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Sample records for low-risk variants fgfr2

  1. A variant of fibroblast growth factor receptor 2 (Fgfr2 regulates left-right asymmetry in zebrafish.

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    Da-Wei Liu

    Full Text Available Many organs in vertebrates are left-right asymmetrical located. For example, liver is at the right side and stomach is at the left side in human. Fibroblast growth factor (Fgf signaling is important for left-right asymmetry. To investigate the roles of Fgfr2 signaling in zebrafish left-right asymmetry, we used splicing blocking morpholinos to specifically block the splicing of fgfr2b and fgfr2c variants, respectively. We found that the relative position of the liver and the pancreas were disrupted in fgfr2c morphants. Furthermore, the left-right asymmetry of the heart became random. Expression pattern of the laterality controlling genes, spaw and pitx2c, also became random in the morphants. Furthermore, lefty1 was not expressed in the posterior notochord, indicating that the molecular midline barrier had been disrupted. It was also not expressed in the brain diencephalon. Kupffer's vesicle (KV size became smaller in fgfr2c morphants. Furthermore, KV cilia were shorter in fgfr2c morphants. We conclude that the fgfr2c isoform plays an important role in the left-right asymmetry during zebrafish development.

  2. A variant of fibroblast growth factor receptor 2 (Fgfr2) regulates left-right asymmetry in zebrafish.

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    Liu, Da-Wei; Hsu, Chia-Hao; Tsai, Su-Mei; Hsiao, Chung-Der; Wang, Wen-Pin

    2011-01-01

    Many organs in vertebrates are left-right asymmetrical located. For example, liver is at the right side and stomach is at the left side in human. Fibroblast growth factor (Fgf) signaling is important for left-right asymmetry. To investigate the roles of Fgfr2 signaling in zebrafish left-right asymmetry, we used splicing blocking morpholinos to specifically block the splicing of fgfr2b and fgfr2c variants, respectively. We found that the relative position of the liver and the pancreas were disrupted in fgfr2c morphants. Furthermore, the left-right asymmetry of the heart became random. Expression pattern of the laterality controlling genes, spaw and pitx2c, also became random in the morphants. Furthermore, lefty1 was not expressed in the posterior notochord, indicating that the molecular midline barrier had been disrupted. It was also not expressed in the brain diencephalon. Kupffer's vesicle (KV) size became smaller in fgfr2c morphants. Furthermore, KV cilia were shorter in fgfr2c morphants. We conclude that the fgfr2c isoform plays an important role in the left-right asymmetry during zebrafish development.

  3. Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study

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    Nan, Hongmei; Qureshi, Abrar A; Hunter, David J; Han, Jiali

    2009-01-01

    The human fibroblast growth factor (FGF) and its receptor (FGFR) play an important role in tumorigenesis. Deregulation of the FGFR2 gene has been identified in a number of cancer sites. Overexpression of the FGFR4 protein has been linked to cutaneous melanoma progression. Previous studies reported associations between genetic variants in the FGFR2 and FGFR4 genes and development of various cancers. We evaluated the associations of four genetic variants in the FGFR2 gene highly related to breast cancer risk and the three common tag-SNPs in the FGFR4 gene with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 controls. We found no evidence for associations between these seven genetic variants and the risks of melanoma and nonmelanocytic skin cancer. Given the power of this study, we did not detect any contribution of genetic variants in the FGFR2 or FGFR4 genes to inherited predisposition to skin cancer among Caucasian women

