Beaugerie, Laurent; Carrat, Fabrice; Colombel, Jean-Frédéric; Bouvier, Anne-Marie; Sokol, Harry; Babouri, Abdenour; Carbonnel, Franck; Laharie, David; Faucheron, Jean-Luc; Simon, Tabassome; de Gramont, Aimery; Peyrin-Biroulet, Laurent

    2014-09-01

    To explore the risk of new or recurrent cancer among patients with IBD and previous cancer, exposed or not to immunosuppressants. Among the 17 047 patients of the CESAME prospective observational cohort who were enrolled from May 2004 to June 2005, and followed-up until December 2007, we identified 405 patients with cancer diagnosed previous to study entry. We calculated the rates of incident cancer in patients with or without previous cancer, and we assessed by survival analysis and nested case-control study the impact of immunosuppressants on the risk of incident new or recurrent cancer in patients with previous cancer. The rate of incident cancer was 21.1/1000 patient-years (PY) and 6.1/1000 PY in patients with and without previous cancer, respectively. The multivariate-adjusted HR of incident cancer between patients with and without previous cancer was 1.9 (95% CI 1.2 to 3.0, p=0.003). Among patients with previous cancer, the rates of new and recurrent cancers were, respectively, 13.2/1000 PY and 6.0/1000 PY in the 312 patients who were not taking immunosuppressant at the time of study entry, and 23.1/1000 PY and 3.9/1000 PY in the 93 patients treated with immunosuppressants at study entry. There was no significant association between the exposure to immunosuppressants and the risk of new or recurrent cancer. Patients with IBD with a history of cancer are at increased risk of developing any (new or recurrent) cancer, with a predominant incidence of new cancers. Treatment with immunosuppressants has no overall major impact per se on this risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Sleep Disordered Breathing in Heart Failure: Identifying and Treating an Important but Often Unrecognized Comorbidity in Heart Failure Patients

    PubMed Central

    Khayat, Rami; Small, Roy; Rathman, Lisa; Krueger, Steven; Gocke, Becky; Clark, Linda; Yamokoski, Laura; Abraham, William T.

    2013-01-01

    Sleep disordered breathing (SDB) is the most common co-morbidity in patients with heart failure (HF) and has a significant impact on quality of life, morbidity, and mortality. A number of therapeutic options have become available in recent years that can improve quality of life and potentially the outcomes of HF patients with SDB. Unfortunately, SDB is not part of the routine evaluation and management of HF, thus it remains untreated in most HF patients. While recognition of the role of SDB in HF is increasing, clinical guidelines for the management of SDB in HF patients continue to be absent. In this article we provide an overview of SDB in HF and propose a clinical care pathway to help clinicians better recognize and treat SDB in their HF patients. PMID:23743494

  3. Active faults newly identified in Pacific Northwest

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2012-05-01

    The Bellingham Basin, which lies north of Seattle and south of Vancouver around the border between the United States and Canada in the northern part of the Cascadia subduction zone, is important for understanding the regional tectonic setting and current high rates of crustal deformation in the Pacific Northwest. Using a variety of new data, Kelsey et al. identified several active faults in the Bellingham Basin that had not been previously known. These faults lie more than 60 kilometers farther north of the previously recognized northern limit of active faulting in the area. The authors note that the newly recognized faults could produce earthquakes with magnitudes between 6 and 6.5 and thus should be considered in hazard assessments for the region. (Journal of Geophysical Reserch-Solid Earth, doi:10.1029/2011JB008816, 2012)

  4. Previous pregnancy outcomes and subsequent pregnancy anxiety in a Quebec prospective cohort

    PubMed Central

    Shapiro, Gabriel D.; Séguin, Jean R.; Muckle, Gina; Monnier, Patricia; Fraser, William D.

    2017-01-01

    Introduction Pregnancy anxiety is an important psychosocial risk factor that may be more strongly associated with adverse birth outcomes than other measures of stress. Better understanding of the upstream predictors and causes of pregnancy anxiety could help to identify high-risk women for adverse maternal and infant outcomes. The objective of the present study was to measure the associations between five past pregnancy outcomes (live preterm birth (PTB), live term birth, miscarriage at <20 weeks, stillbirth at ≥20 weeks, and elective abortion) and pregnancy anxiety at three trimesters in a subsequent pregnancy. Methods Analyses were conducted using data from the 3D Cohort Study, a Canadian birth cohort. Data on maternal demographic characteristics and pregnancy history for each known previous pregnancy were collected via interviewer-administered questionnaires at study entry. Pregnancy anxiety for the index study pregnancy was measured prospectively by self-administered questionnaire following three prenatal study visits. Results Of 2366 participants in the 3D Study, 1505 had at least one previous pregnancy. In linear regression analyses with adjustment for confounding variables, prior live term birth was associated with lower pregnancy anxiety in all three trimesters, whereas prior miscarriage was significantly associated with higher pregnancy anxiety in the first trimester. Prior stillbirth was associated with greater pregnancy anxiety in the third trimester. Prior elective abortion was significantly associated with higher pregnancy anxiety scores in the first and second trimesters, with an association of similar magnitude observed in the third trimester. Discussion Our findings suggest that the outcomes of previous pregnancies should be incorporated, along with demographic and psychosocial characteristics, into conceptual models framing pregnancy anxiety. PMID:28079434

  5. Characteristics of an outbreak of West Nile virus encephalomyelitis in a previously uninfected population of horses.

    PubMed

    Ward, Michael P; Schuermann, James A; Highfield, Linda D; Murray, Kristy O

    2006-12-20

    Equine West Nile virus (WNV) encephalomyelitis cases - based on clinical signs and ELISA serology test results - reported to Texas disease control authorities during 2002 were analyzed to provide insights into the epidemiology of the disease within a previously disease-free population. The epidemic occurred between June 27 and December 17 (peaking in early October) and 1,698 cases were reported. Three distinct epidemic phases were identified, occurring mostly in southeast, northwest and then central Texas. Significant (P<0.05) disease clusters were identified in northwest and northern Texas. Most (91.1%) cases had no recent travel history, and most (68.9%) cases had not been vaccinated within the previous 12 months. One-third of cases did not survive, 71.2% of which were euthanatized. The most commonly reported presenting signs included ataxia (69%), abnormal gait (52%), muscle fasciculations (49%), depression (32%) and recumbency (28%). Vaccination status, ataxia, falling down, recumbency and lip droop best explained the risk of not surviving WNV disease. Results suggest that the peak risk period for encephalomyelitis caused by WNV may vary substantially among regions within Texas. Recumbent horses have a poor prognosis for survival. Vaccines, even if not administered sufficiently in advance of WNV infection within a district, may reduce the risk of death by at least 44%.

  6. School Disconnectedness: Identifying Adolescents at Risk in Ontario, Canada

    ERIC Educational Resources Information Center

    Faulkner, Guy E. J.; Adlaf, Edward M.; Irving, Hyacinth M.; Allison, Kenneth R.; Dwyer, John

    2009-01-01

    Background: There is strong theoretical and empirical support for school connectedness as an important element of healthy youth development. The primary objective of this study was to replicate previous research identifying factors differentiating youth who do not feel connected to their schools in a sample of adolescents in Ontario, Canada. A…

  7. Using cluster ensemble and validation to identify subtypes of pervasive developmental disorders.

    PubMed

    Shen, Jess J; Lee, Phil-Hyoun; Holden, Jeanette J A; Shatkay, Hagit

    2007-10-11

    Pervasive Developmental Disorders (PDD) are neurodevelopmental disorders characterized by impairments in social interaction, communication and behavior. Given the diversity and varying severity of PDD, diagnostic tools attempt to identify homogeneous subtypes within PDD. Identifying subtypes can lead to targeted etiology studies and to effective type-specific intervention. Cluster analysis can suggest coherent subsets in data; however, different methods and assumptions lead to different results. Several previous studies applied clustering to PDD data, varying in number and characteristics of the produced subtypes. Most studies used a relatively small dataset (fewer than 150 subjects), and all applied only a single clustering method. Here we study a relatively large dataset (358 PDD patients), using an ensemble of three clustering methods. The results are evaluated using several validation methods, and consolidated through an integration step. Four clusters are identified, analyzed and compared to subtypes previously defined by the widely used diagnostic tool DSM-IV.

  8. Newly identified allatostatin Bs and their receptor in the two-spotted cricket, Gryllus bimaculatus.

    PubMed

    Tsukamoto, Yusuke; Nagata, Shinji

    2016-06-01

    A cDNA encoding allatostatin Bs (ASTBs) containing the W(X)6W motif was identified using a database generated by a next generation sequencer (NGS) in the two-spotted cricket, Gryllus bimaculatus. The contig sequence revealed the presence of five novel putative ASTBs (GbASTBs) in addition to GbASTBs previously identified in G. bimaculatus. MALDI-TOF MS analyses revealed the presence of these novel and previously identified GbASTBs with three missing GbASTBs. We also identified a cDNA encoding G. bimaculatus GbASTB receptor (GbASTBR) in the NGS data. Phylogenetic analysis demonstrated that this receptor was highly conserved with other insect ASTBRs, including the sex peptide receptor of Drosophila melanogaster. Calcium imaging analyses indicated that the GbASTBR heterologously expressed in HEK293 cells exhibited responses to all identified GbASTBs at a concentration range of 10(-10)-10(-5)M. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

    PubMed Central

    Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

    2013-01-01

    Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value < 1.0 × 10-4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value < 5.0 × 10-8); three found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

  10. 78 FR 41888 - Airworthiness Directives; AgustaWestland S.p.A. (Type Certificate Previously Held by Agusta S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ...-0604; Directorate Identifier 2012-SW-110-AD] RIN 2120-AA64 Airworthiness Directives; AgustaWestland S.p.A. (Type Certificate Previously Held by Agusta S.p.A.) Helicopters AGENCY: Federal Aviation... (AD): AgustaWestland S.p.A. (Type Certificate Formerly Held By Agusta S.p.A.) Helicopters: Docket No...

  11. Wall teichoic acids prevent antibody binding to epitopes within the cell wall of Staphylococcus aureus.

    PubMed

    Gautam, Samir; Kim, Taehan; Lester, Evan; Deep, Deeksha; Spiegel, David A

    2016-01-15

    Staphylococcus aureus is a Gram-positive bacterial pathogen that produces a range of infections including cellulitis, pneumonia, and septicemia. The principle mechanism in antistaphylococcal host defense is opsonization with antibodies and complement proteins, followed by phagocytic clearance. Here we use a previously developed technique for installing chemical epitopes in the peptidoglycan cell wall to show that surface glycopolymers known as wall teichoic acids conceal cell wall epitopes, preventing their recognition and opsonization by antibodies. Thus, our results reveal a previously unrecognized immunoevasive role for wall teichoic acids in S. aureus: repulsion of peptidoglycan-targeted antibodies.

  12. Unsuspected glucose-6-phosphate dehydrogenase deficiency presenting as symptomatic methemoglobinemia with severe hemolysis after fava bean ingestion in a 6-year-old boy.

    PubMed

    Odièvre, Marie-Hélène; Danékova, Névéna; Mesples, Bettina; Chemouny, Myriam; Couque, Nathalie; Parez, Nathalie; Ducrocq, Rolande; Elion, Jacques

    2011-05-01

    We report the occurrence of symptomatic methemoglobinemia in a previously healthy boy, who presented with severe acute hemolysis after fava bean ingestion. The methemoglobinemia revealed a previously unrecognized glucose-6-phosphate dehydrogenase (G6PD) deficiency. We discuss the pathophysiology of severe methemoglobinemia when associated with acute hemolysis, favism, and the common African G6PD A-variant [G6PD, VAL68MET, ASN126ASP]. In conclusion, screening for G6PD deficiency must be considered in symptomatic methemoglobinemia, especially in young boys, when associated with intravascular hemolysis.

  13. Influence of an Identified Advisor/Mentor on Urban Latino Students' College Experience

    ERIC Educational Resources Information Center

    Torres, Vasti; Hernandez, Ebelia

    2010-01-01

    This study considers the scales previously used by Nora, Kraemer, and Itzen (1997) and Torres (2006) as contributing to the retention of Latino/a college students. T-tests were used to compare the scale means between students with an identified advisor or mentor and those that have not identified one. The data is from Latino college students at…

  14. Rainfall-enhanced blooming in typhoon wakes

    PubMed Central

    Lin, Y.-C.; Oey, L.-Y.

    2016-01-01

    Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm. PMID:27545899

  15. Deciphering functional diversification within the lichen microbiota by meta-omics.

    PubMed

    Cernava, Tomislav; Erlacher, Armin; Aschenbrenner, Ines Aline; Krug, Lisa; Lassek, Christian; Riedel, Katharina; Grube, Martin; Berg, Gabriele

    2017-07-19

    Recent evidence of specific bacterial communities extended the traditional concept of fungal-algal lichen symbioses by a further organismal kingdom. Although functional roles were already assigned to dominant members of the highly diversified microbiota, a substantial fraction of the ubiquitous colonizers remained unexplored. We employed a multi-omics approach to further characterize functional guilds in an unconventional model system. The general community structure of the lichen-associated microbiota was shown to be highly similar irrespective of the employed omics approach. Five highly abundant bacterial orders-Sphingomonadales, Rhodospirillales, Myxococcales, Chthoniobacterales, and Sphingobacteriales-harbor functions that are of substantial importance for the holobiome. Identified functions range from the provision of vitamins and cofactors to the degradation of phenolic compounds like phenylpropanoid, xylenols, and cresols. Functions that facilitate the persistence of Lobaria pulmonaria under unfavorable conditions were present in previously overlooked fractions of the microbiota. So far, unrecognized groups like Chthoniobacterales (Verrucomicrobia) emerged as functional protectors in the lichen microbiome. By combining multi-omics and imaging techniques, we highlight previously overlooked participants in the complex microenvironment of the lichens.

  16. Synthesis of instrumentally and historically recorded earthquakes and studying their spatial statistical relationship (A case study: Dasht-e-Biaz, Eastern Iran)

    NASA Astrophysics Data System (ADS)

    Jalali, Mohammad; Ramazi, Hamidreza

    2018-06-01

    Earthquake catalogues are the main source of statistical seismology for the long term studies of earthquake occurrence. Therefore, studying the spatiotemporal problems is important to reduce the related uncertainties in statistical seismology studies. A statistical tool, time normalization method, has been determined to revise time-frequency relationship in one of the most active regions of Asia, Eastern Iran and West of Afghanistan, (a and b were calculated around 8.84 and 1.99 in the exponential scale, not logarithmic scale). Geostatistical simulation method has been further utilized to reduce the uncertainties in the spatial domain. A geostatistical simulation produces a representative, synthetic catalogue with 5361 events to reduce spatial uncertainties. The synthetic database is classified using a Geographical Information System, GIS, based on simulated magnitudes to reveal the underlying seismicity patterns. Although some regions with highly seismicity correspond to known faults, significantly, as far as seismic patterns are concerned, the new method highlights possible locations of interest that have not been previously identified. It also reveals some previously unrecognized lineation and clusters in likely future strain release.

  17. Rainfall-enhanced blooming in typhoon wakes.

    PubMed

    Lin, Y-C; Oey, L-Y

    2016-08-22

    Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm.

  18. Rainfall-enhanced blooming in typhoon wakes

    NASA Astrophysics Data System (ADS)

    Lin, Y.-C.; Oey, L.-Y.

    2016-08-01

    Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm.

  19. Rainfall-enhanced blooming in typhoon wakes

    NASA Astrophysics Data System (ADS)

    Lin, Y.; Oey, L. Y.

    2016-12-01

    Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm.

  20. Need for new sensors to map lithologic units

    USGS Publications Warehouse

    Rowan, Lawrence C.; Barringer, Anthony R.

    1980-01-01

    One of the most important contributions that remote sensing can make to mineral energy explorations to provide data from satellites to augment regional geological mapping. Geologic maps, which show information on the subsurface, are the main basis for formulating models of resource genesis that guide exploration. However, conventional compilation procedures are time-consuming and therefore often slow the pace of exploration, especially in large, inaccessible areas. Landsat Multispectral Scanner (MSS) images have been applied to a wide variety of specific geological problems, including discrimination of lithologic and delineation of previously unrecognized tectonic features. However, these lithologic distinctions are based on brightness, spectral reflectance, and, less commonly, the morphology of the unit, which in the wavelength region of MSS images are only rarely diagnostic of specific mineralogical content. Limonite is the only lithological material that can be identified be analyzing MSS spectral radiance.

  1. Volcanic Structures Within Niger and Dao Valles, Mars, and Implications for Outflow Channel Evolution and Hellas Basin Rim Development

    NASA Astrophysics Data System (ADS)

    Korteniemi, J.; Kukkonen, S.

    2018-04-01

    Outflow channel formation on the eastern Hellas rim region is traditionally thought to have been triggered by activity phases of the nearby volcanoes Hadriacus and Tyrrhenus Montes: As a result of volcanic heating subsurface volatiles were mobilized. It is, however, under debate, whether eastern Hellas volcanism was in fact more extensive, and if there were volcanic centers separate from the identified central volcanoes. This work describes previously unrecognized structures in the Niger-Dao Valles outflow channel complex. We interpret them as volcanic edifices: cones, a shield, and a caldera. The structures provide evidence of an additional volcanic center within the valles and indicate volcanic activity both prior to and following the formation of the outflow events. They expand the extent, type, and duration of volcanic activity in the Circum-Hellas Volcanic Province and provide new information on interaction between volcanism and fluvial activity.

  2. Marine environment pollution: The contribution of mass spectrometry to the study of seawater.

    PubMed

    Magi, Emanuele; Di Carro, Marina

    2016-09-09

    The study of marine pollution has been traditionally addressed to persistent chemicals, generally known as priority pollutants; a current trend in environmental analysis is a shift toward "emerging pollutants," defined as newly identified or previously unrecognized contaminants. The present review is focused on the peculiar contribution of mass spectrometry (MS) to the study of pollutants in the seawater compartment. The work is organized in five paragraphs where the most relevant groups of pollutants, both "classical" and "emerging," are presented and discussed, highlighting the relative data obtained by the means of different MS techniques. The hyphenation of MS and separative techniques, together with the development of different ion sources, makes MS and tandem MS the analytical tool of choice for the determination of trace organic contaminants in seawater. © 2016 Wiley Periodicals, Inc. Mass Spec Rev. © 2016 Wiley Periodicals, Inc.

  3. Identifying a gene expression signature of cluster headache in blood

    PubMed Central

    Eising, Else; Pelzer, Nadine; Vijfhuizen, Lisanne S.; Vries, Boukje de; Ferrari, Michel D.; ‘t Hoen, Peter A. C.; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.

    2017-01-01

    Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headache. PMID:28074859

  4. Hypertension among Oral Contraceptive Users in El Paso, Texas

    PubMed Central

    White, Kari; Potter, Joseph E.; Hopkins, Kristine; Amastae, Jon; Grossman, Daniel

    2015-01-01

    On the U.S.-Mexico border, residents frequently cross into Mexico to obtain medications or medical care. We previously reported relatively high prevalence of hypertension among Latina oral contraceptive users in El Paso, particularly those obtaining pills over the counter (OTC) in Mexico. Here, we examine factors associated with having hypertension among 411 OTC users and 399 clinic users. We also assess hypertension awareness and interest in using blood pressure kiosks. Women age 35 to 44 and who had BMI ≥ 30 kg/m2 had higher odds of having hypertension. 59% of hypertensive women had unrecognized hypertension, and 77% of all participants would use a blood pressure kiosk; there were no significant differences between clinic and OTC users. Alternative approaches to increase access to health screenings are needed in this setting, where OTC pill use among women with unrecognized hypertension confers unique health risks. PMID:24185148

  5. Metabonomics identifies serum metabolite markers of colorectal cancer.

    PubMed

    Tan, Binbin; Qiu, Yunping; Zou, Xia; Chen, Tianlu; Xie, Guoxiang; Cheng, Yu; Dong, Taotao; Zhao, Linjing; Feng, Bo; Hu, Xiaofang; Xu, Lisa X; Zhao, Aihua; Zhang, Menghui; Cai, Guoxiang; Cai, Sanjun; Zhou, Zhanxiang; Zheng, Minhua; Zhang, Yan; Jia, Wei

    2013-06-07

    Recent studies suggest that biofluid-based metabonomics may identify metabolite markers promising for colorectal cancer (CRC) diagnosis. We report here a follow-up replication study, after a previous CRC metabonomics study, aiming to identify a distinct serum metabolic signature of CRC with diagnostic potential. Serum metabolites from newly diagnosed CRC patients (N = 101) and healthy subjects (N = 102) were profiled using gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). Differential metabolites were identified with statistical tests of orthogonal partial least-squares-discriminant analysis (VIP > 1) and the Mann-Whitney U test (p < 0.05). With a total of 249 annotated serum metabolites, we were able to differentiate CRC patients from the healthy controls using an orthogonal partial least-squares-discriminant analysis (OPLS-DA) in a learning sample set of 62 CRC patients and 62 matched healthy controls. This established model was able to correctly assign the rest of the samples to the CRC or control groups in a validation set of 39 CRC patients and 40 healthy controls. Consistent with our findings from the previous study, we observed a distinct metabolic signature in CRC patients including tricarboxylic acid (TCA) cycle, urea cycle, glutamine, fatty acids, and gut flora metabolism. Our results demonstrated that a panel of serum metabolite markers is of great potential as a noninvasive diagnostic method for the detection of CRC.

  6. Criterion for Identifying Vortices in High-Pressure Flows

    NASA Technical Reports Server (NTRS)

    Bellan, Josette; Okong'o, Nora

    2007-01-01

    A study of four previously published computational criteria for identifying vortices in high-pressure flows has led to the selection of one of them as the best. This development can be expected to contribute to understanding of high-pressure flows, which occur in diverse settings, including diesel, gas turbine, and rocket engines and the atmospheres of Jupiter and other large gaseous planets. Information on the atmospheres of gaseous planets consists mainly of visual and thermal images of the flows over the planets. Also, validation of recently proposed computational models of high-pressure flows entails comparison with measurements, which are mainly of visual nature. Heretofore, the interpretation of images of high-pressure flows to identify vortices has been based on experience with low-pressure flows. However, high-pressure flows have features distinct from those of low-pressure flows, particularly in regions of high pressure gradient magnitude caused by dynamic turbulent effects and by thermodynamic mixing of chemical species. Therefore, interpretations based on low-pressure behavior may lead to misidentification of vortices and other flow structures in high-pressure flows. The study reported here was performed in recognition of the need for one or more quantitative criteria for identifying coherent flow structures - especially vortices - from previously generated flow-field data, to complement or supersede the determination of flow structures by visual inspection of instantaneous fields or flow animations. The focus in the study was on correlating visible images of flow features with various quantities computed from flow-field data.

  7. Distractor Repetitions Retrieve Previous Responses and Previous Targets: Experimental Dissociations of Distractor-Response and Distractor-Target Bindings

    ERIC Educational Resources Information Center

    Giesen, Carina; Rothermund, Klaus

    2014-01-01

    Even an irrelevant distractor stimulus is integrated into event files. Subsequently repeating the distractor triggers retrieval of the event file; however, an unresolved issue concerns the question of "what" is retrieved by the distractor. While recent studies predominantly assume that the distractor retrieves the previous response, it…

  8. 26 CFR 1.860A-0 - Outline of REMIC provisions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... foreign persons. § 1.860C-2Determination of REMIC taxable income or net loss. (a) Treatment of gain or... gain or loss. (3) Basis of contributed assets allocated among interests. (i) In general. (ii...) Treatment of unrecognized gain or loss. (i) Unrecognized gain on regular interests. (ii) Unrecognized loss...

  9. 26 CFR 1.1092(b)-5T - Definitions (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

  10. 26 CFR 1.1092(b)-5T - Definitions (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

  11. 26 CFR 1.1092(b)-5T - Definitions (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

  12. 26 CFR 1.1092(b)-5T - Definitions (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

  13. 26 CFR 1.1092(b)-5T - Definitions (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... defined in sections 1092(d)(4) (B) and (C) respectively. (k) Section 1256 contract. The term section 1256... referred to in paragraph (n)(1) of this section. (o) Unrecognized gain. The term unrecognized gain means unrecognized gain as defined in section 1092(a)(3)(A). (p) Substantially identical. The term substantially...

  14. Epidemic of complicated mumps in previously vaccinated young adults in the South-West of France.

    PubMed

    Vareil, M-O; Rouibi, G; Kassab, S; Soula, V; Duffau, P; Lafon, M-E; Neau, D; Cazanave, C

    2014-12-01

    We report the features and diagnosis of complicated mumps in previously vaccinated young adults. We retrospectively studied 7 cases of complicated mumps managed during 1 year at the Bordeaux University Hospital. The diagnosis was suggested by the clinical presentation and confirmed using specific RT-PCR. Five cases of meningitis, 1 of orchitis, and 1 of unilateral hearing impairment were identified. Each of the 7 patients had been previously vaccinated with MMR, 4 had received 2 doses of this vaccine. Blood tests revealed high rates of IgG antibodies, usually considered as sufficient for immunological protection, and every patient had at least 1 positive RT-PCR test for mumps. Outbreaks of complicated mumps may still occur despite a broad coverage of MMR vaccination. The clinical presentation suggested mumps but the final diagnosis could only be confirmed by genomic detection of the virus. Unusual viral strains with increased neurovirulence, insufficient population coverage associated with immunity decrease over time may explain outbreaks of complicated mumps. A full vaccine scheme of contact people or a third injection of vaccine for previously vaccinated people who are at risk of developing mumps are required to prevent further spreading of the disease during the outbreak. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Structural Identifiability of Dynamic Systems Biology Models

    PubMed Central

    Villaverde, Alejandro F.

    2016-01-01

    A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areas. PMID:27792726

  16. Left Axis Deviation in Children Without Previously Known Heart Disease.

    PubMed

    Schneider, Andrew E; Cannon, Bryan C; Johnson, Jonathan N; Ackerman, Michael J; Wackel, Philip L

    2018-02-01

    Left axis deviation (LAD) discovered in children via electrocardiogram (ECG) is uncommon but can be associated with heart disease (HD). The optimal diagnostic approach in a seemingly healthy child with LAD is unclear. We sought to better stratify which patients with LAD but without previously known HD may warrant additional workup. A retrospective chart review was performed to identify patients ≥1 to <18 years of age with LAD (QRS frontal plane axis 0 to -90) on an ECG between January 2002 and December 2014. Patients with known HD before their initial ECG were excluded. Overall, 296 patients were identified ( n = 181 [61%] male; mean age: 10.8 ± 4.6 years; mean QRS axis: -24 ± 22°). An echocardiogram was performed in 158 (53%) patients, with 24 (15%) having HD. Compared with those with an echocardiogram but without HD ( n = 134), patients with HD had a more negative mean QRS axis (-42 vs -27°; P = .002) and were more likely to have a QRS axis ≤-42° (58% vs 26%; P = .003), ECG chamber enlargement or hypertrophy (38% vs 5%; P < .0001), and abnormal cardiac physical examination findings (75% vs 8%; P < .0001). LAD discovered in isolation in the asymptomatic pediatric patient may not necessitate further cardiovascular investigation. Clinicians should consider obtaining an echocardiogram in patients with LAD and ECG cardiac chamber enlargement or hypertrophy, a QRS axis ≤-42°, and/or the presence of abnormal cardiac physical examination findings. Copyright © 2018 by the American Academy of Pediatrics.

  17. [Prevalence of previously diagnosed diabetes mellitus in Mexico.

    PubMed

    Rojas-Martínez, Rosalba; Basto-Abreu, Ana; Aguilar-Salinas, Carlos A; Zárate-Rojas, Emiliano; Villalpando, Salvador; Barrientos-Gutiérrez, Tonatiuh

    2018-01-01

    To compare the prevalence of previously diagnosed diabetes in 2016 with previous national surveys and to describe treatment and its complications. Mexico's national surveys Ensa 2000, Ensanut 2006, 2012 and 2016 were used. For 2016, logistic regression models and measures of central tendency and dispersion were obtained. The prevalence of previously diagnosed diabetes in 2016 was 9.4%. The increase of 2.2% relative to 2012 was not significant and only observed in patients older than 60 years. While preventive measures have increased, the access to medical treatment and lifestyle has not changed. The treatment has been modified, with an increase in insulin and decrease in hypoglycaemic agents. Population aging, lack of screening actions and the increase in diabetes complications will lead to an increase on the burden of disease. Policy measures targeting primary and secondary prevention of diabetes are crucial.

  18. Strategies and Challenges in Identifying Function for Thousands of sORF-Encoded Peptides in Meiosis.

    PubMed

    Hollerer, Ina; Higdon, Andrea; Brar, Gloria A

    2017-09-20

    Recent genomic analyses have revealed pervasive translation from formerly unrecognized short open reading frames (sORFs) during yeast meiosis. Despite their short length, which has caused these regions to be systematically overlooked by traditional gene annotation approaches, meiotic sORFs share many features with classical genes, implying the potential for similar types of cellular functions. We found that sORF expression accounts for approximately 10-20% of the cellular translation capacity in yeast during meiotic differentiation and occurs within well-defined time windows, suggesting the production of relatively abundant peptides with stage-specific meiotic roles from these regions. Here, we provide arguments supporting this hypothesis and discuss sORF similarities and differences, as a group, to traditional protein coding regions, as well as challenges in defining their specific functions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Cardioprotective medication use and risk factor control among US adults with unrecognized myocardial infarction: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study

    PubMed Central

    Levitan, Emily B; Gamboa, Christopher; Safford, Monika M; Rizk, Dana V; Brown, Todd M; Soliman, Elsayed Z; Muntner, Paul

    2013-01-01

    Background Individuals with unrecognized myocardial infarction (UMI) have similar risks for cardiovascular events and mortality as those with recognized myocardial infarction (RMI). The prevalence of cardioprotective medication use and blood pressure and low-density lipoprotein cholesterol control among individuals with UMI is unknown. Methods Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were recruited between May 2004 and October 2007 received baseline twelve-lead electrocardiograms (n = 21,036). Myocardial infarction (MI) status was characterized as no MI, UMI (electrocardiogram abnormalities consistent with MI without self-reported history; n = 949; 4.5%), and RMI (self-reported history of MI; n = 1574; 7.5%). Results For participants with no MI, UMI, and RMI, prevalence of use was 38.4%, 44.4%, and 75.7% for aspirin; 18.0%, 25.8%, and 57.2% for beta blockers; 31.7%, 38.7%, and 55.0% for angiotensin converting enzyme inhibitors or angiotensin receptor blockers; and 28.1%, 33.9%, and 64.1% for statins, respectively. Participants with RMI were 35% more likely to have low-density lipoprotein cholesterol < 100 mg/dL than participants with UMI (prevalence ratio = 1.35, 95% confidence interval 1.19–1.52). Blood pressure control (,140/90 mmHg) was similar between RMI and UMI groups (prevalence ratio = 1.03, 95% confidence interval 0.93–1.13). Conclusion Although participants with UMI were somewhat more likely to use cardioprotective medications than those with no MI, they were less likely to use cardioprotective medications and to have controlled low-density lipoprotein cholesterol than participants with RMI. Increasing appropriate treatment and risk factor control among individuals with UMI may reduce risk of mortality and future cardiovascular events. PMID:23404361

  20. Using Cluster Ensemble and Validation to Identify Subtypes of Pervasive Developmental Disorders

    PubMed Central

    Shen, Jess J.; Lee, Phil Hyoun; Holden, Jeanette J.A.; Shatkay, Hagit

    2007-01-01

    Pervasive Developmental Disorders (PDD) are neurodevelopmental disorders characterized by impairments in social interaction, communication and behavior.1 Given the diversity and varying severity of PDD, diagnostic tools attempt to identify homogeneous subtypes within PDD. Identifying subtypes can lead to targeted etiology studies and to effective type-specific intervention. Cluster analysis can suggest coherent subsets in data; however, different methods and assumptions lead to different results. Several previous studies applied clustering to PDD data, varying in number and characteristics of the produced subtypes19. Most studies used a relatively small dataset (fewer than 150 subjects), and all applied only a single clustering method. Here we study a relatively large dataset (358 PDD patients), using an ensemble of three clustering methods. The results are evaluated using several validation methods, and consolidated through an integration step. Four clusters are identified, analyzed and compared to subtypes previously defined by the widely used diagnostic tool DSM-IV.2 PMID:18693920

  1. A new worm infiltrating the human cornea: A report of three cases.

    PubMed

    McBurney-Lin, Shan; Khorram, David; Gee, Stephen; Hoberg, Eric P; Klassen-Fischer, Mary K; Neafie, Ronald C

    2018-03-01

    To characterize a new species of parasitic nematode that triggers uveitis. Three previously healthy, relatively young people each contracted a corneal stromal nematode that, upon surgical removal and examination, did not match any known nematodes. Clinical ocular findings included corneal opacification, visible corneal worms, conjunctival injection, and uveitis. The three cases presented here represent a previously undescribed parasitic infection of the cornea by an unidentified nematode. These findings may represent a previously unrecognized zoonotic infection from wildlife sources and potentially a newly documented nematode requiring description. Future clinical findings regarding this newly described nematode are needed to further develop our understanding of the disease.

  2. Early detection of hospitalized patients with previously diagnosed obstructive sleep apnea using computer decision support alerts.

    PubMed

    Evans, R Scott; Flint, Vrena B; Cloward, Tom V; Beninati, William; Lloyd, James F; Megwalu, Kimberly; Simpson, Kathy J; Alsharit, Ahmed M; Balls, Shayna B; Farney, Robert J

    2013-01-01

    Obstructive sleep apnea (OSA) is a worldwide problem affecting 2-14% of the general population and most patients remain undiagnosed. OSA patients are at elevated risk for hypoxemia, cardiac arrhythmias, cardiorespiratory arrest, hypoxic encephalopathy, stroke and death during hospitalization. Clinical screening questionnaires are used to identify hospitalized patients with OSA; especially before surgery. However, current screening questionnaires miss a significant number of patients and require more definitive testing before specific therapy can be started. Moreover, many patients are admitted to the hospital with a previous diagnosis of OSA that is not reported. Thus, many patients with OSA do not receive appropriate therapy during hospitalization due to the lack of information from previous inpatient and outpatient encounters. Large enterprise data warehouses provide the ability to monitor patient encounters over wide geographical areas. This study found that previously diagnosed OSA is highly prevalent and undertreated in hospitalized patients and the use of early computer alerts by respiratory therapists resulted in significantly more OSA patients receiving appropriate medical care (P < 0.002) which resulted in significantly fewer experiencing hypoxemia (P < 0.006). The impact was greater for non-surgery patients compared to surgery patients.

  3. Identifying the Educationally Influential Physician: A Systematic Review of Approaches

    ERIC Educational Resources Information Center

    Kronberger, Matthew P.; Bakken, Lori L.

    2011-01-01

    Introduction: Previous studies have indicated that educationally influential physicians' (EIPs) interactions with peers can lead to practice changes and improved patient outcomes. However, multiple approaches have been used to identify and investigate EIPs' informal or formal influence on practice, which creates study outcomes that are difficult…

  4. Active case finding for carbapenemase-producing Enterobacteriaceae in a teaching hospital: prevalence and risk factors for colonization.

    PubMed

    Poole, K; George, R; Decraene, V; Shankar, K; Cawthorne, J; Savage, N; Welfare, W; Dodgson, A

    2016-10-01

    Over the past decade, the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) has increased. Whilst basic infection prevention and control practices reduce the risk of transmission, cases of unrecognized carriage pose a potential risk of transmission. To estimate the prevalence of CPE and explore risk factors associated with colonization within a large teaching hospital with an established CPE outbreak. All inpatients that had not previously tested positive for CPE were offered testing. Demographic and hospital episode data were also collected, together with antibiotic and proton pump inhibitor (PPI) use in the preceding 24h. This study identified 70 CPE-positive cases (26 newly identified and 44 previously known) and 592 CPE-negative cases, giving a combined prevalence of 11% [95% confidence interval (CI) 8-13]. Medication (antibiotic and PPI use), previous admission, ethnicity and length of stay were assessed as risk factors for colonization, and none were found to be independently associated with CPE colonization. Using logistic regression, age [odds ratio (OR) 1.03, 95% CI 1.01-1.07] and antibiotic use (OR 2.55, 95% CI 1.08-6.03) were the only risk factors significantly associated with CPE colonization. This study has added to the evidence base by estimating the prevalence of CPE among inpatients in an acute hospital with an established CPE outbreak. A case-finding exercise was feasible and identified a number of new cases. Despite a small sample size, increasing age and prescription of an antibiotic on the day of testing were significantly associated with CPE colonization. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  5. Oculocutaneous albinism: identifying and overcoming barriers to vision care in a Nigerian population.