  4. Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women

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    Huiying Liang

    2015-01-01

    Full Text Available GWAS have identified variation in the FGFR2 locus as risk factors for breast cancer. Validation studies, however, have shown inconsistent results by ethnics and pathological characteristics. To further explore this inconsistency and investigate the associations of FGFR2 variants with breast cancer according to intrinsic subtype (Luminal-A, Luminal-B, ER−&PR−&HER2+, and triple negative among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582 polymorphisms in 609 patients and 882 controls. Significant associations with breast cancer risk were observed for rs2420946, rs2981579, and rs2981582 with OR (95% CI per risk allele of 1.19 (1.03–1.39, 1.24 (1.07–1.43, and 1.17 (1.01–1.36, respectively. In subtype specific analysis, above three SNPs were significantly associated with increased Luminal-A risk in a dose-dependent manner Ptrend<0.01; however, only rs2981579 was associated with Luminal-B, and none were linked to ER−&PR− subtypes (ER−&PR−&HER2+ and triple negative. Haplotype analyses also identified common haplotypes significantly associated with luminal-like subtypes (Luminal-A and Luminal-B, but not with ER−&PR− subtypes. Our results suggest that associations of FGFR2 SNPs with breast cancer were heterogeneous according to intrinsic subtype. Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms underlying breast cancer.

  5. A study on genetic variants of Fibroblast growth factor receptor 2 (FGFR2 and the risk of breast cancer from North India.

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    Sarah Siddiqui

    Full Text Available Genome-Wide Association Studies (GWAS have identified Fibroblast growth factor receptor 2 (FGFR2 as a candidate gene for breast cancer with single nucleotide polymorphisms (SNPs located in intron 2 region as the susceptibility loci strongly associated with the risk. However, replicate studies have often failed to extrapolate the association to diverse ethnic regions. This hints towards the existing heterogeneity among different populations, arising due to differential linkage disequilibrium (LD structures and frequencies of SNPs within the associated regions of the genome. It is therefore important to revisit the previously linked candidates in varied population groups to unravel the extent of heterogeneity. In an attempt to investigate the role of FGFR2 polymorphisms in susceptibility to the risk of breast cancer among North Indian women, we genotyped rs2981582, rs1219648, rs2981578 and rs7895676 polymorphisms in 368 breast cancer patients and 484 healthy controls by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP assay. We observed a statistically significant association with breast cancer risk for all the four genetic variants (P<0.05. In per-allele model for rs2981582, rs1219648, rs7895676 and in dominant model for rs2981578, association remained significant after bonferroni correction (P<0.0125. On performing stratified analysis, significant correlations with various clinicopathological as well as environmental and lifestyle characteristics were observed. It was evident that rs1219648 and rs2981578 interacted with exogenous hormone use and advanced clinical stage III (after Bonferroni correction, P<0.000694, respectively. Furthermore, combined analysis on these four loci revealed that compared to women with 0-1 risk loci, those with 2-4 risk loci had increased risk (OR = 1.645, 95%CI = 1.152-2.347, P = 0.006. In haplotype analysis, for rs2981578, rs2981582 and rs1219648, risk haplotype (GTG was

  6. Identification of Functional Variants for Cleft Lip with or without Cleft Palate in or near PAX7, FGFR2, and NOG by Targeted Sequencing of GWAS Loci

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    Leslie, Elizabeth J; Taub, Margaret A; Liu, Huan

    2015-01-01

    Although genome-wide association studies (GWASs) for nonsyndromic orofacial clefts have identified multiple strongly associated regions, the causal variants are unknown. To address this, we selected 13 regions from GWASs and other studies, performed targeted sequencing in 1,409 Asian and European...

  7. FGFR2c-mediated ERK-MAPK activity regulates coronal suture development

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    Pfaff, Miles J.; Xue, Ke; Li, Li; Horowitz, Mark C.; Steinbacher, Derek M.; Eswarakumar, Jacob V.P.

    2017-01-01

    Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper craniofacial development. A gain-of-function mutation in the 2c splice variant of the receptor’s gene is associated with Crouzon syndrome, which is characterized by craniosynostosis, the premature fusion of one or more of the cranial vault sutures, leading to craniofacial maldevelopment. Insight into the molecular mechanism of craniosynostosis has identified the ERK-MAPK signaling cascade as a critical regulator of suture patency. The aim of this study is to investigate the role of FGFR2c-induced ERK-MAPK activation in the regulation of coronal suture development. Loss-of-function and gain-of-function Fgfr2c mutant mice have overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia. In vivo analysis of coronal sutures in loss-of-function and gain-of-function models demonstrated fundamentally different pathogenesis underlying coronal suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated enhanced osteoblastic function and maturation with concomitant increase in ERK-MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126 mitigated ERK protein activation levels with a concomitant reduction in alkaline phosphatase activity. This study identifies FGFR2c-mediated ERK-MAPK signaling as a key mediator of craniofacial growth and coronal suture development. Furthermore, our results solve the apparent paradox between loss-of-function and gain-of-function FGFR2c mutants with respect to coronal suture synostosis. PMID:27034231