    PubMed

    Udeh, N N; Eze, B I; Onwubiko, S N; Arinze, O C; Onwasigwe, E N; Umeh, R E

    2014-06-01

    To assess eye care service utilization, and identify access barriers in a south-eastern Nigerian albino population. The study was a population-based, cross-sectional survey conducted in Enugu state between August, 2011 and January, 2012. Using the data base of the state's Albino Foundation and tailored awareness creation, persons living with albinism were identified and recruited at two study centres. Data on participants' socio-demographics, perception of vision, visual needs, previous eye examination and or low vision assessment, use of glasses or low vision devices were collected. Reasons for non-utilisation of available vision care services were also obtained. Descriptive and comparative statistics were performed. A p < 0.05 was considered statistically significant. The participants (n = 153; males 70; females 83; sex ratio: 1:1.1) were aged 23.46 + 10.44 SD years (range 6-60 years). Most--95.4 % of the participants had no previous low vision assessment and none--0.0% had used low vision device. Of the participants, 82.4% reported previous eye examination, 33.3% had not used spectacles previously, despite the existing need. Ignorance--88.9% and poor access--8.5% were the main barriers to uptake of vision care services. In Enugu, Nigeria, there is poor awareness and low utilization of vision care services among people with albinism. The identified barriers to vision care access are amenable to awareness creation and logistic change in the provision of appropriate vision care services.

  6. Unrecognized anterior compartment syndrome following ankle fracture surgery: a case report.

    PubMed

    Seyahi, Aksel; Uludag, Serkan; Akman, Senol; Demirhan, Mehmet

    2009-01-01

    A 35-year-old male sustained a lateral malleolar fracture while playing football. The fracture was treated by open reduction and internal fixation with a tourniquet. The next day, the patient returned with pain and swelling of the ankle and was admitted again to the hospital with a suspected diagnosis of cellulitis. Ten hours later, the patient developed the symptoms of anterior compartment syndrome. Emergency open fasciotomy of the anterior compartment was performed. The retrospective analysis of the patient's history was suggestive of a predisposition to an exercise-induced compartment syndrome. We think that exertional increase of the compartmental pressure before the injury and the tourniquet used during surgery contributed together to the development of compartment syndrome. Physicians should be vigilant in identifying the features of compartment syndrome when managing patients injured during a sporting activity.

  7. 75 FR 76056 - FEDERAL REGISTER CITATION OF PREVIOUS ANNOUNCEMENT:

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ... SECURITIES AND EXCHANGE COMMISSION Sunshine Act Meeting FEDERAL REGISTER CITATION OF PREVIOUS ANNOUNCEMENT: STATUS: Closed meeting. PLACE: 100 F Street, NE., Washington, DC. DATE AND TIME OF PREVIOUSLY ANNOUNCED MEETING: Thursday, December 9, 2010 at 2 p.m. CHANGE IN THE MEETING: Time change. The closed...

  8. The effect of previous traumatic injury on homicide risk.

    PubMed

    Griffin, Russell L; Davis, Gregory G; Levitan, Emily B; MacLennan, Paul A; Redden, David T; McGwin, Gerald

    2014-07-01

    Research has reported that a strong risk factor for traumatic injury is having a previous injury (i.e., recidivism). To date, the only study examining the relationship between recidivism and homicide reported strong associations, but was limited by possible selection bias. The current matched case-control study utilized coroner's data from 2004 to 2008. Subjects were linked to trauma registry data to determine whether the person had a previous traumatic injury. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between homicide and recidivism. Homicide risk was increased for those having a previous traumatic injury (OR 1.81, 95% CI 1.09-2.99) or a previous intentional injury (OR 2.53, 95% CI 1.24-5.17). These results suggest an association between homicide and injury recidivism, and that trauma centers may be an effective setting for screening individuals for secondary prevention efforts of homicide through violence prevention programs. © 2014 American Academy of Forensic Sciences.

  9. Three novel approaches to structural identifiability analysis in mixed-effects models.

    PubMed

    Janzén, David L I; Jirstrand, Mats; Chappell, Michael J; Evans, Neil D

    2016-05-06

    Structural identifiability is a concept that considers whether the structure of a model together with a set of input-output relations uniquely determines the model parameters. In the mathematical modelling of biological systems, structural identifiability is an important concept since biological interpretations are typically made from the parameter estimates. For a system defined by ordinary differential equations, several methods have been developed to analyse whether the model is structurally identifiable or otherwise. Another well-used modelling framework, which is particularly useful when the experimental data are sparsely sampled and the population variance is of interest, is mixed-effects modelling. However, established identifiability analysis techniques for ordinary differential equations are not directly applicable to such models. In this paper, we present and apply three different methods that can be used to study structural identifiability in mixed-effects models. The first method, called the repeated measurement approach, is based on applying a set of previously established statistical theorems. The second method, called the augmented system approach, is based on augmenting the mixed-effects model to an extended state-space form. The third method, called the Laplace transform mixed-effects extension, is based on considering the moment invariants of the systems transfer function as functions of random variables. To illustrate, compare and contrast the application of the three methods, they are applied to a set of mixed-effects models. Three structural identifiability analysis methods applicable to mixed-effects models have been presented in this paper. As method development of structural identifiability techniques for mixed-effects models has been given very little attention, despite mixed-effects models being widely used, the methods presented in this paper provides a way of handling structural identifiability in mixed-effects models previously not

  10. Buried penis: An unrecognized risk factor in the development of invasive penile cancer.

    PubMed

    Abdulla, Alym; Daya, Dean; Pinthus, Jehonathan; Davies, Timothy

    2012-10-01

    One of the documented benefits of neonatal circumcision is protection against invasive penile cancer. To date there have been a handful of published cases of invasive penile cancer in men circumcised as neonates. We report a case of a 73-year-old man, with a history of neonatal circumcision with no evidence of previous human papillomavirus exposure, who developed a buried penis secondary to obesity. He was diagnosed with Grade 2, pT3N0 squamous cell carcinoma of the penis. This report suggests that buried penis may pose a risk factor for the development of penile cancer despite the protective effects of neonatal circumcision. Thus periodic examination of a buried penis is warranted even in patients with no risk factors for penile cancer. A review of the literature is provided.

  11. Previously Identified Deficiencies Not Corrected in the General Fund Enterprise Business System Program

    DTIC Science & Technology

    2011-06-15

    Army AAA Report No. A-2009-0226- FFM , “Examination of Federal Financial Management Improvement Act Compliance - Test Validation General Fund Enterprise...Business System Release 1.2,” September 30, 2009 AAA Report No. A-2009-0231- FFM , “General Fund Enterprise Business System - Federal Financial...Management Improvement Act Compliance Examination of Release 1.3 Functionality,” September 30, 2009 AAA Report No. A-2009-0232- FFM , “General Fund

  12. 5 CFR 532.405 - Use of highest previous rate.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Use of highest previous rate. 532.405 Section 532.405 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PREVAILING RATE SYSTEMS Pay Administration § 532.405 Use of highest previous rate. (a)(1) Subject to the...

  13. 28 CFR 10.5 - Incorporation of papers previously filed.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Incorporation of papers previously filed... CARRYING ON ACTIVITIES WITHIN THE UNITED STATES Registration Statement § 10.5 Incorporation of papers previously filed. Papers and documents already filed with the Attorney General pursuant to the said act and...

  14. 28 CFR 10.5 - Incorporation of papers previously filed.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Incorporation of papers previously filed... CARRYING ON ACTIVITIES WITHIN THE UNITED STATES Registration Statement § 10.5 Incorporation of papers previously filed. Papers and documents already filed with the Attorney General pursuant to the said act and...

  15. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  16. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  17. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  18. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  19. 27 CFR 26.55 - Previously approved formulas.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LIQUORS AND ARTICLES FROM PUERTO RICO AND THE VIRGIN ISLANDS Formulas for Products From Puerto Rico § 26.55 Previously approved formulas. Any formula approved on Form...

  20. Cathodoluminescent bimineralic ooids from the Pleistocene of the Florida continental shelf

    USGS Publications Warehouse

    Major, R. P.; Halley, Robert B.; Lukas, Karen J.

    1988-01-01

      The ooid grainstone underwent an episode of meteoric diagenesis. but ooid cortices were not affected by the event. We propose a previously unrecognized process by which the magnesian calcite cortex layers underwent diagenetic alteration in oxygen-depleted seawater. During this diagenesis, magnesium was lost and manganese was incorporated without apparent textural alteration and without mineralogical stabilization. Thus, we Suggest that cathodoluminescence may result from diagenetic alteration on the sea-floor.

  1. HIV risk-taking behaviour among injecting drug users currently, previously and never enrolled in methadone treatment.

    PubMed

    Baker, A; Kochan, N; Dixon, J; Wodak, A; Heather, N

    1995-04-01

    This study compares the injecting and sexual risk-taking behaviour among injecting drug users (IDUs) currently, previously and never enrolled in methadone maintenance treatment (MMT). All subjects had injected during the 6 months prior to the day of interview. The current MMT group showed significantly lower injecting risk-taking behaviour subscale scores on the HIV Risk-taking Behaviour Scale (HRBS) of the Opiate Treatment Index than the previous MMT and non-MMT groups together. The current MMT group differed from the other two groups in the frequency of injecting and cleaning of injection equipment with bleach. There was no difference between the current MMT group and the other two groups combined in sexual risk-taking behaviour scores on the HRBS. There were no differences between the previous MMT and non-MMT groups in injecting and sexual risk-taking behaviour. HIV seroprevalence was low and there was no difference in seroprevalence between groups. Thus, IDUs currently enrolled in MMT are at reduced risk for HIV infection when compared with IDUs who have previously or never been enrolled in MMT. However, the absence of a difference between the current MMT and other two groups in frequency of sharing behaviours suggests the need for additional strategies among MMT clients to reduce needle-sharing. Possible strategies include the application of relapse prevention interventions and the availability of sterile injecting equipment in MMT clinics. Further research is needed to identify factors which increase attraction and retention of IDUs to MMT.

  2. Identifying Balance Measures Most Likely to Identify Recent Falls.

    PubMed

    Criter, Robin E; Honaker, Julie A

    2016-01-01

    Falls sustained by older adults are an increasing health care issue. Early identification of those at risk for falling can lead to successful prevention of falls. Balance complaints are common among individuals who fall or are at risk for falling. The purpose of this study was to evaluate the clinical utility of a multifaceted balance protocol used for fall risk screening, with the hypothesis that this protocol would successfully identify individuals who had a recent fall (within the previous 12 months). This is a retrospective review of 30 individuals who self-referred for a free fall risk screening. Measures included case history, Activities-Specific Balance Confidence Scale, modified Clinical Test of Sensory Interaction on Balance, Timed Up and Go test, and Dynamic Visual Acuity. Statistical analyses were focused on the ability of the test protocol to identify a fall within the past 12 months and included descriptive statistics, clinical utility indices, logistic regression, receiver operating characteristic curve, area under the curve analysis, effect size (Cohen d), and Spearman correlation coefficients. All individuals who self-referred for this free screening had current imbalance complaints, and were typically women (70%), had a mean age of 77.2 years, and had a fear of falling (70%). Almost half (46.7%) reported at least 1 lifetime fall and 40.0% within the past 12 months. Regression analysis suggested that the Timed Up and Go test was the most important indicator of a recent fall. A cutoff score of 12 or more seconds was optimal (sensitivity: 83.3%; specificity: 61.1%). Older adults with current complaints of imbalance have a higher rate of falls, fall-related injury, and fear of falling than the general community-dwelling public. The Timed Up and Go test is useful for determining recent fall history in individuals with imbalance.

  3. SPARQL-enabled identifier conversion with Identifiers.org

    PubMed Central

    Wimalaratne, Sarala M.; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-01-01

    Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: sarala@ebi.ac.uk PMID:25638809

  4. SPARQL-enabled identifier conversion with Identifiers.org.

    PubMed

    Wimalaratne, Sarala M; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-06-01

    On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. © The Author 2015. Published by Oxford University Press.

  5. No discrimination against previous mates in a sexually cannibalistic spider

    NASA Astrophysics Data System (ADS)

    Fromhage, Lutz; Schneider, Jutta M.

    2005-09-01

    In several animal species, females discriminate against previous mates in subsequent mating decisions, increasing the potential for multiple paternity. In spiders, female choice may take the form of selective sexual cannibalism, which has been shown to bias paternity in favor of particular males. If cannibalistic attacks function to restrict a male's paternity, females may have little interest to remate with males having survived such an attack. We therefore studied the possibility of female discrimination against previous mates in sexually cannibalistic Argiope bruennichi, where females almost always attack their mate at the onset of copulation. We compared mating latency and copulation duration of males having experienced a previous copulation either with the same or with a different female, but found no evidence for discrimination against previous mates. However, males copulated significantly shorter when inserting into a used, compared to a previously unused, genital pore of the female.

  6. Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain.

    PubMed

    Nakamuta, Shinichi; Yang, Yu-Ting; Wang, Chia-Lin; Gallo, Nicholas B; Yu, Jia-Ray; Tai, Yilin; Van Aelst, Linda

    2017-12-04

    Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase-RhoA-interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. © 2017 Nakamuta et al.

  7. Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain

    PubMed Central

    Yang, Yu-Ting; Yu, Jia-Ray; Tai, Yilin

    2017-01-01

    Throughout life, stem cells in the ventricular–subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts’ morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase–RhoA–interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. PMID:29089377

  8. Iron-absorption band analysis for the discrimination of iron-rich zones

    NASA Technical Reports Server (NTRS)

    Rowan, L. C. (Principal Investigator)

    1973-01-01

    The author has identified the following significant results. Study has concentrated on the two primary aspects of the project, structural analysis through evaluation of lineaments and circular features and spectral analyses through digital computer-processing techniques. Several previously unrecognized lineaments are mapped which may be the surface manifestations of major fault or fracture zones. Two of these, the Walker Lane and the Midas Trench lineament system, transect the predominantly NNE-NNW-trending moutain ranges for more than 500 km. Correlation of major lineaments with productive mining districts implies a genetic relationship, the 50 circular or elliptical features delineated suggest a related role for Tertiary volcanism. Color-ratio composites have been used to identify limonitic zones and to discriminate mafic and felsic rock by combing diazo color transparencies of three different ratios. EROS Data Center scene identification number for color composite in this report is ER 1 CC 500. Refinement of enhancement procedures for the ratio images is progressing. Fieldwork in coordination with both spectral and structural analyses is underway.

  9. Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes.

    PubMed

    Markstein, Michele; Pitsouli, Chrysoula; Villalta, Christians; Celniker, Susan E; Perrimon, Norbert

    2008-04-01

    A major obstacle to creating precisely expressed transgenes lies in the epigenetic effects of the host chromatin that surrounds them. Here we present a strategy to overcome this problem, employing a Gal4-inducible luciferase assay to systematically quantify position effects of host chromatin and the ability of insulators to counteract these effects at phiC31 integration loci randomly distributed throughout the Drosophila genome. We identify loci that can be exploited to deliver precise doses of transgene expression to specific tissues. Moreover, we uncover a previously unrecognized property of the gypsy retrovirus insulator to boost gene expression to levels severalfold greater than at most or possibly all un-insulated loci, in every tissue tested. These findings provide the first opportunity to create a battery of transgenes that can be reliably expressed at high levels in virtually any tissue by integration at a single locus, and conversely, to engineer a controlled phenotypic allelic series by exploiting several loci. The generality of our approach makes it adaptable to other model systems to identify and modify loci for optimal transgene expression.

  10. An integrated proteomic approach uncovers novel substrates and functions of the Lon protease in Escherichia coli.

    PubMed

    Arends, Jan; Griego, Marcena; Thomanek, Nikolas; Lindemann, Claudia; Kutscher, Blanka; Meyer, Helmut E; Narberhaus, Franz

    2018-04-30

    Controlling the cellular abundance and proper function of proteins by proteolysis is a universal process in all living organisms. In Escherichia coli, the ATP-dependent Lon protease is crucial for protein quality control and regulatory processes. To understand how diverse substrates are selected and degraded, unbiased global approaches are needed. We employed a quantitative Super-SILAC mass spectrometry approach and compared the proteomes of a lon mutant and a strain producing the protease to discover Lon-dependent physiological functions. To identify Lon substrates, we took advantage of a Lon trapping variant, which is able to translocate substrates but unable to degrade them. Lon-associated proteins were identified by label-free LC-MS/MS. The combination of both approaches revealed a total of 14 novel Lon substrates. Besides the identification of known pathways affected by Lon, for example the superoxide-stress response, our cumulative data suggests previously unrecognized fundamental functions of Lon in sulfur assimilation, nucleotide biosynthesis, amino acid and central energy metabolism. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Identifying targets for improvement in nighttime seat belt use : traffic tech.

    DOT National Transportation Integrated Search

    2010-07-01

    Previous research has found that the proportion of unbelted : fatalities is greater at night than during the day. Failure to use : seat belts has been identified as an important factor in nighttime : fatalities, yet there are still many gaps in our k...

  12. Elective repeat caesarean section versus induction of labour for women with a previous caesarean birth.

    PubMed

    Dodd, Jodie M; Crowther, Caroline A; Grivell, Rosalie M; Deussen, Andrea R

    2014-12-19

    When a woman has had a previous caesarean birth and requires induction of labour in a subsequent pregnancy there are two options for her care, an elective repeat caesarean or planned induction of labour. While there are risks and benefits for both elective repeat caesarean birth and planned induction of labour, current sources of information are limited to non-randomised cohort studies. Studies designed in this way have significant potential for bias and consequently any conclusions based on these results are limited in their reliability and should be interpreted with caution. To assess, using the best available evidence, the benefits and harms of elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth, who require induction of labour in a subsequent pregnancy. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (31 October 2014). Randomised controlled trials with reported data that compared outcomes in mothers and babies for women who planned an elective repeat caesarean section with outcomes in women who planned induction of labour, where a previous birth had been by caesarean. There was no data extraction performed. There were no randomised controlled trials identified. Both planned elective repeat caesarean section and planned induction of labour for women with a prior caesarean birth are associated with benefits and harms. Evidence for these care practices is drawn from non-randomised studies that are associated with potential bias. Any results and conclusions must therefore be interpreted with caution. Randomised controlled trials are required to provide the most reliable evidence regarding the benefits and harms of both planned elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth.