  8. A de novo missense mutation of FGFR2 causes facial dysplasia syndrome in Holstein cattle

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    Agerholm, Jørgen Steen; McEvoy, Fintan; Heegaard, Steffen

    2017-01-01

    was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause. Results Seven malformed calves were submitted examination. All cases shared a common morphology with the most striking lesions being severe facial...... chromosome 26 where whole genome sequencing of a case-parent trio revealed two de novo variants perfectly associated with the disease: an intronic SNP in the DMBT1 gene and a single non-synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T) affects a gene encoding a member...... of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and across species. It is predicted to change an evolutionary conserved tryptophan into a cysteine residue (p.Trp309Cys). Both variant alleles were proven to result from de novo mutation events...

  9. A de novo missense mutation of FGFR2 causes facial dysplasia syndrome in Holstein cattle.

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    Agerholm, Jørgen S; McEvoy, Fintan J; Heegaard, Steffen; Charlier, Carole; Jagannathan, Vidhya; Drögemüller, Cord

    2017-08-02

    Surveillance for bovine genetic diseases in Denmark identified a hitherto unreported congenital syndrome occurring among progeny of a Holstein sire used for artificial breeding. A genetic aetiology due to a dominant inheritance with incomplete penetrance or a mosaic germline mutation was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause. Seven malformed calves were submitted examination. All cases shared a common morphology with the most striking lesions being severe facial dysplasia and complete prolapse of the eyes. Consequently the syndrome was named facial dysplasia syndrome (FDS). Furthermore, extensive brain malformations, including microencephaly, hydrocephalus, lobation of the cerebral hemispheres and compression of the brain were present. Subsequent data analysis of progeny of the sire revealed that around 0.5% of his offspring suffered from FDS. High density single nucleotide polymorphism (SNP) genotyping data of the seven cases and their parents were used to map the defect in the bovine genome. Significant genetic linkage was obtained for three regions, including chromosome 26 where whole genome sequencing of a case-parent trio revealed two de novo variants perfectly associated with the disease: an intronic SNP in the DMBT1 gene and a single non-synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T) affects a gene encoding a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and across species. It is predicted to change an evolutionary conserved tryptophan into a cysteine residue (p.Trp309Cys). Both variant alleles were proven to result from de novo mutation events in the germline of the sire. FDS is a novel genetic disorder of Holstein cattle. Mutations in the human FGFR2 gene are associated with various dominant inherited craniofacial dysostosis syndromes. Given

  10. FGFR2 promotes breast tumorigenicity through maintenance of breast tumor-initiating cells.

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    Sungeun Kim

    Full Text Available Emerging evidence suggests that some cancers contain a population of stem-like TICs (tumor-initiating cells and eliminating TICs may offer a new strategy to develop successful anti-cancer therapies. As molecular mechanisms underlying the maintenance of the TIC pool are poorly understood, the development of TIC-specific therapeutics remains a major challenge. We first identified and characterized TICs and non-TICs isolated from a mouse breast cancer model. TICs displayed increased tumorigenic potential, self-renewal, heterogeneous differentiation, and bipotency. Gene expression analysis and immunostaining of TICs and non-TICs revealed that FGFR2 was preferentially expressed in TICs. Loss of FGFR2 impaired self-renewal of TICs, thus resulting in marked decreases in the TIC population and tumorigenic potential. Restoration of FGFR2 rescued the defects in TIC pool maintenance, bipotency, and breast tumor growth driven by FGFR2 knockdown. In addition, pharmacological inhibition of FGFR2 kinase activity led to a decrease in the TIC population which resulted in suppression of breast tumor growth. Moreover, human breast TICs isolated from patient tumor samples were found enriched in a FGFR2+ population that was sufficient to initiate tumor growth. Our data suggest that FGFR2 is essential in sustaining the breast TIC pool through promotion of self-renewal and maintenance of bipotent TICs, and raise the possibility of FGFR2 inhibition as a strategy for anti-cancer therapy by eradicating breast TICs.