  13. A previous hamstring injury affects kicking mechanics in soccer players.

    PubMed

    Navandar, Archit; Veiga, Santiago; Torres, Gonzalo; Chorro, David; Navarro, Enrique

    2018-01-10

    Although the kicking skill is influenced by limb dominance and sex, how a previous hamstring injury affects kicking has not been studied in detail. Thus, the objective of this study was to evaluate the effect of sex and limb dominance on kicking in limbs with and without a previous hamstring injury. 45 professional players (males: n=19, previously injured players=4, age=21.16 ± 2.00 years; females: n=19, previously injured players=10, age=22.15 ± 4.50 years) performed 5 kicks each with their preferred and non-preferred limb at a target 7m away, which were recorded with a three-dimensional motion capture system. Kinematic and kinetic variables were extracted for the backswing, leg cocking, leg acceleration and follow through phases. A shorter backswing (20.20 ± 3.49% vs 25.64 ± 4.57%), and differences in knee flexion angle (58 ± 10o vs 72 ± 14o) and hip flexion velocity (8 ± 0rad/s vs 10 ± 2rad/s) were observed in previously injured, non-preferred limb kicks for females. A lower peak hip linear velocity (3.50 ± 0.84m/s vs 4.10 ± 0.45m/s) was observed in previously injured, preferred limb kicks of females. These differences occurred in the backswing and leg-cocking phases where the hamstring muscles were the most active. A variation in the functioning of the hamstring muscles and that of the gluteus maximus and iliopsoas in the case of a previous injury could account for the differences observed in the kicking pattern. Therefore, the effects of a previous hamstring injury must be considered while designing rehabilitation programs to re-educate kicking movement.

  14. Subsequent childbirth after a previous traumatic birth.

    PubMed

    Beck, Cheryl Tatano; Watson, Sue

    2010-01-01

    Nine percent of new mothers in the United States who participated in the Listening to Mothers II Postpartum Survey screened positive for meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for posttraumatic stress disorder after childbirth. Women who have had a traumatic birth experience report fewer subsequent children and a longer length of time before their second baby. Childbirth-related posttraumatic stress disorder impacts couples' physical relationship, communication, conflict, emotions, and bonding with their children. The purpose of this study was to describe the meaning of women's experiences of a subsequent childbirth after a previous traumatic birth. Phenomenology was the research design used. An international sample of 35 women participated in this Internet study. Women were asked, "Please describe in as much detail as you can remember your subsequent pregnancy, labor, and delivery following your previous traumatic birth." Colaizzi's phenomenological data analysis approach was used to analyze the stories of the 35 women. Data analysis yielded four themes: (a) riding the turbulent wave of panic during pregnancy; (b) strategizing: attempts to reclaim their body and complete the journey to motherhood; (c) bringing reverence to the birthing process and empowering women; and (d) still elusive: the longed-for healing birth experience. Subsequent childbirth after a previous birth trauma has the potential to either heal or retraumatize women. During pregnancy, women need permission and encouragement to grieve their prior traumatic births to help remove the burden of their invisible pain.

  15. Fenofibrate Metabolism in the Cynomolgus Monkey using Ultraperformance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry-Based MetabolomicsS⃞

    PubMed Central

    Liu, Aiming; Patterson, Andrew D.; Yang, Zongtao; Zhang, Xinying; Liu, Wei; Qiu, Fayang; Sun, He; Krausz, Kristopher W.; Idle, Jeffrey R.; Gonzalez, Frank J.; Dai, Renke

    2009-01-01

    Fenofibrate, widely used for the treatment of dyslipidemia, activates the nuclear receptor, peroxisome proliferator-activated receptor α. However, liver toxicity, including liver cancer, occurs in rodents treated with fibrate drugs. Marked species differences occur in response to fibrate drugs, especially between rodents and humans, the latter of which are resistant to fibrate-induced cancer. Fenofibrate metabolism, which also shows species differences, has not been fully determined in humans and surrogate primates. In the present study, the metabolism of fenofibrate was investigated in cynomolgus monkeys by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS)-based metabolomics. Urine samples were collected before and after oral doses of fenofibrate. The samples were analyzed in both positive-ion and negative-ion modes by UPLC-QTOFMS, and after data deconvolution, the resulting data matrices were subjected to multivariate data analysis. Pattern recognition was performed on the retention time, mass/charge ratio, and other metabolite-related variables. Synthesized or purchased authentic compounds were used for metabolite identification and structure elucidation by liquid chromatographytandem mass spectrometry. Several metabolites were identified, including fenofibric acid, reduced fenofibric acid, fenofibric acid ester glucuronide, reduced fenofibric acid ester glucuronide, and compound X. Another two metabolites (compound B and compound AR), not previously reported in other species, were characterized in cynomolgus monkeys. More importantly, previously unknown metabolites, fenofibric acid taurine conjugate and reduced fenofibric acid taurine conjugate were identified, revealing a previously unrecognized conjugation pathway for fenofibrate. PMID:19251819

  16. In the Information Age, do dementia caregivers get the information they need? Semi-structured interviews to determine informal caregivers' education needs, barriers, and preferences.

    PubMed

    Peterson, Kendra; Hahn, Howard; Lee, Amber J; Madison, Catherine A; Atri, Alireza

    2016-09-23

    Most patients with dementia or cognitive impairment receive care from family members, often untrained for this challenging role. Caregivers may not access publicly available caregiving information, and caregiver education programs are not widely implemented clinically. Prior large surveys yielded broad quantitative understanding of caregiver information needs, but do not illuminate the in-depth, rich, and nuanced caregiver perspectives that can be gleaned using qualitative methodology. We aimed to understand perspectives about information sources, barriers and preferences, through semi-structured interviews with 27 caregivers. Content analysis identified important themes. We interviewed 19 women, 8 men; mean age 58.5 years; most adult children (15) or spouses (8) of the care recipient. Dementia symptoms often developed insidiously, with delayed disease acknowledgement and caregiver self-identification. While memory loss was common, behavioral symptoms were most troublesome, often initially unrecognized as disease indicators. Emerging themes: 1.) Barriers to seeking information often result from knowledge gaps, rather than reluctance to assume the caregiver role; 2.) Most caregivers currently receive insufficient information. Caregivers are open to many information sources, settings, and technologies, including referrals to other healthcare professionals, print material, and community and internet resources, but expect the primary care provider (PCP) to recommend, endorse, and guide them to specific sources. These findings replicated and expanded on results from previous quantitative surveys and, importantly, revealed a previously unrecognized essential factor: despite receiving insufficient information, caregivers place critical value on their relationship with care recipient PCPs to receive recommendations, guidance and endorsement to sources of caregiving information. Implications include: 1.) Greater public education is needed to help caregivers identify and

  17. Sun exposure habits and health risk-related behaviours among individuals with previous history of skin cancer.

    PubMed

    Falk, Magnus; Faresjö, Ashild; Faresjö, Tomas

    2013-02-01

    The aim of the present study was to investigate possible associations between UV exposure and other health risk behaviours in different social environments and in regard to previous history of skin cancer. In two closely-located, equally-sized cities in Sweden, representing different social environments (blue collar and white collar), patients aged 55-69 years, diagnosed with skin cancer (study group, n=489) or seborrhoeic keratosis (control group, n=664), were identified through a regional Health Care Register, and were given a questionnaire mapping for sun habits, tobacco smoking, alcohol use, and physical activity. A previous history of skin cancer was associated with reduced UV exposure (p<0.01) and increased UV protection (p<0.001), higher alcohol consumption (p<0.05), and higher level of physical activity (p<0.05). Smoking was more common among subjects frequently sunbathing and rarely using sunscreen, but frequent sunbathing was positively associated with physical activity (p<0.05). Daily smoking and risky drinking habits were more common in the blue collar social environment, while no differences were seen for sun habits in this respect. A previous history of skin cancer appears to promote increased UV protection. In contrast to alcohol/smoking habits, no association between social environment and sun habits was found.

  18. Exploring the SDSS Dataset with Linked Scatter Plots: I. EMP, CEMP, and CV Stars

    NASA Technical Reports Server (NTRS)

    Carbon, Duane F.; Henze, Christopher; Nelson, Bron C.

    2017-01-01

    We present the results of a search for EMP, CEMP, and cataclysmic variable stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets and can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct a search for EMP, CEMP, and cataclysmic variable stars in the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, C-rich EMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature.

  19. Owls may use faeces and prey feathers to signal current reproduction.

    PubMed

    Penteriani, Vincenzo; Delgado, Maria del Mar

    2008-08-20

    Many animals communicate by marking focal elements of their home range with different kinds of materials. Visual signaling has been demonstrated to play a previously unrecognized role in the intraspecific communication of eagle owls (Bubo bubo), in both territorial and parent-offspring contexts. Visual signals may play a role in a variety of circumstances in this crepuscular and nocturnal species. Here, we report that a large amount of extremely visible white faeces and prey feathers appear during the breeding season on posts and plucking sites in proximity to the nest, potentially representing a way for eagle owls to mark their territory. We present descriptive and experimental evidence showing that faeces and prey remains could act as previously unrecognized visual signals in a nocturnal avian predator. This novel signaling behavior could indicate the owls' current reproductive status to potential intruders, such as other territorial owls or non-breeding floaters. Faeces and prey feather markings may also advertise an owl's reproductive status or function in mate-mate communication. We speculate that faeces marks and plucking may represent an overlooked but widespread method for communicating current reproduction to conspecifics. Such marking behavior may be common in birds, and we may now be exploring other questions and mechanisms in territoriality.

  20. Exploring the SDSS Dataset with Linked Scatter Plots: I. EMP, CEMP, and CV Stars.

    PubMed

    Carbon, Duane F; Henze, Christopher; Nelson, Bron C

    2017-02-01

    We present the results of a search for EMP, CEMP, and cataclysmic variable stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets and can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct a search for EMP, CEMP, and cataclysmic variable stars in the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, C-rich EMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature.

  1. Exploring the SDSS Data Set with Linked Scatter Plots. I. EMP, CEMP, and CV Stars

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carbon, Duane F.; Henze, Christopher; Nelson, Bron C., E-mail: Duane.F.Carbon@nasa.gov

    We present the results of a search for extremely metal-poor (EMP), carbon-enhanced metal-poor (CEMP), and cataclysmic variable (CV) stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets, and it can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct our search using the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSSmore » stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, CEMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He ii emission CV stars found by the LSP approach that have not yet been discussed in the literature.« less

  2. Owls May Use Faeces and Prey Feathers to Signal Current Reproduction

    PubMed Central

    Penteriani, Vincenzo; del Mar Delgado, Maria

    2008-01-01

    Background Many animals communicate by marking focal elements of their home range with different kinds of materials. Visual signaling has been demonstrated to play a previously unrecognized role in the intraspecific communication of eagle owls (Bubo bubo), in both territorial and parent-offspring contexts. Visual signals may play a role in a variety of circumstances in this crepuscular and nocturnal species. Methodology/Principal Findings Here, we report that a large amount of extremely visible white faeces and prey feathers appear during the breeding season on posts and plucking sites in proximity to the nest, potentially representing a way for eagle owls to mark their territory. We present descriptive and experimental evidence showing that faeces and prey remains could act as previously unrecognized visual signals in a nocturnal avian predator. This novel signaling behavior could indicate the owls' current reproductive status to potential intruders, such as other territorial owls or non-breeding floaters. Faeces and prey feather markings may also advertise an owl's reproductive status or function in mate-mate communication. Conclusions/Significance We speculate that faeces marks and plucking may represent an overlooked but widespread method for communicating current reproduction to conspecifics. Such marking behavior may be common in birds, and we may now be exploring other questions and mechanisms in territoriality. PMID:18714382

  3. VizieR Online Data Catalog: Exploring the SDSS data set. I. EMP & CV stars (Carbon+, 2017)

    NASA Astrophysics Data System (ADS)

    Carbon, D. F.; Henze, C.; Nelson, B. C.

    2017-08-01

    We present the results of a search for extremely metal-poor (EMP), carbon-enhanced metal-poor (CEMP), and cataclysmic variable (CV) stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets, and it can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct our search using the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, CEMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature. (3 data files).

  4. Exploring the SDSS Dataset with Linked Scatter Plots: I. EMP, CEMP, and CV Stars

    PubMed Central

    Carbon, Duane F.; Henze, Christopher; Nelson, Bron C.

    2017-01-01

    We present the results of a search for EMP, CEMP, and cataclysmic variable stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets and can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct a search for EMP, CEMP, and cataclysmic variable stars in the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, C-rich EMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature. PMID:28684884

  5. Exploring the SDSS Data Set with Linked Scatter Plots. I. EMP, CEMP, and CV Stars

    NASA Astrophysics Data System (ADS)

    Carbon, Duane F.; Henze, Christopher; Nelson, Bron C.

    2017-02-01

    We present the results of a search for extremely metal-poor (EMP), carbon-enhanced metal-poor (CEMP), and cataclysmic variable (CV) stars using a new exploration tool based on linked scatter plots (LSPs). Our approach is especially designed to work with very large spectrum data sets such as the SDSS, LAMOST, RAVE, and Gaia data sets, and it can be applied to stellar, galaxy, and quasar spectra. As a demonstration, we conduct our search using the SDSS DR10 data set. We first created a 3326-dimensional phase space containing nearly 2 billion measures of the strengths of over 1600 spectral features in 569,738 SDSS stars. These measures capture essentially all the stellar atomic and molecular species visible at the resolution of SDSS spectra. We show how LSPs can be used to quickly isolate and examine interesting portions of this phase space. To illustrate, we use LSPs coupled with cuts in selected portions of phase space to extract EMP stars, CEMP stars, and CV stars. We present identifications for 59 previously unrecognized candidate EMP stars and 11 previously unrecognized candidate CEMP stars. We also call attention to 2 candidate He II emission CV stars found by the LSP approach that have not yet been discussed in the literature.

  6. Ancestry-based stratified analysis of Immunochip data identifies novel associations with celiac disease.

    PubMed

    Garcia-Etxebarria, Koldo; Jauregi-Miguel, Amaia; Romero-Garmendia, Irati; Plaza-Izurieta, Leticia; Legarda, Maria; Irastorza, Iñaki; Bilbao, Jose Ramon

    2016-12-01

    To identify candidate genes in celiac disease (CD), we reanalyzed the whole Immunochip CD cohort using a different approach that clusters individuals based on immunoancestry prior to disease association analysis, rather than by geographical origin. We detected 636 new associated SNPs (P<7.02 × 10 -07 ) and identified 5 novel genomic regions, extended 8 others previously identified and also detected 18 isolated signals defined by one or very few significant SNPs. To test whether we could identify putative candidate genes, we performed expression analyses of several genes from the top novel region (chr2:134533564-136169524), from a previously identified locus that is now extended, and a gene marked by an isolated SNP, in duodenum biopsies of active and treated CD patients, and non-celiac controls. In the largest novel region, CCNT2 and R3HDM1 were constitutively underexpressed in disease, even after gluten removal. Moreover, several genes within this region were coexpressed in patients, but not in controls. Other novel genes like KIF21B, REL and SORD also showed altered expression in active disease. Apart from the identification of novel CD loci, these results suggest that ancestry-based stratified analysis is an efficient strategy for association studies in complex diseases.

  7. Rasburicase-induced Hemolytic Anemia in an Adolescent With Unknown Glucose-6-Phosphate Dehydrogenase Deficiency.

    PubMed

    Akande, Manzilat; Audino, Anthony N; Tobias, Joseph D

    2017-01-01

    Rasburicase, used in the prevention and treatment of tumor lysis syndrome (TLS), may cause hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Although routine screening for G6PD deficiency has been recommended, given the turnaround time for test results and the urgency to treat TLS, such screening may not be feasible. We report a case of rasburicase-induced hemolytic anemia without methemoglobinemia in an adolescent with T-cell lymphoblastic lymphoma, TLS, and previously unrecognized G6PD deficiency. Previous reports of hemolytic anemia with rasburicase are reviewed, mechanisms discussed, and preventative strategies presented.

  8. Bipolar affective disorder and Parkinson's disease: a rare, insidious and often unrecognized association.

    PubMed

    Cannas, A; Spissu, A; Floris, G L; Congia, S; Saddi, M V; Melis, M; Mascia, M M; Pinna, F; Tuveri, A; Solla, P; Milia, A; Giagheddu, M; Tacconi, P

    2002-09-01

    Five patients (4 women) with Parkinson's disease (PD) and primary major psychiatric disorder (PMPD) meeting DSM-IV criteria for the diagnosis of bipolar affective disorder (BAD) were studied. Four patients had early onset PD. Four developed a severe psychiatric disorder a few years after starting dopaminergic therapy in presence of a mild motor disability and a mild cognitive impairment, with no evidence of cerebral atrophy at CT or MRI. Two patients developed a clear manic episode; the other three presented a severe depressive episode (in one case featuring a Cotard syndrome). None showed previous signs of long term L-dopa treatment syndrome (LTS), hallucinosis or other minor psychiatric disorders. The two manic episodes occurred shortly after an increase of dopaminergic therapy and in one case rapid cyclic mood fluctuations were observed. At the onset of psychiatric symptoms, all patients had an unspecific diagnosis of chronic delusional hallucinatory psychosis (CDHP).

  9. Methanotrophic bacteria in warm geothermal spring sediments identified using stable-isotope probing.

    PubMed

    Sharp, Christine E; Martínez-Lorenzo, Azucena; Brady, Allyson L; Grasby, Stephen E; Dunfield, Peter F

    2014-10-01

    We investigated methanotrophic bacteria in sediments of several warm geothermal springs ranging in temperature from 22 to 45 °C. Methane oxidation was measured at potential rates up to 141 μmol CH4 d(-1) g(-1) sediment. Active methanotrophs were identified using (13) CH4 stable-isotope probing (SIP) incubations performed at close to in situ temperatures for each site. Quantitative (q) PCR of pmoA genes identified the position of the heavy ((13) C-labelled) DNA fractions in density gradients, and 16S rRNA gene pyrotag sequencing of the heavy fractions was performed to identify the active methanotrophs. Methanotroph communities identified in heavy fractions of all samples were predominated by species similar (≥ 95% 16S rRNA gene identities) to previously characterized Gammaproteobacteria and Alphaproteobacteria methanotrophs. Among the five hottest samples (45 °C), members of the Gammaproteobacteria genus Methylocaldum dominated in two cases, while three others were dominated by an OTU closely related (96.8% similarity) to the Alphaproteobacteria genus Methylocapsa. These results suggest that diverse methanotroph groups are adapted to warm environments, including the Methylocapsa-Methylocella-Methyloferula group, which has previously only been detected in cooler sites. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  10. Hypoxia induces copper stable isotope fractionation in hepatocellular carcinoma, in a HIF-independent manner.