  11. Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure

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    Azuma, Koichi; Tsurutani, Junji; Sakai, Kazuko; Kaneda, Hiroyasu; Fujisaka, Yasuhito; Takeda, Masayuki; Watatani, Masahiro; Arao, Tokuzo; Satoh, Taroh; Okamoto, Isamu; Kurata, Takayasu; Nishio, Kazuto; Nakagawa, Kazuhiko

    2011-01-01

    Highlights: → A lapatinib-resistant breast cancer cell line, UACC812 (UACC812/LR), was found to harbor amplification of the FGFR2 gene. → Inhibition of the molecule by a specific inhibitor of FGFR dramatically induced growth inhibition accompanied by cell death. → Immunohistochemical analysis of patients with HER2-positive breast cancer demonstrated an association between FGFR2 expression and poor outcome for lapatinib-containing chemotherapy. -- Abstract: Agents that target HER2 have improved the prognosis of patients with HER2-amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC 50 of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2-targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2-positive breast cancer.

  12. Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure

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    Azuma, Koichi [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Tsurutani, Junji, E-mail: tsurutani_j@dotd.med.kindai.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Sakai, Kazuko; Kaneda, Hiroyasu [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Fujisaka, Yasuhito; Takeda, Masayuki [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Watatani, Masahiro [Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Arao, Tokuzo [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Satoh, Taroh; Okamoto, Isamu; Kurata, Takayasu [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan)

    2011-04-01

    Highlights: {yields} A lapatinib-resistant breast cancer cell line, UACC812 (UACC812/LR), was found to harbor amplification of the FGFR2 gene. {yields} Inhibition of the molecule by a specific inhibitor of FGFR dramatically induced growth inhibition accompanied by cell death. {yields} Immunohistochemical analysis of patients with HER2-positive breast cancer demonstrated an association between FGFR2 expression and poor outcome for lapatinib-containing chemotherapy. -- Abstract: Agents that target HER2 have improved the prognosis of patients with HER2-amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC{sub 50} of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2-targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2-positive breast cancer.

  13. FGFR2 amplification is predictive of sensitivity to regorafenib in gastric and colorectal cancers in vitro.

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    Cha, Yongjun; Kim, Hwang-Phill; Lim, Yoojoo; Han, Sae-Won; Song, Sang-Hyun; Kim, Tae-You

    2018-03-24

    Although regorafenib has demonstrated survival benefits in patients with metastatic colorectal and gastrointestinal stromal tumors, no proven biomarker has been identified for predicting sensitivity to regorafenib. Here, we investigated preclinical activity of regorafenib in gastric and colorectal cancer cells to identify genetic alterations associated with sensitivity to regorafenib. Mutation profiles and copy number assays of regorafenib target molecules indicated that amplification of FGFR2 was the only genetic alteration associated with in vitro sensitivity to regorafenib. Regorafenib effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules in a dose-dependent manner and selectively in FGFR2 amplified cells. Regorafenib induced G1 arrest (SNU-16, KATO-III) and apoptosis (NCI-H716), however, no significant changes were seen in cell lines without FGFR2 amplification. In SNU-16 mice xenografts, regorafenib significantly inhibited tumor growth, proliferation, and FGFR signaling compared to treatment with control vehicle. Regorafenib effectively abrogates activated FGFR2 signaling in FGFR2 amplified gastric and colorectal cancer and therefore, might be considered for integration into treatment in patients with FGFR2 amplified gastric and colorectal cancers. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  14. Changes in FGFR2 amino-acid residue Asn549 lead to Crouzon and Pfeiffer syndrome with hydrocephalus

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    Caroline Apra

    2016-10-01

    Full Text Available Mutations in Fibroblast Growth Factor Receptor II (FGFR2 have been identified in patients with Crouzon and Pfeiffer syndrome, among which rare mutations of the intracellular tyrosine kinase domain. Correlating subtle phenotypes with each rare mutation is still in progress. In Necker-Enfants Malades Hospital, we identified three patients harboring three different pathogenic variants of the same amino acid residue Asn-549 located in this domain: in addition to a very typical crouzonoid appearance, they all developed clinically relevant hydrocephalus, which is an inconstant feature of Crouzon and Pfeiffer syndrome. Overall, FGFR2 tyrosine kinase domain mutations account for 5/67 (7.4% cases in our hospital. We describe a novel mutation, p.Asn549Ser, and new cases of p.Asn549His and p.Asn549Thr mutations, each reported once before. Our three cases of Asn-549 mutations, alongside with rare previously reported cases, show that these patients are at higher risk of hydrocephalus. Clinical and imaging follow-up, with possible early surgery, may help prevent secondary intellectual disability.

  15. FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells

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    Lukasz Turczyk

    2017-10-01

    Full Text Available Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa. Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.

  16. Novel mutation detection of fibroblast growth factor receptor 1 (FGFR1) gene, FGFR2IIIa, FGFR2IIIb, FGFR2IIIc, FGFR3, FGFR4 gene for craniosynostosis: A prospective study in Asian Indian patient.

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    Barik, Mayadhar; Bajpai, Minu; Malhotra, Arun; Samantaray, Jyotish Chandra; Dwivedi, Sadananda; Das, Sambhunath

    2015-01-01

    Craniosynostosis (CS) syndrome is an autosomal dominant condition classically combining craniosynostosis and non-syndromic craniosynostosis with digital anomalies of the hands and feet. The majority of cases are caused by heterozygous mutations in the third immunoglobulin-like domain (IgIII) of FGFR2, whilst a larger number of cases can be attributed to mutations outside this region of the protein. To find out the FGFR1, FGFR2, FGFR3 and FGFR4 gene in craniosynostosis syndrome. A hospital based prospective study. Prospective analysis of clinical records of patients registered in CS clinic from December 2007 to January 2015 was done in patients between 4 months to 13 years of age. We have performed genetic findings in a three generation Indian family with Craniosynostosis syndrome. We report for the first time the clinical and genetic findings in a three generation Indian family with Craniosynostosis syndrome caused by a heterozygous missense mutation, Thr 392 Thr and ser 311 try, located in the IgII domain of FGFR2. FGFR 3 and 4 gene basis syndrome was eponymously named. Genetic analysis demonstrated that 51/56 families to be unrelated. In FGFR3 gene 10/TM location of 1172 the nucleotide changes C>A, Ala 391 Glu 19/56 and Exon-19, 5q35.2 at conserved linker region the changes occurred pro 246 Arg in 25/56 families. Independent genetic origins, but phenotypic similarities in the 51 families add to the evidence supporting the theory of selfish spermatogonial selective advantage for this rare gain-of-function FGFR2 mutation.

  17. A novel mouse Fgfr2 mutant, hobbyhorse (hob, exhibits complete XY gonadal sex reversal.

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    Pam Siggers

    Full Text Available The secreted molecule fibroblast growth factor 9 (FGF9 plays a critical role in testis determination in the mouse. In embryonic gonadal somatic cells it is required for maintenance of SOX9 expression, a key determinant of Sertoli cell fate. Conditional gene targeting studies have identified FGFR2 as the main gonadal receptor for FGF9 during sex determination. However, such studies can be complicated by inefficient and variable deletion of floxed alleles, depending on the choice of Cre deleter strain. Here, we report a novel, constitutive allele of Fgfr2, hobbyhorse (hob, which was identified in an ENU-based forward genetic screen for novel testis-determining loci. Fgr2hob is caused by a C to T mutation in the invariant exon 7, resulting in a polypeptide with a mis-sense mutation at position 263 (Pro263Ser in the third extracellular immunoglobulin-like domain of FGFR2. Mutant homozygous embryos show severe limb and lung defects and, when on the sensitised C57BL/6J (B6 genetic background, undergo complete XY gonadal sex reversal associated with failure to maintain expression of Sox9. Genetic crosses employing a null mutant of Fgfr2 suggest that Fgr2hob is a hypomorphic allele, affecting both the FGFR2b and FGFR2c splice isoforms of the receptor. We exploited the consistent phenotype of this constitutive mutant by analysing MAPK signalling at the sex-determining stage of gonad development, but no significant abnormalities in mutant embryos were detected.