    PubMed

    Bondanese, Victor P; Lamboux, Aline; Simon, Melanie; Lafont, Jérôme E; Albalat, Emmanuelle; Pichat, Sylvain; Vanacker, Jean-Marc; Telouk, Philippe; Balter, Vincent; Oger, Philippe; Albarède, Francis

    2016-11-09

    Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, with increasing incidence worldwide. The unrestrained proliferation of tumour cells leads to tumour hypoxia which in turn promotes cancer aggressiveness. While changes in the concentration of copper (Cu) have long been observed upon cancerization, we have recently reported that the isotopic composition of copper is also altered in several types of cancer. In particular, we showed that in hepatocellular carcinoma, tumour tissue contains heavier copper compared to the surrounding parenchyma. However, the reasons behind such isotopic signature remained elusive. Here we show that hypoxia causes heavy copper enrichment in several human cell lines. We also demonstrate that this effect of hypoxia is pH, HIF-1 and -2 independent. Our data identify a previously unrecognized cellular process associated with hypoxia, and suggests that in vivo tumour hypoxia determines copper isotope fractionation in HCC and other solid cancers.

  11. Multidrug Transport Protein NorM from Vibrio cholerae Simultaneously Couples to Sodium- and Proton-Motive Force*

    PubMed Central

    Jin, Yoonhee; Nair, Asha; van Veen, Hendrik W.

    2014-01-01

    Membrane transporters belonging to the multidrug and toxic compound extrusion family mediate the efflux of unrelated pharmaceuticals from the interior of the cell in organisms ranging from bacteria to human. These proteins are thought to fall into two classes that couple substrate efflux to the influx of either Na+ or H+. We studied the energetics of drug extrusion by NorM from Vibrio cholerae in proteoliposomes in which purified NorM protein was functionally reconstituted in an inside-out orientation. We establish that NorM simultaneously couples to the sodium-motive force and proton-motive force, and biochemically identify protein regions and residues that play important roles in Na+ or H+ binding. As the positions of protons are not available in current medium and high-resolution crystal structures of multidrug and toxic compound extrusion transporters, our findings add a previously unrecognized parameter to mechanistic models based of these structures. PMID:24711447

  12. A non cool-core 4.6-keV cluster around the bright nearby radio galaxy PKS B1416-493

    NASA Astrophysics Data System (ADS)

    Worrall, D. M.; Birkinshaw, M.

    2017-05-01

    We present new X-ray (Chandra) and radio (ATCA) observations of the z = 0.09 radio galaxy PKS B1416-493, a member of the southern equivalent of the 3CRR sample. We find the source to be embedded in a previously unrecognized bright kT = 4.6-keV non cool-core cluster. The discovery of new clusters of such high temperature and luminosity within z = 0.1 is rare. The radio source was chosen for observation based on its intermediate FR I/II morphology. We identify a cavity coincident with the northeast lobe, and excess counts associated with the southwest lobe that we interpret as inverse-Compton X-ray emission. The jet power, at 5.3 × 1044 erg s-1, when weighted by radio source density, supports suggestions that radio sources of intermediate morphology and radio power may dominate radio-galaxy heating in the local Universe.

  13. [Adolescents previously involved in Satanism: mental health problems experience].

    PubMed

    Heathcote, H; Gmeiner, A; Poggenpoel, M

    1998-03-01

    As far as the phenomena of adolescents previously involved with satanism that experience obstacles in the strive for mental health, no research has previously been done. Adolescents previously involved in satanism, presents behaviour problems like aggressive outbursts depression, "psychosis", or suicide attempts that can even lead to suicide. In the phenomena-analysis semi-structured, phenomenological interviews with the respondents and their parents, were performed. The respondents were requested to write a naive sketch about there life. After the data-control was done, guidelines for nursing staff had been set. The guidelines are set for the management of adolescents that has previously been involved in satanism, and experiences obstacles in their strive for mental health. Interviews with experts in satanism was done, literature in the form of books, magazines and newsclippings were used to verify the findings in the research. The most important guidelines are that: the caregivers have to be reborn Christians; they are not allowed to show, any fear or sympathy; they have to have sufficient knowledge about satanism; the adolescent has to be unconditionally accepted; the caregivers have to work in a team; the adolescents have to be taught to deal with their emotions.

  14. Adolescents previously involved in Satanism experiencing mental health problems.

    PubMed

    Heathcote, H; Gmeiner, A; Poggenpoel, M

    1999-06-01

    No research has previously been done regarding the phenomenon of adolescents who have previously been involved in Satanism and who experience obstacles in their strive for mental health. Adolescents previously involved in Satanism present behavioral problems like aggressive outbursts, depression, "psychosis" or suicide attempts, that could lead to suicide. In the phenomenon-analysis semi-structured, phenomenological interviews were performed with the respondents and their parents. The respondents were requested to write a naïve sketch about their life. After completion of the data-control, guidelines for nursing staff were set. The guidelines are set for the management of adolescents who have previously been involved in Satanism and who experience obstacles in their strive for mental health. Interviews with experts in Satanism were conducted, literature in the form of books, magazines and newspaper-clippings were used to verify the research findings. The most important guidelines are that the caregivers have to be reborn Christians; they are not allowed to show any fear or sympathy; they must have sufficient knowledge about Satanism; the adolescents have to be unconditionally accepted; the caregivers have to work in a team and the adolescents have to be taught to deal with their emotions.

  15. Exome sequencing of a large family identifies potential candidate genes contributing risk to bipolar disorder.

    PubMed

    Zhang, Tianxiao; Hou, Liping; Chen, David T; McMahon, Francis J; Wang, Jen-Chyong; Rice, John P

    2018-03-01

    Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. 31 CFR 202.5 - Previously designated depositaries.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Previously designated depositaries. 202.5 Section 202.5 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE DEPOSITARIES AND FINANCIAL AGENTS...

  17. 31 CFR 202.5 - Previously designated depositaries.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Previously designated depositaries. 202.5 Section 202.5 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE DEPOSITARIES AND FINANCIAL AGENTS...

  18. Meta-analysis identifies common variants associated with body mass index in East Asians

    PubMed Central

    Wen, Wanqing; Cho, Yoon Shin; Zheng, Wei; Dorajoo, Rajkumar; Kato, Norihiro; Qi, Lu; Chen, Chien-Hsiun; Delahanty, Ryan J.; Okada, Yukinori; Tabara, Yasuharu; Gu, Dongfeng; Zhu, Dingliang; Haiman, Christopher A.; Mo, Zengnan; Gao, Yu-Tang; Saw, Seang Mei; Go, Min Jin; Takeuchi, Fumihiko; Chang, Li-Ching; Kokubo, Yoshihiro; Liang, Jun; Hao, Mei; Marchand, Loic Le; Zhang, Yi; Hu, Yanling; Wong, Tien Yin; Long, Jirong; Han, Bok-Ghee; Kubo, Michiaki; Yamamoto, Ken; Su, Mei-Hsin; Miki, Tetsuro; Henderson, Brian E.; Song, Huaidong; Tan, Aihua; He, Jiang; Ng, Daniel P.-K.; Cai, Qiuyin; Tsunoda, Tatsuhiko; Tsai, Fuu-Jen; Iwai, Naoharu; Chen, Gary K.; Shi, Jiajun; Xu, Jianfeng; Sim, Xueling; Xiang, Yong-Bing; Maeda, Shiro; Ong, Rick T.H.; Li, Chun; Nakamura, Yusuke; Aung, Tin; Kamatani, Naoyuki; Liu, Jian Jun; Lu, Wei; Yokota, Mitsuhiro; Seielstad, Mark; Fann, Cathy S.J.; Wu, Jer-Yuarn; Lee, Jong-Young; Hu, Frank B.; Tanaka, Toshihiro; Tai, E. Shyong; Shu, Xiao Ou

    2012-01-01

    Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We conducted a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 East Asians, followed by in silico and de novo replication in 37,691 and 17,642 additional East Asians, respectively. We identified ten BMI-associated loci at the genome-wide significance level (P<5.0×10−8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR/QPCTL, ADCY3/RBJ, BDNF, and MAP2K5) and three novel loci in or near the CDKAL1,PCSK1, and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a new locus near PAX6, which all had P<5.0×10−7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations. PMID:22344219

  19. Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection.

    PubMed

    Yin, Xin; Ying, Dong; Lhomme, Sébastien; Tang, Zimin; Walker, Christopher M; Xia, Ningshao; Zheng, Zizheng; Feng, Zongdi

    2018-05-01

    The enterically transmitted hepatitis E virus (HEV) adopts a unique strategy to exit cells by cloaking its capsid (encoded by the viral ORF2 gene) and circulating in the blood as "quasi-enveloped" particles. However, recent evidence suggests that the majority of the ORF2 protein present in the patient serum and supernatants of HEV-infected cell culture exists in a free form and is not associated with virus particles. The origin and biological functions of this secreted form of ORF2 (ORF2 S ) are unknown. Here we show that production of ORF2 S results from translation initiated at the previously presumed AUG start codon for the capsid protein, whereas translation of the actual capsid protein (ORF2 C ) is initiated at a previously unrecognized internal AUG codon (15 codons downstream of the first AUG). The addition of 15 amino acids to the N terminus of the capsid protein creates a signal sequence that drives ORF2 S secretion via the secretory pathway. Unlike ORF2 C , ORF2 S is glycosylated and exists as a dimer. Nonetheless, ORF2 S exhibits substantial antigenic overlap with the capsid, but the epitopes predicted to bind the putative cell receptor are lost. Consistent with this, ORF2 S does not block HEV cell entry but inhibits antibody-mediated neutralization. These results reveal a previously unrecognized aspect in HEV biology and shed new light on the immune evasion mechanisms and pathogenesis of this virus.

  20. 22 CFR 40.93 - Aliens unlawfully present after previous immigration violation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Aliens unlawfully present after previous... TO BOTH NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.93 Aliens unlawfully present after previous immigration violation. An alien described...

  1. 22 CFR 40.93 - Aliens unlawfully present after previous immigration violation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Aliens unlawfully present after previous... TO BOTH NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.93 Aliens unlawfully present after previous immigration violation. An alien described...

  2. 22 CFR 40.93 - Aliens unlawfully present after previous immigration violation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Aliens unlawfully present after previous... TO BOTH NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.93 Aliens unlawfully present after previous immigration violation. An alien described...

  3. 22 CFR 40.93 - Aliens unlawfully present after previous immigration violation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Aliens unlawfully present after previous... TO BOTH NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.93 Aliens unlawfully present after previous immigration violation. An alien described...

  4. 22 CFR 40.93 - Aliens unlawfully present after previous immigration violation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Aliens unlawfully present after previous... TO BOTH NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Aliens Previously Removed § 40.93 Aliens unlawfully present after previous immigration violation. An alien described...

  5. A decision-theoretic approach to identifying future high-cost patients.

    PubMed

    Pietz, Kenneth; Byrne, Margaret M; Petersen, Laura A

    2006-09-01

    The objective of this study was to develop and evaluate a method of allocating funding for very-high-cost (VHC) patients among hospitals. Diagnostic cost groups (DCGs) were used for risk adjustment. The patient population consisted of 253,013 veterans who used Department of Veterans Affairs (VA) medical care services in fiscal year (FY) 2003 (October 1, 2002-September 30, 2003) in a network of 8 VA hospitals. We defined VHC as greater than 75,000 dollars (0.81%). The upper fifth percentile was also used for comparison. A Bayesian decision rule for classifying patients as VHC/not VHC using DCGs was developed and evaluated. The method uses FY 2003 DCGs to allocate VHC funds for FY 2004. We also used FY 2002 DCGs to allocate VHC funds for FY 2003 for comparison. The resulting allocation was compared with using the allocation of VHC patients among the hospitals in the previous year. The decision rule identified DCG 17 as the optimal cutoff for identifying VHC patients for the next year. The previous year's allocation came closest to the actual distribution of VHC patients. The decision-theoretic approach may provide insight into the economic consequences of classifying a patient as VHC or not VHC. More research is needed into methods of identifying future VHC patients so that capitation plans can fairly reimburse healthcare systems for appropriately treating these patients.

  6. Mask induction despite circuit obstruction: an unrecognized hazard of relying on automated machine check technology.

    PubMed

    Yang, Kamie K; Lewis, Ian H

    2014-06-15

    Various equipment malfunctions of anesthesia gas delivery systems have been previously reported. Our profession increasingly uses technology as a means to prevent these errors. We report a case of a near-total anesthesia circuit obstruction that went undetected before the induction of anesthesia despite the use of automated machine check technology. This case highlights that automated machine check modules can fail to detect severe equipment failure and demonstrates how, even in this era of expanding technology, manual checks still remain essential components of safe care.

  7. Typhoid fever acquired in the United States, 1999–2010: epidemiology, microbiology, and use of a space–time scan statistic for outbreak detection

    PubMed Central

    IMANISHI, M.; NEWTON, A. E.; VIEIRA, A. R.; GONZALEZ-AVILES, G.; KENDALL SCOTT, M. E.; MANIKONDA, K.; MAXWELL, T. N.; HALPIN, J. L.; FREEMAN, M. M.; MEDALLA, F.; AYERS, T. L.; DERADO, G.; MAHON, B. E.; MINTZ, E. D.

    2016-01-01

    SUMMARY Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space–time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space–time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space–time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection. PMID:25427666

  8. Typhoid fever acquired in the United States, 1999-2010: epidemiology, microbiology, and use of a space-time scan statistic for outbreak detection.

    PubMed

    Imanishi, M; Newton, A E; Vieira, A R; Gonzalez-Aviles, G; Kendall Scott, M E; Manikonda, K; Maxwell, T N; Halpin, J L; Freeman, M M; Medalla, F; Ayers, T L; Derado, G; Mahon, B E; Mintz, E D

    2015-08-01

    Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space-time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space-time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space-time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection.

  9. 18 CFR 154.302 - Previously submitted material.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Previously submitted material. 154.302 Section 154.302 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... concurrently with the rate change filing. There must be furnished to the Director, Office of Energy Market...

  10. 18 CFR 366.6 - Previously authorized activities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Previously authorized activities. 366.6 Section 366.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... POWER ACT AND NATURAL GAS ACT BOOKS AND RECORDS Definitions and Provisions Under PUHCA 2005, the Federal...

  11. 18 CFR 366.6 - Previously authorized activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Previously authorized activities. 366.6 Section 366.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... POWER ACT AND NATURAL GAS ACT BOOKS AND RECORDS Definitions and Provisions Under PUHCA 2005, the Federal...

  12. Eight previously unidentified mutations found in the OA1 ocular albinism gene

    PubMed Central

    Mayeur, Hélène; Roche, Olivier; Vêtu, Christelle; Jaliffa, Carolina; Marchant, Dominique; Dollfus, Hélène; Bonneau, Dominique; Munier, Francis L; Schorderet, Daniel F; Levin, Alex V; Héon, Elise; Sutherland, Joanne; Lacombe, Didier; Said, Edith; Mezer, Eedy; Kaplan, Josseline; Dufier, Jean-Louis; Marsac, Cécile; Menasche, Maurice; Abitbol, Marc

    2006-01-01

    Background Ocular albinism type 1 (OA1) is an X-linked ocular disorder characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in pigmented skin and eye cells, and misrouting of the optical tracts. This disease is primarily caused by mutations in the OA1 gene. Methods The ophthalmologic phenotype of the patients and their family members was characterized. We screened for mutations in the OA1 gene by direct sequencing of the nine PCR-amplified exons, and for genomic deletions by PCR-amplification of large DNA fragments. Results We sequenced the nine exons of the OA1 gene in 72 individuals and found ten different mutations in seven unrelated families and three sporadic cases. The ten mutations include an amino acid substitution and a premature stop codon previously reported by our team, and eight previously unidentified mutations: three amino acid substitutions, a duplication, a deletion, an insertion and two splice-site mutations. The use of a novel Taq polymerase enabled us to amplify large genomic fragments covering the OA1 gene. and to detect very likely six distinct large deletions. Furthermore, we were able to confirm that there was no deletion in twenty one patients where no mutation had been found. Conclusion The identified mutations affect highly conserved amino acids, cause frameshifts or alternative splicing, thus affecting folding of the OA1 G protein coupled receptor, interactions of OA1 with its G protein and/or binding with its ligand. PMID:16646960

  13. Previous prelabor or intrapartum cesarean delivery and risk of placenta previa.

    PubMed

    Downes, Katheryne L; Hinkle, Stefanie N; Sjaarda, Lindsey A; Albert, Paul S; Grantz, Katherine L

    2015-05-01

    The purpose of this study was to examine the association between previous cesarean delivery and subsequent placenta previa while distinguishing cesarean delivery before the onset of labor from intrapartum cesarean delivery. We conducted a retrospective cohort study of electronic medical records from 20 Utah hospitals (2002-2010) with restriction to the first 2 singleton deliveries of nulliparous women at study entry (n=26,987). First pregnancy delivery mode was classified as (1) vaginal (reference), (2) cesarean delivery before labor onset (prelabor), or (3) cesarean delivery after labor onset (intrapartum). Risk of second delivery previa was estimated by previous delivery mode with the use of logistic regression and was adjusted for maternal age, insurance, smoking, comorbidities, previous pregnancy loss, and history of previa. Most first deliveries were vaginal (82%; n=22,142), followed by intrapartum cesarean delivery (14.6%; n=3931), or prelabor cesarean delivery (3.4%; n=914). Incidence of second delivery previa was 0.29% (n=78) and differed by previous delivery mode: vaginal, 0.24%; prelabor cesarean delivery, 0.98%; intrapartum cesarean delivery, 0.38% (P<.001). Relative to vaginal delivery, previous prelabor cesarean delivery was associated with an increased risk of second delivery previa (adjusted odds ratio, 2.62; 95% confidence interval, 1.24-5.56). There was no significant association between previous intrapartum cesarean delivery and previa (adjusted odds ratio, 1.22; 95% confidence interval, 0.68-2.19). Previous prelabor cesarean delivery was associated with a >2-fold significantly increased risk of previa in the second delivery, although the approximately 20% increased risk of previa that was associated with previous intrapartum cesarean delivery was not significant. Although rare, the increased risk of placenta previa after previous prelabor cesarean delivery may be important when considering nonmedically indicated prelabor cesarean delivery

  14. Willingness to Participate in Clinical Trials Among African Americans and Whites Previously Exposed To Clinical Research

    PubMed Central

    Durant, Raegan W.; Legedza, Anna T.; Marcantonio, Edward R.; Freeman, Marcie B.; Landon, Bruce E.