  18. Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk

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    Carayol Jerome

    2010-02-01

    Full Text Available Abstract Background Autism is a complex disorder characterized by deficits involving communication, social interaction, and repetitive and restrictive patterns of behavior. Twin studies have shown that autism is strongly heritable, suggesting a strong genetic component. In other disease states with a complex etiology, such as type 2 diabetes, cancer and cardiovascular disease, combined analysis of multiple genetic variants in a genetic score has helped to identify individuals at high risk of disease. Genetic scores are designed to test for association of genetic markers with disease. Method The accumulation of multiple risk alleles markedly increases the risk of being affected, and compared with studying polymorphisms individually, it improves the identification of subgroups of individuals at greater risk. In the present study, we show that this approach can be applied to autism by specifically looking at a high-risk population of children who have siblings with autism. A two-sample study design and the generation of a genetic score using multiple independent genes were used to assess the risk of autism in a high-risk population. Results In both samples, odds ratios (ORs increased significantly as a function of the number of risk alleles, with a genetic score of 8 being associated with an OR of 5.54 (95% confidence interval [CI] 2.45 to 12.49. The sensitivities and specificities for each genetic score were similar in both analyses, and the resultant area under the receiver operating characteristic curves were identical (0.59. Conclusions These results suggest that the accumulation of multiple risk alleles in a genetic score is a useful strategy for assessing the risk of autism in siblings of affected individuals, and may be better than studying single polymorphisms for identifying subgroups of individuals with significantly greater risk.

  19. Fine-Scale Mapping of the FGFR2 Breast Cancer Risk Locus

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    Meyer, Kerstin B; O'Reilly, Martin; Michailidou, Kyriaki

    2013-01-01

    The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of...

  20. Activation of p38 MAPK pathway in the skull abnormalities of Apert syndrome Fgfr2+P253R mice

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    Hill Cheryl A

    2010-02-01

    Full Text Available Abstract Background Apert syndrome is characterized by craniosynostosis and limb abnormalities and is primarily caused by FGFR2 +/P253R and +/S252W mutations. The former mutation is present in approximately one third whereas the latter mutation is present in two-thirds of the patients with this condition. We previously reported an inbred transgenic mouse model with the Fgfr2 +/S252W mutation on the C57BL/6J background for Apert syndrome. Here we present a mouse model for the Fgfr2+/P253R mutation. Results We generated inbred Fgfr2+/P253R mice on the same C56BL/6J genetic background and analyzed their skeletal abnormalities. 3D micro-CT scans of the skulls of the Fgfr2+/P253R mice revealed that the skull length was shortened with the length of the anterior cranial base significantly shorter than that of the Fgfr2+/S252W mice at P0. The Fgfr2+/P253R mice presented with synostosis of the coronal suture and proximate fronts with disorganized cellularity in sagittal and lambdoid sutures. Abnormal osteogenesis and proliferation were observed at the developing coronal suture and long bones of the Fgfr2+/P253R mice as in the Fgfr2+/S252W mice. Activation of mitogen-activated protein kinases (MAPK was observed in the Fgfr2+/P253R neurocranium with an increase in phosphorylated p38 as well as ERK1/2, whereas phosphorylated AKT and PKCα were not obviously changed as compared to those of wild-type controls. There were localized phenotypic and molecular variations among individual embryos with different mutations and among those with the same mutation. Conclusions Our in vivo studies demonstrated that the Fgfr2 +/P253R mutation resulted in mice with cranial features that resemble those of the Fgfr2+/S252W mice and human Apert syndrome. Activated p38 in addition to the ERK1/2 signaling pathways may mediate the mutant neurocranial phenotype. Though Apert syndrome is traditionally thought to be a consistent phenotype, our results suggest localized and regional