    2011-01-01

    The objective of this study was to identify racial differences in willingness to participate in a population with previous exposure to clinical research. A survey instrument was administered to community-dwelling whites and African Americans who were voluntarily receiving a lay research and health education newsletter from a local Boston geriatric clinical research institution. The survey instrument assessed willingness to participate in 3 hypothetical clinical trials (diet trial for obesity, medication trial for hypertension [HTN], chemotherapy trial for cancer). Surveys were received from 473 whites and 279 African Americans (53% response rate) with mean age 74 (SD ± 9). In multivariate models, race was not significantly related to willingness to participate in the multivariate models for any of the 3 trials. Previous trial participation was related to a higher odds of willingness to participate in the diet trial only (OR 1.8, 95% CI 1.2,2.6). Lower levels of trust in one’s primary care physician were associated with a lower odds of willingness to participate in clinical trials for the diet and HTN trials (OR 0.5, 95% CI 0.3,0.8 and OR 0.6, 95% CI 0.3,0.9, respectively). These findings suggest that, within populations previously exposed to clinical research, African Americans are no less willing to participate in clinical trials compared to whites. PMID:21526582

  15. An algorithm to identify functional groups in organic molecules.

    PubMed

    Ertl, Peter

    2017-06-07

    The concept of functional groups forms a basis of organic chemistry, medicinal chemistry, toxicity assessment, spectroscopy and also chemical nomenclature. All current software systems to identify functional groups are based on a predefined list of substructures. We are not aware of any program that can identify all functional groups in a molecule automatically. The algorithm presented in this article is an attempt to solve this scientific challenge. An algorithm to identify functional groups in a molecule based on iterative marching through its atoms is described. The procedure is illustrated by extracting functional groups from the bioactive portion of the ChEMBL database, resulting in identification of 3080 unique functional groups. A new algorithm to identify all functional groups in organic molecules is presented. The algorithm is relatively simple and full details with examples are provided, therefore implementation in any cheminformatics toolkit should be relatively easy. The new method allows the analysis of functional groups in large chemical databases in a way that was not possible using previous approaches. Graphical abstract .

  16. Activating cysteinyl leukotriene receptor 2 (CYSLTR2) mutations in blue nevi

    PubMed Central

    Möller, Inga; Murali, Rajmohan; Müller, Hansgeorg; Wiesner, Thomas; Jackett, Louise A; Scholz, Simone L; Cosgarea, Ioana; van de Nes, Johannes AP; Sucker, Antje; Hillen, Uwe; Schilling, Bastian; Paschen, Annette; Kutzner, Heinz; Rütten, Arno; Böckers, Martin; Scolyer, Richard A; Schadendorf, Dirk; Griewank, Klaus G

    2017-01-01

    Blue nevi are common melanocytic tumors arising in the dermal layer of the skin. Similar to uveal melanomas, blue nevi frequently harbor GNAQ and GNA11 mutations. Recently, recurrent CYSLTR2 and PLCB4 mutations were identified in uveal melanomas not harboring GNAQ or GNA11 mutations. All four genes (GNAQ, GNA11, CYSLTR2, and PLCB4) code for proteins involved in the same signaling pathway, which is activated by mutations in these genes. Given the related functional consequences of these mutations and the known genetic similarities between uveal melanoma and blue nevi, we analyzed a cohort of blue nevi to investigate whether CYSLTR2 and PLCB4 mutations occur in tumors lacking GNAQ or GNA11 mutations (as in uveal melanoma). A targeted next-generation sequencing assay covering known activating mutations in GNAQ, GNA11, CYSLTR2, PLCB4, KIT, NRAS, and BRAF was applied to 103 blue nevi. As previously reported, most blue nevi were found to harbor activating mutations in GNAQ (59%, n = 61), followed by less frequent mutations in GNA11 (16%, n = 17). Additionally, one BRAF (1%) and three NRAS (3%) mutations were detected. In three tumors (3%) harboring none of the aforementioned gene alterations, CYSLTR2 mutations were identified. All three CYSLTR2 mutations were the same c.386T > A, L129Q mutation previously identified in uveal melanoma that has been shown to lead to increased receptor activation and signaling. In summary, our study identifies CYSLTR2 L129Q alterations as a previously unrecognized activating mutation in blue nevi, occuring in a mutually exclusive fashion with known GNAQ and GNA11 mutations. Similar to GNAQ and GNA11 mutations, CYSLTR2 mutations, when present, are likely defining pathogenetic events in blue nevi. PMID:27934878

  17. Activating cysteinyl leukotriene receptor 2 (CYSLTR2) mutations in blue nevi.

    PubMed

    Möller, Inga; Murali, Rajmohan; Müller, Hansgeorg; Wiesner, Thomas; Jackett, Louise A; Scholz, Simone L; Cosgarea, Ioana; van de Nes, Johannes Ap; Sucker, Antje; Hillen, Uwe; Schilling, Bastian; Paschen, Annette; Kutzner, Heinz; Rütten, Arno; Böckers, Martin; Scolyer, Richard A; Schadendorf, Dirk; Griewank, Klaus G

    2017-03-01

    Blue nevi are common melanocytic tumors arising in the dermal layer of the skin. Similar to uveal melanomas, blue nevi frequently harbor GNAQ and GNA11 mutations. Recently, recurrent CYSLTR2 and PLCB4 mutations were identified in uveal melanomas not harboring GNAQ or GNA11 mutations. All four genes (GNAQ, GNA11, CYSLTR2, and PLCB4) code for proteins involved in the same signaling pathway, which is activated by mutations in these genes. Given the related functional consequences of these mutations and the known genetic similarities between uveal melanoma and blue nevi, we analyzed a cohort of blue nevi to investigate whether CYSLTR2 and PLCB4 mutations occur in tumors lacking GNAQ or GNA11 mutations (as in uveal melanoma). A targeted next-generation sequencing assay covering known activating mutations in GNAQ, GNA11, CYSLTR2, PLCB4, KIT, NRAS, and BRAF was applied to 103 blue nevi. As previously reported, most blue nevi were found to harbor activating mutations in GNAQ (59%, n=61), followed by less frequent mutations in GNA11 (16%, n=17). Additionally, one BRAF (1%) and three NRAS (3%) mutations were detected. In three tumors (3%) harboring none of the aforementioned gene alterations, CYSLTR2 mutations were identified. All three CYSLTR2 mutations were the same c.386T>A, L129Q mutation previously identified in uveal melanoma that has been shown to lead to increased receptor activation and signaling. In summary, our study identifies CYSLTR2 L129Q alterations as a previously unrecognized activating mutation in blue nevi, occuring in a mutually exclusive fashion with known GNAQ and GNA11 mutations. Similar to GNAQ and GNA11 mutations, CYSLTR2 mutations, when present, are likely defining pathogenetic events in blue nevi.

  18. Using passive sampling and zebrafish to identify developmental toxicants in complex mixtures.

    PubMed

    Bergmann, Alan J; Tanguay, Robert L; Anderson, Kim A

    2017-09-01

    Using effects-directed analysis, we investigated associations previously observed between polycyclic aromatic hydrocarbons (PAHs) and embryotoxicity in field-deployed low-density polyethylene (LDPE). We conducted effects-directed analysis using a zebrafish embryo assay and iterative fractionation of extracts of LDPE that were deployed in the Portland Harbor superfund megasite, Oregon (USA). Whole extracts induced toxicity including mortality, edema, and notochord distortion at 20% effect concentration (EC20) values of approximately 100, 100, and 10 mg LDPE/mL, respectively. Through fractionation, we determined that PAHs at concentrations similar to previous research did not contribute markedly to toxicity. We also eliminated pesticides, phthalates, musks, and other substances identified in toxic fractions by testing surrogate mixtures. We identified free fatty acids as lethal components of LDPE extracts and confirmed their toxicity with authentic standards. We found chromatographic evidence that dithiocarbamates are responsible for notochord and other sublethal effects, although exact matches were not obtained. Fatty acids and dithiocarbamates were previously unrecorded components of LDPE extracts and likely contribute to the toxicity of the whole mixture. The present study demonstrates the success of effects-directed analysis in nontargeted hazard identification using the zebrafish embryo test as a self-contained battery of bioassays that allows identification of multiple chemicals with different modes of action. This is the first effects-directed analysis to combine LDPE and zebrafish, approaches that are widely applicable to identifying developmental hazards in the bioavailable fraction of hydrophobic organic compounds. Environ Toxicol Chem 2017;36:2290-2298. © 2017 SETAC. © 2017 SETAC.

  19. Human Papilloma Virus Identification in Breast Cancer Patients with Previous Cervical Neoplasia.

    PubMed

    Lawson, James S; Glenn, Wendy K; Salyakina, Daria; Clay, Rosemary; Delprado, Warick; Cheerala, Bharathi; Tran, Dinh D; Ngan, Christopher C; Miyauchi, Shingo; Karim, Martha; Antonsson, Annika; Whitaker, Noel J

    2015-01-01

    Women with human papilloma virus (HPV)-associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i) identify high-risk HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii) determine if these HPVs were biologically active. A range of polymerase chain reaction and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. The same high-risk HPV types were identified in both the cervical and breast specimens in 13 (46%) of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV-associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001). These findings indicate that high-risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However, these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of two similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

  20. Lurking in the Shadows: Emerging Rodent Infectious Diseases

    PubMed Central

    Besselsen, David G.; Franklin, Craig L.; Livingston, Robert S.; Riley, Lela K.

    2013-01-01

    Rodent parvoviruses, Helicobacter spp., murine norovirus, and several other previously unknown infectious agents have “emerged” in laboratory rodents relatively recently. These agents have been discovered serendipitously or through active investigation of atypical serology results, cell culture contamination, unexpected histopathology, or previously unrecognized clinical disease syndromes. The potential research impact of these agents is not fully known. Infected rodents have demonstrated immunomodulation, tumor suppression, clinical disease (particularly in immunodeficient rodents), and histopathology. Perturbations of organismal and cellular physiology also likely occur. These agents posed unique challenges to laboratory animal resource programs once discovered; it was necessary to develop specific diagnostic assays and an understanding of their epidemiology and transmission routes before attempting eradication, and then evaluate eradication methods for efficacy. Even then management approaches varied significantly, from apathy to total exclusion, and such inconsistency has hindered the sharing and transfer of rodents among institutions, particularly for genetically modified rodent models that may not be readily available. As additional infectious agents are discovered in laboratory rodents in coming years, much of what researchers have learned from experiences with the recently identified pathogens will be applicable. This article provides an overview of the discovery, detection, and research impact of infectious agents recently identified in laboratory rodents. We also discuss emerging syndromes for which there is a suspected infectious etiology, and the unique challenges of managing newly emerging infectious agents. PMID:18506061

  1. Widespread occurrence of organelle genome-encoded 5S rRNAs including permuted molecules

    PubMed Central

    Valach, Matus; Burger, Gertraud; Gray, Michael W.; Lang, B. Franz

    2014-01-01

    5S Ribosomal RNA (5S rRNA) is a universal component of ribosomes, and the corresponding gene is easily identified in archaeal, bacterial and nuclear genome sequences. However, organelle gene homologs (rrn5) appear to be absent from most mitochondrial and several chloroplast genomes. Here, we re-examine the distribution of organelle rrn5 by building mitochondrion- and plastid-specific covariance models (CMs) with which we screened organelle genome sequences. We not only recover all organelle rrn5 genes annotated in GenBank records, but also identify more than 50 previously unrecognized homologs in mitochondrial genomes of various stramenopiles, red algae, cryptomonads, malawimonads and apusozoans, and surprisingly, in the apicoplast (highly derived plastid) genomes of the coccidian pathogens Toxoplasma gondii and Eimeria tenella. Comparative modeling of RNA secondary structure reveals that mitochondrial 5S rRNAs from brown algae adopt a permuted triskelion shape that has not been seen elsewhere. Expression of the newly predicted rrn5 genes is confirmed experimentally in 10 instances, based on our own and published RNA-Seq data. This study establishes that particularly mitochondrial 5S rRNA has a much broader taxonomic distribution and a much larger structural variability than previously thought. The newly developed CMs will be made available via the Rfam database and the MFannot organelle genome annotator. PMID:25429974

  2. HSP60 induces self-tolerance to repeated HSP60 stimulation and cross-tolerance to other pro-inflammatory stimuli.

    PubMed

    Kilmartin, Barry; Reen, Denis J

    2004-07-01

    In addition to their primary function as intracellular chaperone proteins, the immunomodulatory properties of heat shock proteins (HSP), including their role as adjuvants for vaccines, have become a focus of intense research interest. Interestingly, the effect of chronic exposure to an endogenous immunomodulator and initiator of inflammation such as autologous HSP60 has as yet remained uncharacterized. In this study, we demonstrate that pretreatment of monocytes with human HSP60 results in a suppression of TNF-alpha production on restimulation with HSP60. Furthermore, desensitization with HSP60 inhibits TNF-alpha expression in these cells in response to LPS stimulation, thereby inducing "cross-tolerance". In contrast to TNF-alpha suppression, IL-1beta expression was augmented in HSP60-pretreated monocytes on restimulation, while being suppressed in THP-1 cells. Addition of an anti-IL-10 neutralizing antibody had no significant effect on HSP60- or LPS-induced tolerance.HSP60 priming of monocytes also results in significant down-regulation of HLA-DR, CD86 and Toll-like receptor 4 expression, but minimally up-regulates CD80 expression, similar to that previously reported with LPS. By identifying a previously unrecognized "tolerizing" effect of extended exposure to autologous HSP60 on the innate immune system, as opposed to its recently identified pro-inflammatory stimulatory capacity, this study highlights a further level of complexity of our understanding of the biological activities of HSP.

  3. Wildlife Loss Estimates and Summary of Previous Mitigation Related to Hydroelectric Projects in Montana, Volume Three, Hungry Horse Project.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Casey, Daniel

    1984-10-01

    This assessment addresses the impacts to the wildlife populations and wildlife habitats due to the Hungry Horse Dam project on the South Fork of the Flathead River and previous mitigation of theses losses. In order to develop and focus mitigation efforts, it was first necessary to estimate wildlife and wildlife hatitat losses attributable to the construction and operation of the project. The purpose of this report was to document the best available information concerning the degree of impacts to target wildlife species. Indirect benefits to wildlife species not listed will be identified during the development of alternative mitigation measures. Wildlifemore » species incurring positive impacts attributable to the project were identified.« less

  4. IDENTIFYING PROBABLE DIABETES MELLITUS AMONG HISPANICS/LATINOS FROM FOUR U.S. CITIES: FINDINGS FROM THE HISPANIC COMMUNITY HEALTH STUDY/STUDY OF LATINOS.

    PubMed

    Avilés-Santa, M Larissa; Schneiderman, Neil; Savage, Peter J; Kaplan, Robert C; Teng, Yanping; Pérez, Cynthia M; Suárez, Erick L; Cai, Jianwen; Giachello, Aida L; Talavera, Gregory A; Cowie, Catherine C

    2016-10-01

    The aim of this study was to compare the ability of American Diabetes Association (ADA) diagnostic criteria to identify U.S. Hispanics/Latinos from diverse heritage groups with probable diabetes mellitus and assess cardiovascular risk factor correlates of those criteria. Cross-sectional analysis of data from 15,507 adults from 6 Hispanic/Latino heritage groups, enrolled in the Hispanic Community Health Study/Study of Latinos. The prevalence of probable diabetes mellitus was estimated using individual or combinations of ADA-defined cut points. The sensitivity and specificity of these criteria at identifying diabetes mellitus from ADA-defined prediabetes and normoglycemia were evaluated. Prevalence ratios of hypertension, abnormal lipids, and elevated urinary albumin-creatinine ratio for unrecognized diabetes mellitus-versus prediabetes and normoglycemia-were calculated. Among Hispanics/Latinos (mean age, 43 years) with diabetes mellitus, 39.4% met laboratory test criteria for probable diabetes, and the prevalence varied by heritage group. Using the oral glucose tolerance test as the gold standard, the sensitivity of fasting plasma glucose (FPG) and hemoglobin A1c-alone or in combination-was low (18, 23, and 33%, respectively) at identifying probable diabetes mellitus. Individuals who met any criterion for probable diabetes mellitus had significantly higher (P<.05) prevalence of most cardiovascular risk factors than those with normoglycemia or prediabetes, and this association was not modified by Hispanic/Latino heritage group. FPG and hemoglobin A1c are not sensitive (but are highly specific) at detecting probable diabetes mellitus among Hispanics/Latinos, independent of heritage group. Assessing cardiovascular risk factors at diagnosis might prompt multitarget interventions and reduce health complications in this young population. 2hPG = 2-hour post-glucose load plasma glucose ADA = American Diabetes Association BMI = body mass index CV = cardiovascular FPG

  5. Revisiting Teaching Archetypes: Identifying Dominant Shaping Influences on Student Teacher's Identities

    ERIC Educational Resources Information Center

    Sugrue, Ciaran

    2004-01-01

    The primary aim of this article is to identify and interrogate the lay theories of contemporary student teachers and to indicate and illustrate the manner in which these "theories" manifest both continuity and change when contrasted with teaching archetypes and previously articulated lay theories of student teachers in the setting. It is…

  6. Comparative analysis of Edwardsiella isolates from fish in the eastern United States identifies two distinct genetic taxa amongst organisms phenotypically classified as E. tarda

    USGS Publications Warehouse

    Griffin, Matt J.; Quiniou, Sylvie M.; Cody, Theresa; Tabuchi, Maki; Ware, Cynthia; Cipriano, Rocco C.; Mauel, Michael J.; Soto, Esteban

    2013-01-01

    Edwardsiella tarda, a Gram-negative member of the family Enterobacteriaceae, has been implicated in significant losses in aquaculture facilities worldwide. Here, we assessed the intra-specific variability of E. tarda isolates from 4 different fish species in the eastern United States. Repetitive sequence mediated PCR (rep-PCR) using 4 different primer sets (ERIC I & II, ERIC II, BOX, and GTG5) and multi-locus sequence analysis of 16S SSU rDNA, groEl, gyrA, gyrB, pho, pgi, pgm, and rpoA gene fragments identified two distinct genotypes of E. tarda (DNA group I; DNA group II). Isolates that fell into DNA group II demonstrated more similarity to E. ictaluri than DNA group I, which contained the reference E. tarda strain (ATCC #15947). Conventional PCR analysis using published E. tarda-specific primer sets yielded variable results, with several primer sets producing no observable amplification of target DNA from some isolates. Fluorometric determination of G + C content demonstrated 56.4% G + C content for DNA group I, 60.2% for DNA group II, and 58.4% for E. ictaluri. Surprisingly, these isolates were indistinguishable using conventional biochemical techniques, with all isolates demonstrating phenotypic characteristics consistent with E. tarda. Analysis using two commercial test kits identified multiple phenotypes, although no single metabolic characteristic could reliably discriminate between genetic groups. Additionally, anti-microbial susceptibility and fatty acid profiles did not demonstrate remarkable differences between groups. The significant genetic variation (<90% similarity at gyrA, gyrB, pho, phi and pgm; <40% similarity by rep-PCR) between these groups suggests organisms from DNA group II may represent an unrecognized, genetically distinct taxa of Edwardsiella that is phenotypically indistinguishable from E. tarda.

  7. Do children's previous dental experience and fear affect their perceived oral health-related quality of life (OHRQoL)?

    PubMed

    Merdad, Leena; El-Housseiny, Azza A

    2017-01-16

    Oral health-related quality of life (OHRQoL) has been used to describe the consequences of oral health conditions and treatments in children. A better understanding of OHRQoL and its relationship with dental fear and previous dental experience is necessary to improve children's oral health status. The aim of this study was to investigate the association of dental history and experience with dental fear and the OHRQoL of children aged 11 to 14 years. A cross-sectional study was conducted using a multi-stage stratified sample of 1,312 middle school children. Information regarding OHRQoL was collected from the children using the Child Perceptions Questionnaire (CPQ 11-14 ), and information regarding dental fear was collected using the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS). Information on past dental experiences and sociodemographic data were collected from the parents using self-administered questionnaires. Dental examinations were performed to assess caries experience. The multivariable model indicated that dental fear was the strongest predictor of OHRQoL as the fearful children had on average CPQ 11-14 scores that were 10 units higher than those of the non-fearful children. Regarding past dental experience, pain as the reason for the most recent dental visit was associated with poor OHRQoL, while receiving a filling during the previous dental visits was significantly associated with better OHRQoL. In addition, a larger number of siblings, a lower family income, a lower paternal education level, health problems and prior hospitalization were significantly associated with poor OHRQoL. This study identified that dental fear and some factors related to previous dental experience are associated with OHRQoL. In dental practice, children with dental fear should be identified, guided and treated early to avoid deterioration of their OHRQoL.

  8. Cultivation of a Synergistetes strain representing a previously uncultivated lineage

    PubMed Central

    Vartoukian, S R; Palmer, R M; Wade, W G

    2010-01-01

    Subgingival plaque samples obtained from human subjects with periodontitis, shown to include previously uncultivable members of the phylum Synergistetes, were used to inoculate Cooked Meat Medium (CMM). The presence of Cluster A (uncultivable) Synergistetes was monitored by fluorescent in situ hybridization (FISH) and quantitative PCR (Q-PCR). Cluster A Synergistetes were found to grow in CMM in co-culture with other plaque bacteria and growth was stimulated by the addition of mucin and serum. Plaque samples were also used to inoculate Blood Agar (BA) plates and growth of Cluster A Synergistetes was revealed after anaerobic incubation, by colony hybridization with specific probes. Surface growth on the plates in regions identified by colony hybridization was harvested and used to inoculate fresh plates, thus enriching for Cluster A Synergistetes. Cross-streaks of other plaque bacteria were also used to stimulate Synergistetes growth. In the early passages, no discrete Synergistetes colonies were seen, but after eight passages and the use of cross-streaks of other bacteria present in the enriched community, colonies arose, which consisted solely of Cluster A Synergistetes cells, as determined by 16S rRNA gene PCR and cloning. This is the first report of the successful culture of a member of the uncultivable branch of this phylum. PMID:20074237

  9. Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map.

    PubMed

    Hewett, Duncan; Samuelsson, Lena; Polding, Joanne; Enlund, Fredrik; Smart, Devi; Cantone, Kathryn; See, Chee Gee; Chadha, Sapna; Inerot, Annica; Enerback, Charlotta; Montgomery, Doug; Christodolou, Chris; Robinson, Phil; Matthews, Paul; Plumpton, Mary; Wahlstrom, Jan; Swanbeck, Gunnar; Martinsson, Tommy; Roses, Allen; Riley, John; Purvis, Ian

    2002-03-01

    Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.

  10. Antibody profiling using a recombinant protein-based multiplex ELISA array accelerates recombinant vaccine development: Case study on red sea bream iridovirus as a reverse vaccinology model.

    PubMed

    Matsuyama, Tomomasa; Sano, Natsumi; Takano, Tomokazu; Sakai, Takamitsu; Yasuike, Motoshige; Fujiwara, Atushi; Kawato, Yasuhiko; Kurita, Jun; Yoshida, Kazunori; Shimada, Yukinori; Nakayasu, Chihaya

    2018-05-03

    Predicting antigens that would be protective is crucial for the development of recombinant vaccine using genome based vaccine development, also known as reverse vaccinology. High-throughput antigen screening is effective for identifying vaccine target genes, particularly for pathogens for which minimal antigenicity data exist. Using red sea bream iridovirus (RSIV) as a research model, we developed enzyme-linked immune sorbent assay (ELISA) based RSIV-derived 72 recombinant antigen array to profile antiviral antibody responses in convalescent Japanese amberjack (Seriola quinqueradiata). Two and three genes for which the products were unrecognized and recognized, respectively, by antibodies in convalescent serum were selected for recombinant vaccine preparation, and the protective effect was examined in infection tests using Japanese amberjack and greater amberjack (S. dumerili). No protection was provided by vaccines prepared from gene products unrecognized by convalescent serum antibodies. By contrast, two vaccines prepared from gene products recognized by serum antibodies induced protective immunity in both fish species. These results indicate that ELISA array screening is effective for identifying antigens that induce protective immune responses. As this method does not require culturing of pathogens, it is also suitable for identifying protective antigens to un-culturable etiologic agents. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Epidemiology and healthcare costs of incident Clostridium difficile infections identified in the outpatient healthcare setting.

    PubMed

    Kuntz, Jennifer L; Johnson, Eric S; Raebel, Marsha A; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Spindel, Steven J; Neil, Nancy; Smith, David H

    2012-10-01

    To describe the epidemiology and healthcare costs of Clostridium difficile infection (CDI) identified in the outpatient setting. Population-based, retrospective cohort study. Kaiser Permanente Colorado and Kaiser Permanente Northwest members between June 1, 2005, and September 30, 2008. We identified persons with incident CDI and classified CDI by whether it was identified in the outpatient or inpatient healthcare setting. We collected information about baseline variables and follow-up healthcare utilization, costs, and outcomes among patients with CDI. We compared characteristics of patients with CDI identified in the outpatient versus inpatient setting. We identified 3,067 incident CDIs; 56% were identified in the outpatient setting. Few strong, independent predictors of diagnostic setting were identified, although a previous stay in a nonacute healthcare institution (odds ratio [OR], 1.45 [95% confidence interval (CI), 1.13-1.86]) was statistically associated with outpatient-identified CDI, as was age from 50 to 59 years (OR, 1.64 [95% CI, 1.18-2.29]), 60 to 69 years (OR, 1.37 [95% CI, 1.03-1.82]), and 70 to 79 years (OR, 1.36 [95% CI, 1.06-1.74]), when compared with persons aged 80-89 years. We found that more than one-half of incident CDIs in this population were identified in the outpatient setting. Patients with outpatient-identified CDI were younger with fewer comorbidities, although they frequently had previous exposure to healthcare. These data suggest that practitioners should be aware of CDI and obtain appropriate diagnostic testing on outpatients with CDI symptoms.

  12. Identifying transcription factor functions and targets by phenotypic activation

    PubMed Central

    Chua, Gordon; Morris, Quaid D.; Sopko, Richelle; Robinson, Mark D.; Ryan, Owen; Chan, Esther T.; Frey, Brendan J.; Andrews, Brenda J.; Boone, Charles; Hughes, Timothy R.

    2006-01-01

    Mapping transcriptional regulatory networks is difficult because many transcription factors (TFs) are activated only under specific conditions. We describe a generic strategy for identifying genes and pathways induced by individual TFs that does not require knowledge of their normal activation cues. Microarray analysis of 55 yeast TFs that caused a growth phenotype when overexpressed showed that the majority caused increased transcript levels of genes in specific physiological categories, suggesting a mechanism for growth inhibition. Induced genes typically included established targets and genes with consensus promoter motifs, if known, indicating that these data are useful for identifying potential new target genes and binding sites. We identified the sequence 5′-TCACGCAA as a binding sequence for Hms1p, a TF that positively regulates pseudohyphal growth and previously had no known motif. The general strategy outlined here presents a straightforward approach to discovery of TF activities and mapping targets that could be adapted to any organism with transgenic technology. PMID:16880382

  13. Gregory the Great's metaphor of the physician of the heart as a model for pastoral identity.

    PubMed

    McGrath-Merkle, Clare

    2011-06-01

    The identity of the Roman Catholic priesthood remains in serious crisis. Scholars have called for a return to traditional sources to find possible solutions, including the Early Church Fathers and the Hebrew Bible. Following Oden, this article further explores Pope Gregory the Great's The Book of Pastoral Rule and his ideals regarding pastoral identity. Of unique importance is his notion of the pastor as a "physician of the heart," unrecognized previously as central to his project.

  14. 14 CFR 121.406 - Credit for previous CRM/DRM training.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Credit for previous CRM/DRM training. 121... previous CRM/DRM training. (a) For flightcrew members, the Administrator may credit CRM training received before March 19, 1998 toward all or part of the initial ground CRM training required by § 121.419. (b...

  15. 14 CFR 121.406 - Credit for previous CRM/DRM training.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Credit for previous CRM/DRM training. 121... previous CRM/DRM training. (a) For flightcrew members, the Administrator may credit CRM training received before March 19, 1998 toward all or part of the initial ground CRM training required by § 121.419. (b...

  16. Clustering of self-organizing map identifies five distinct medulloblastoma subgroups.

    PubMed

    Cao, Changjun; Wang, Wei; Jiang, Pucha

    2016-01-01

    Medulloblastoma is one the most malignant paediatric brain tumours. Molecular subgrouping these medulloblastomas will not only help identify specific cohorts for certain treatment but also improve confidence in prognostic prediction. Currently, there is a consensus of the existences of four distinct subtypes of medulloblastoma. We proposed a novel bioinformatics method, clustering of self-organizing map, to determine the subgroups and their molecular diversity. Microarray expression profiles of 46 medulloblastoma samples were analysed and five clusters with distinct demographics, clinical outcome and transcriptional profiles were identified. The previously reported Wnt subgroup was identified as expected. Three other novel subgroups were proposed for later investigation. Our findings underscore the value of SOM clustering for discovering the medulloblastoma subgroups. When the suggested subdivision has been confirmed in large cohorts, this method should serve as a part of routine classification of clinical samples.

  17. Challenging previous conceptions of vegetarianism and eating disorders.

    PubMed

    Fisak, B; Peterson, R D; Tantleff-Dunn, S; Molnar, J M

    2006-12-01

    The purpose of this study was to replicate and expand upon previous research that has examined the potential association between vegetarianism and disordered eating. Limitations of previous research studies are addressed, including possible low reliability of measures of eating pathology within vegetarian samples, use of only a few dietary restraint measures, and a paucity of research examining potential differences in body image and food choice motives of vegetarians versus nonvegetarians. Two hundred and fifty-six college students completed a number of measures of eating pathology and body image, and a food choice motives questionnaire. Interestingly, no significant differences were found between vegetarians and nonvegetarians in measures of eating pathology or body image. However, significant differences in food choice motives were found. Implications for both researchers and clinicians are discussed.

  18. Risk of Suicide Attempt Associated with Previous Attempts in One’s Army Unit

    PubMed Central

    Ursano, Robert J.; Kessler, Ronald C.; Naifeh, James A.; Mash, Holly Herberman; Fullerton, Carol S.; Bliese, Paul D.; Zaslavsky, Alan M.; Ng, Tsz Hin Hinz; Aliaga, Pablo A.; Wynn, Gary H.; Dinh, Hieu M.; McCarroll, James E.; Sampson, Nancy A.; Kao, Tzu-Cheg; Schoenbaum, Michael; Heeringa, Steven G.; Stein, Murray B.

    2017-01-01

    Objective Soldiers’ mental health is adversely affected by the death and injury of other unit members, but it is not known if risk of suicide attempt is influenced by previous suicide attempts in one’s unit. Method Using administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS), we identified person-month records for all active duty Regular Army enlisted soldiers who attempted suicide from 2004–2009 (n=9,650) and an equal-probability sample of control person-months (n=153,528). Logistic regression analyses examined the number of past-year suicide attempts in one’s unit as a predictor of subsequent suicide attempt, controlling for socio-demographics, service-related characteristics, prior mental health diagnosis, and other unit variables, including suicide-, combat-, and accident-related unit deaths. We also examined whether the influence of previous unit suicide attempts varied by military occupational specialty (MOS) and unit size. Results In adjusted models, soldiers were more likely to attempt suicide if one or more suicide attempts occurred in their unit during the past year (OR=1.4–2.3; p<0.001), with odds increasing as the number of unit attempts increased. The odds of suicide attempt among soldiers in a unit with five or more past-year attempts was more than twice that of soldiers in a unit with no previous attempts (OR=2.3; 95% CI=2.1–2.6). The association of previous unit suicide attempts with subsequent risk was significant whether soldiers had a combat arms MOS or other MOS (OR=1.4–2.3; p<0.001). It was also significant regardless of unit size, with the highest risk for those in smaller units (1–40 soldiers) (OR=2.1–5.9; p<0.001). The population-attributable risk proportion for one or more unit suicide attempts in the past year indicated that if this risk could be reduced to no unit attempts, 18.2% of attempts would not occur. Conclusions Soldiers’ risk of suicide attempt increased as the

  19. Identifying duplicate content using statistically improbable phrases

    PubMed Central

    Errami, Mounir; Sun, Zhaohui; George, Angela C.; Long, Tara C.; Skinner, Michael A.; Wren, Jonathan D.; Garner, Harold R.

    2010-01-01

    Motivation: Document similarity metrics such as PubMed's ‘Find related articles’ feature, which have been primarily used to identify studies with similar topics, can now also be used to detect duplicated or potentially plagiarized papers within literature reference databases. However, the CPU-intensive nature of document comparison has limited MEDLINE text similarity studies to the comparison of abstracts, which constitute only a small fraction of a publication's total text. Extending searches to include text archived by online search engines would drastically increase comparison ability. For large-scale studies, submitting short phrases encased in direct quotes to search engines for exact matches would be optimal for both individual queries and programmatic interfaces. We have derived a method of analyzing statistically improbable phrases (SIPs) for assistance in identifying duplicate content. Results: When applied to MEDLINE citations, this method substantially improves upon previous algorithms in the detection of duplication citations, yielding a precision and recall of 78.9% (versus 50.3% for eTBLAST) and 99.6% (versus 99.8% for eTBLAST), respectively. Availability: Similar citations identified by this work are freely accessible in the Déjà vu database, under the SIP discovery method category at http://dejavu.vbi.vt.edu/dejavu/ Contact: merrami@collin.edu PMID:20472545

  20. Identifying wide, cold planets within 8pc

    NASA Astrophysics Data System (ADS)

    Deacon, Niall; Kraus, Adam; Crossfield, Ian

    2014-12-01

    Direct imaging exoplanet studies have recently unveiled a previously-unexpected population of massive planets (up to 15 M_Jup) in wide orbits (>100AU). Although most of these discoveries have been around younger stars and have been of similar temperatures to field brown dwarfs, one object (WD 0806-661B), is the coldest planet known outside our solar system. We propose a survey of all stars and brown dwarfs within 8pc to identify massive planetary companions in the 150-1500AU separation range. We will 1) Measure the fraction of wide planetary mass companions to stars in the Solar neighbourhood. 2) Identify all planets within 8 parsecs with masses above 8 Jupiter masses in our chosen projected separation range with lower mass limits for closer and younger stars. 3) Identify approximately 8 planets, four of which will have temperatures below 300K making them ideal targets to study water clouds in cold atmospheres with both JWST and the next generation of ground-based extremely large telescopes. Our survey will be the most complete survey for wide planets to-date and will provide both a measurement of the wide planet population and a legacy of cold, well constrained targets for future observatories.

  1. A KCNJ10 mutation previously identified in the Russell group of terriers also occurs in Smooth-Haired Fox Terriers with hereditary ataxia and in related breeds.

    PubMed

    Rohdin, Cecilia; Gilliam, Douglas; O'Leary, Caroline A; O'Brien, Dennis P; Coates, Joan R; Johnson, Gary S; Jäderlund, Karin Hultin

    2015-05-23

    Hereditary ataxias with similar phenotypes were reported in the Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell Terrier. However, segregation analyses showed differing inheritance modes in these breeds. Recently, molecular genetic studies on the Russell group of terriers found independent mutations in KCNJ10 and CAPN1, each associated with a specific clinical subtype of inherited ataxia. The aim of this study was to clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs of other related breeds harbor either of the same mutations. A sub goal was to update the results of KCNJ10 genotyping in Russell group terriers. Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers with a similar phenotype were all homozygous for the KCNJ10 mutation. The same mutation was also found in a heterozygous state in clinically unaffected Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers. A KCNJ10 mutation, previously associated with an autosomal recessive spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers segregates in at least three more breeds descended from British hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening the likelihood that this genetic defect is indeed the causative mutation for the disease known as "hereditary ataxia" in Fox Terriers and "spinocerebellar ataxia with myokymia, seizures or both" in the Russell group of terriers.

  2. The unrecognized burden of typhoid fever.

    PubMed

    Obaro, Stephen K; Iroh Tam, Pui-Ying; Mintz, Eric Daniel

    2017-03-01

    Typhoid fever (TF), caused by Salmonella enterica serovar Typhi, is the most common cause of enteric fever, responsible for an estimated 129,000 deaths and more than 11 million cases annually. Although several reviews have provided global and regional TF disease burden estimates, major gaps in our understanding of TF epidemiology remain. Areas covered: We provide an overview of the gaps in current estimates of TF disease burden and offer suggestions for addressing them, so that affected communities can receive the full potential of disease prevention offered by vaccination and water, sanitation, and hygiene interventions. Expert commentary: Current disease burden estimates for TF do not capture cases from certain host populations, nor those with atypical presentations of TF, which may lead to substantial underestimation of TF cases and deaths. These knowledge gaps pose major obstacles to the informed use of current and new generation typhoid vaccines.

  3. [Cutaneous melanoma associated with previous nevus].

    PubMed

    Gutiérrez, María P; Barengo, Mónica; Mainardi, Claudio; Garay, Iliana; Kurpis, María; Ruiz Lascano, Alejandro

    2009-01-01

    The malignant melanoma is a neoplasia originated from the melanocytes located in the skin and other locations. Even though there is not information regarding its incidence and prevalence in our country, its most important risk factors are known. The melanoma can originate de novo or from previous melanocytic lesions. The concept that a melanocytic nevus can serve as a precursor lesion is supported by clinical and histological evidence. An observational, retrospective and analytical study was carried out in the Hospital Privado de Córdoba. The objective was to determine which is the frequency of association of malignant melanomas that develop on previous nevus. A total of 134 melanomas were analyzed. In 32 cases (24%), the melanomas were histologically associated with nevus, in individuals with Breslow's depth bigger than 1 mm the percentage of association was 16.3% while in those exhibiting Breslow smaller than 1 mm the percentage of association was 38.1%. Having evaluated the melanomas in relation to the Breslow and Clark classification, we observed that the nevus associated melanoma group showed less Breslow thickness and low Clark levels, which, by statistical analysis were shown to be significant predictors of the probabilty of finding this association (p < 0.027). This study demonstrates that the tumor thickness by itself is an independent predictive factor of the association melanoma-nevus. However, the rest of the variables studied did not throw significant results from the statistical point of view. In conclusion, patients must be educated for the control of new pigmented injuries as well as for the modification of preexisting nevi.

  4. Suicidality and Intersectionality among Students Identifying as Nonheterosexual and with a Disability

    ERIC Educational Resources Information Center

    King, Matthew T.; Merrin, Gabriel J.; Espelage, Dorothy L.; Grant, Nickholas J.; Bub, Kristen L.

    2018-01-01

    Research about students with disabilities and students identifying as LGBQ (lesbian, gay, bisexual, or questioning) reveals that both populations report more suicidality and peer victimization and less school connectedness than do their peers. No study has previously examined the intersection of these identities with regard to peer victimization,…

  5. 48 CFR 22.1009-2 - Attempt to identify possible places of performance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... possible places of performance. 22.1009-2 Section 22.1009-2 Federal Acquisition Regulations System FEDERAL... Contract Act of 1965, as Amended 22.1009-2 Attempt to identify possible places of performance. The... might be performed. The following may indicate possible places of performance: (a) Locations of previous...

  6. 48 CFR 22.1009-2 - Attempt to identify possible places of performance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... possible places of performance. 22.1009-2 Section 22.1009-2 Federal Acquisition Regulations System FEDERAL... Contract Act of 1965, as Amended 22.1009-2 Attempt to identify possible places of performance. The... might be performed. The following may indicate possible places of performance: (a) Locations of previous...

  7. Identifying Multiple Levels of Discussion-Based Teaching Strategies for Constructing Scientific Models

    ERIC Educational Resources Information Center

    Williams, Grant; Clement, John

    2015-01-01

    This study sought to identify specific types of discussion-based strategies that two successful high school physics teachers using a model-based approach utilized in attempting to foster students' construction of explanatory models for scientific concepts. We found evidence that, in addition to previously documented dialogical strategies that…

  8. Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

    PubMed Central

    Williams, Winfred W.; Salem, Rany M.; McKnight, Amy Jayne; Sandholm, Niina; Forsblom, Carol; Taylor, Andrew; Guiducci, Candace; McAteer, Jarred B.; McKay, Gareth J.; Isakova, Tamara; Brennan, Eoin P.; Sadlier, Denise M.; Palmer, Cameron; Söderlund, Jenny; Fagerholm, Emma; Harjutsalo, Valma; Lithovius, Raija; Gordin, Daniel; Hietala, Kustaa; Kytö, Janne; Parkkonen, Maija; Rosengård-Bärlund, Milla; Thorn, Lena; Syreeni, Anna; Tolonen, Nina; Saraheimo, Markku; Wadén, Johan; Pitkäniemi, Janne; Sarti, Cinzia; Tuomilehto, Jaakko; Tryggvason, Karl; Österholm, Anne-May; He, Bing; Bain, Steve; Martin, Finian; Godson, Catherine; Hirschhorn, Joel N.; Maxwell, Alexander P.; Groop, Per-Henrik; Florez, Jose C.

    2012-01-01

    We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated. PMID:22721967

  9. Productivity and career paths of previous recipients of Society for Academic Emergency Medicine research grant awards.

    PubMed

    Young, Kelly D

    2008-06-01

    The objective was to assess productivity of previous recipients of Society for Academic Emergency Medicine (SAEM) grant awards. All previous recipients of SAEM Research Training Grants, Neuroscience Research Awards, Scholarly Sabbatical Awards, and Emergency Medical Services (EMS) Research Fellowship awards funded through 2004 were identified through SAEM's records and surveyed. Award categories assessed were those still offered by SAEM at the time of the survey and therefore excluded the Geriatric Research Award. The 2005-2006 SAEM Grants Committee developed a survey using previous publications assessing productivity of training grants and fellowship awards and refined it through consensus review and limited pilot testing. We assessed measures of academic productivity (numbers of publications and additional grants awarded), commitment to an academic career, satisfaction with the SAEM award, and basic demographic information. Overall response rate was 70%; usable data were returned by all seven Research Training Grant awardees, both Neuroscience awardees, four of five Scholarly Sabbatical awardees, and six of 14 EMS Research Fellowship awardees. Of those who gave demographic information, 78% (14/18) were male and 94% (16/17) were non-Hispanic white. All the respondents remained in academics, and 14 of 19 felt that they will definitely be in academics 5 years from the time of the survey. They have a median of 1.8 original research publications per year since the end of their grant period, and 74% (14/19) have received subsequent federal funding. All found the SAEM award to be helpful or very helpful to their careers. Previous recipients of the SAEM grant awards show evidence of academic productivity in the form of subsequent grant funding and research publications, and the majority remain committed to and satisfied with their academic research careers.

  10. The randomised controlled trial design: unrecognized opportunities for health sciences librarianship.

    PubMed

    Eldredge, Jonathan D

    2003-06-01

    to describe the essential components of the Randomised Controlled Trial (RCT) and its major variations; to describe less conventional applications of the RCT design found in the health sciences literature with potential relevance to health sciences librarianship; to discuss the limited number of RCTs within health sciences librarianship. narrative review supported to a limited extent with PubMed and Library Literature database searches consistent with specific search parameters. In addition, more systematic methods, including handsearching of specific journals, to identify health sciences librarianship RCTs. While many RCTs within the health sciences follow more conventional patterns, some RCTs assume certain unique features. Selected examples illustrate the adaptations of this experimental design to answering questions of possible relevance to health sciences librarians. The author offers several strategies for controlling bias in library and informatics applications of the RCT and acknowledges the potential of the electronic era in providing many opportunities to utilize the blinding aspects of RCTs. RCTs within health sciences librarianship inhabit a limited number of subject domains such as education. This limited scope offers both advantages and disadvantages for making Evidence-Based Librarianship (EBL) a reality. The RCT design offers the potential to answer far more EBL questions than have been addressed by the design to date. Librarians need only extend their horizons through use of the versatile RCT design into new subject domains to facilitate making EBL a reality.

  11. Central serous choroidopathy in the Hallermann-Streiff Syndrome.

    PubMed

    Blair, N P; Brockhurst, R J; Lee, W

    1981-08-01

    Central serous choroidopathy was observed in a young patient with the Hallermann-Streiff syndrome. Typical features of this syndrome include microphthalmos, proportionate dwarfism, dyscephaly with birdlike facies, dental abnormalities, and hypotrichosis. Exceptional aspects of this case include age of onset (11 years), high hyperopic refractive error (+ 13.00 sphere), and multiple recurrences caused by six separate documented leaks from the choroid. Fundus changes previously reported in the Hallermann-Streiff syndrome, interpreted as chorioretinal pigmentary changes, may have been secondary to previous undiagnosed central serous choroidopathy. Periodic ophthalmoscopy should be performed and may detect unrecognized episodes of central serous choroidopathy for which photocoagulation would be beneficial.

  12. Impact of Previous Pharmacy Work Experience on Pharmacy School Academic Performance

    PubMed Central

    Mar, Ellena; T-L Tang, Terrill; Sasaki-Hill, Debra; Kuperberg, James R.; Knapp, Katherine

    2010-01-01

    Objectives To determine whether students' previous pharmacy-related work experience was associated with their pharmacy school performance (academic and clinical). Methods The following measures of student academic performance were examined: pharmacy grade point average (GPA), scores on cumulative high-stakes examinations, and advanced pharmacy practice experience (APPE) grades. The quantity and type of pharmacy-related work experience each student performed prior to matriculation was solicited through a student survey instrument. Survey responses were correlated with academic measures, and demographic-based stratified analyses were conducted. Results No significant difference in academic or clinical performance between those students with prior pharmacy experience and those without was identified. Subanalyses by work setting, position type, and substantial pharmacy work experience did not reveal any association with student performance. A relationship was found, however, between age and work experience, ie, older students tended to have more work experience than younger students. Conclusions Prior pharmacy work experience did not affect students' overall academic or clinical performance in pharmacy school. The lack of significant findings may have been due to the inherent practice limitations of nonpharmacist positions, changes in pharmacy education, and the limitations of survey responses. PMID:20498735

  13. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

    PubMed

    Lotta, Luca A; Gulati, Pawan; Day, Felix R; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J; Eicher, John D; Sharp, Stephen J; Luan, Jian'an; De Lucia Rolfe, Emanuella; Stewart, Isobel D; Wheeler, Eleanor; Willems, Sara M; Adams, Claire; Yaghootkar, Hanieh; Forouhi, Nita G; Khaw, Kay-Tee; Johnson, Andrew D; Semple, Robert K; Frayling, Timothy; Perry, John R B; Dermitzakis, Emmanouil; McCarthy, Mark I; Barroso, Inês; Wareham, Nicholas J; Savage, David B; Langenberg, Claudia; O'Rahilly, Stephen; Scott, Robert A

    2017-01-01

    Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

  14. High-resolution Myogenic Lineage Mapping by Single-Cell Mass Cytometry

    PubMed Central

    Porpiglia, Ermelinda; Samusik, Nikolay; Ho, Andrew Tri Van; Cosgrove, Benjamin D.; Mai, Thach; Davis, Kara L.; Jager, Astraea; Nolan, Garry P.; Bendall, Sean C.; Fantl, Wendy J.; Blau, Helen M.

    2017-01-01

    Muscle regeneration is a dynamic process during which cell state and identity change over time. A major roadblock has been a lack of tools to resolve a myogenic progression in vivo. Here we capitalize on a transformative technology, single-cell mass cytometry (CyTOF), to identify in vivo skeletal muscle stem cell and previously unrecognized progenitor populations that precede differentiation. We discovered two cell surface markers, CD9 and CD104, whose combined expression enabled in vivo identification and prospective isolation of stem and progenitor cells. Data analysis using the X-shift algorithm paired with single-cell force directed layout visualization, defined a molecular signature of the activated stem cell state (CD44+/CD98+/MyoD+) and delineated a myogenic trajectory during recovery from acute muscle injury. Our studies uncover the dynamics of skeletal muscle regeneration in vivo and pave the way for the elucidation of the regulatory networks that underlie cell-state transitions in muscle diseases and aging. PMID:28414312

  15. Integrated metatranscriptomics and metaproteomics for the characterization of bacterial microbiota in unfed Ixodes ricinus.

    PubMed

    Hernández-Jarguín, Angélica; Díaz-Sánchez, Sandra; Villar, Margarita; de la Fuente, José

    2018-05-05

    An innovative metaomics approach integrating metatranscriptomics and metaproteomics was used to characterize bacterial communities in the microbiota of the Lyme borreliosis spirochete vector, Ixodes ricinus (Acari: Ixodidae). Whole internal tissues and salivary glands from unfed larvae and female ticks, respectively were used. Reused I. ricinus RNA-sequencing data for metranscriptomics analysis together with metaproteomics provided a better characterization of tick bacterial microbiota by increasing bacteria identification and support for identified bacteria with putative functional implications. The results showed the presence of symbiotic, commensal, soil, environmental, and pathogenic bacteria in the I. ricinus microbiota, including previously unrecognized commensal and soil microorganisms. The results of the metaomics approach may have implications in the characterization of putative mechanisms by which pathogen infection manipulates tick microbiota to facilitate infection. Metaomics approaches integrating different omics datasets would provide a better description of tick microbiota compositions, and insights into tick interactions with microbiota, pathogens and hosts. Copyright © 2018 Elsevier GmbH. All rights reserved.

  16. The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii.

    PubMed

    Beiting, Daniel P; Hidano, Shinya; Baggs, Julie E; Geskes, Jeanne M; Fang, Qun; Wherry, E John; Hunter, Christopher A; Roos, David S; Cherry, Sara

    2015-07-01

    The protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses interferon gamma (IFN-γ)-induced signal transducer and activator of transcription 1 (STAT1) activity. We exploited this well-defined host-pathogen interaction as the basis for a high-throughput screen, identifying nine transcription factors that enhance STAT1 function in the nucleus, including the orphan nuclear hormone receptor TLX. Expression profiling revealed that upon IFN-γ treatment TLX enhances the output of a subset of IFN-γ target genes, which we found is dependent on TLX binding at those loci. Moreover, infection of TLX deficient mice with the intracellular parasite Toxoplasma results in impaired production of the STAT1-dependent cytokine interleukin-12 by dendritic cells and increased parasite burden in the brain during chronic infection. These results demonstrate a previously unrecognized role for this orphan nuclear hormone receptor in regulating STAT1 signaling and host defense and reveal that STAT1 activity can be modulated in a context-specific manner by such "modifiers."

  17. Reactive oxygen-mediated damage to a human DNA replication and repair protein.

    PubMed

    Montaner, Beatriz; O'Donovan, Peter; Reelfs, Olivier; Perrett, Conal M; Zhang, Xiaohong; Xu, Yao-Zhong; Ren, Xiaolin; Macpherson, Peter; Frith, David; Karran, Peter

    2007-11-01

    Ultraviolet A (UVA) makes up more than 90% of incident terrestrial ultraviolet radiation. Unlike shorter wavelength UVB, which damages DNA directly, UVA is absorbed poorly by DNA and is therefore considered to be less hazardous. Organ transplant patients treated with the immunosuppressant azathioprine frequently develop skin cancer. Their DNA contains 6-thioguanine-a base analogue that generates DNA-damaging singlet oxygen ((1)O(2)) when exposed to UVA. Here, we show that this (1)O(2) damages proliferating cell nuclear antigen (PCNA), the homotrimeric DNA polymerase sliding clamp. It causes covalent oxidative crosslinking between the PCNA subunits through a histidine residue in the intersubunit domain. Crosslinking also occurs after treatment with higher-although still moderate-doses of UVA alone or with chemical oxidants. Chronic accumulation of oxidized proteins is linked to neurodegenerative disorders and ageing. Our findings identify oxidative damage to an important DNA replication and repair protein as a previously unrecognized hazard of acute oxidative stress.

  18. Naringenin is a novel inhibitor of Dictyostelium cell proliferation and cell migration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Russ, Misty; Martinez, Raquel; Ali, Hind

    2006-06-23

    Naringenin is a flavanone compound that alters critical cellular processes such as cell multiplication, glucose uptake, and mitochondrial activity. In this study, we used the social amoeba, Dictyostelium discoideum, as a model system for examining the cellular processes and signaling pathways affected by naringenin. We found that naringenin inhibited Dictyostelium cell division in a dose-dependent manner (IC{sub 5} {approx} 20 {mu}M). Assays of Dictyostelium chemotaxis and multicellular development revealed that naringenin possesses a previously unrecognized ability to suppress amoeboid cell motility. We also found that naringenin, which is known to inhibit phosphatidylinositol 3-kinase activity, had no apparent effect on phosphatidylinositolmore » 3,4,5-trisphosphate synthesis in live Dictyostelium cells; suggesting that this compound suppresses cell growth and migration via alternative signaling pathways. In another context, the discoveries described here highlight the value of using the Dictyostelium model system for identifying and characterizing the mechanisms by which naringenin, and related compounds, exert their effects on eukaryotic cells.« less

  19. Development of a plastic surgical teaching service in a women's correctional institution.

    PubMed

    Fisher, J C; Powers, W E; Tuerk, D B; Edgerton, M T

    1975-03-01

    A plastic surgical teaching service has been organized at a women's correctional institution to provide a previously unrecognized medical need and to serve a valuable educational function for our residents in training. A total of 177 surgical candidates demonstrating a wide range of reconstructive problems including tattoos, scars, keloids, neoplasms of the skin and hands, deformities of the face and breasts, and numerous disabilities of the hands were identified among 241 inmates requesting examination. Thus far, 116 operative procedures have been performed on 101 patients. Patient acceptance has been high, and the support of prison authorities has been enthusiastic. Persistent efforts to convince legislators of the wisdom of supporting this program financially have only been partially successful and will require further accumulation of sociologic data bearing on the rehabilitative potential of the detained patient with a correctable deformity. Meanwhile, residents in training gain maturity as they provide a very "private" type of service for what has traditionally been considered a very "public" population of patients.

  20. Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state

    PubMed Central

    Verfaillie, Annelien; Imrichova, Hana; Atak, Zeynep Kalender; Dewaele, Michael; Rambow, Florian; Hulselmans, Gert; Christiaens, Valerie; Svetlichnyy, Dmitry; Luciani, Flavie; Van den Mooter, Laura; Claerhout, Sofie; Fiers, Mark; Journe, Fabrice; Ghanem, Ghanem-Elias; Herrmann, Carl; Halder, Georg; Marine, Jean-Christophe; Aerts, Stein

    2015-01-01

    Transcriptional reprogramming of proliferative melanoma cells into a phenotypically distinct invasive cell subpopulation is a critical event at the origin of metastatic spreading. Here we generate transcriptome, open chromatin and histone modification maps of melanoma cultures; and integrate this data with existing transcriptome and DNA methylation profiles from tumour biopsies to gain insight into the mechanisms underlying this key reprogramming event. This shows thousands of genomic regulatory regions underlying the proliferative and invasive states, identifying SOX10/MITF and AP-1/TEAD as regulators, respectively. Knockdown of TEADs shows a previously unrecognized role in the invasive gene network and establishes a causative link between these transcription factors, cell invasion and sensitivity to MAPK inhibitors. Using regulatory landscapes and in silico analysis, we show that transcriptional reprogramming underlies the distinct cellular states present in melanoma. Furthermore, it reveals an essential role for the TEADs, linking it to clinically relevant mechanisms such as invasion and resistance. PMID:25865119