  1. Recombinant expression in E. coli of human FGFR2 with its transmembrane and extracellular domains

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    Adam Bajinting

    2017-06-01

    Full Text Available Fibroblast growth factor receptors (FGFRs are a family of receptor tyrosine kinases containing three domains: an extracellular receptor domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. FGFRs are activated by fibroblast growth factors (FGFs as part of complex signal transduction cascades regulating angiogenesis, skeletal formation, cell differentiation, proliferation, cell survival, and cancer. We have developed the first recombinant expression system in E. coli to produce a construct of human FGFR2 containing its transmembrane and extracellular receptor domains. We demonstrate that the expressed construct is functional in binding heparin and dimerizing. Size exclusion chromatography demonstrates that the purified FGFR2 does not form a complex with FGF1 or adopts an inactive dimer conformation. Progress towards the successful recombinant production of intact FGFRs will facilitate further biochemical experiments and structure determination that will provide insight into how extracellular FGF binding activates intracellular kinase activity.

  2. Bent bone dysplasia (BBD)-FGFR2 type: the radiologic manifestations in early gestation

    Energy Technology Data Exchange (ETDEWEB)

    Handa, Atsuhiko; Okajima, Yuka; Kurihara, Yasuyuki [St. Luke' s International Hospital, Department of Radiology, Tokyo (Japan); Izumi, Noriko; Yamanaka, Michiko [St. Luke' s International Hospital, Department of Integrated Women' s Health, Tokyo (Japan)

    2016-02-15

    Bent bone dysplasia-fibroblast growth factor receptor 2 type (BBD-FGFR2) is a recently identified skeletal dysplasia caused by specific FGFR2 mutations, characterized by craniosynostosis and prenatal bowing of the long bones. Only a few cases have been published. We report an affected fetus terminated at 21 weeks of gestation. The clinical and radiologic manifestations mostly recapitulate previous descriptions; however we suggest additional hallmarks of this disorder in early gestation. These hallmarks include distinctive short, thick clavicles and wavy ribs, as well as vertebral bodies that showed striking anteroposterior shortening. Femoral fractures were also present in our case. Although craniosynostosis is a hallmark of the disease, clinicians should be aware that craniosynostosis might not be readily apparent on plain films early in gestation. (orig.)

  3. Apert Syndrome With FGFR2 758 C > G Mutation: A Chinese Case Report

    Directory of Open Access Journals (Sweden)

    Yahong Li

    2018-05-01

    Full Text Available Background: Apert syndrome is considered as one of the most common craniosynostosis syndromes with a prevalence of 1 in 65,000 individuals, and has a close relationship with point mutations in FGFR2 gene.Case report: Here, we described a Apert syndrome case, who was referred to genetic consultation in our hospital with the symptom of craniosynostosis and syndactyly of the hands and feet. Craniosynostosis, midfacial retrusion, steep wide forehead, larger head circumference, marked depression of the nasal bridge, short and wide nose and proptosis could be found obviously, apart from these, ears were mildly low compared with normal children and there was no cleft lip and palate. Mutation was identified by sanger sequencing and a mutation in the exon 7 of FGFR2 gene was detected: p.Pro253Arg (P253R 758 C > G, which was not found in his parents.Conclusion: The baby had Apert syndrome caused by 758 C > G mutation in the exon 7 of FGFR2 gene, considering no this mutation in his parents, it was spontaneous.

  4. Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zong-Sian, E-mail: gary810426@hotmail.com [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Liu, Che Fu, E-mail: s9823002@m98.nthu.edu.tw [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Fu, Brian, E-mail: brianfu9@gmail.com [Northwood High School, Irvine, CA (United States); Chou, Ruey-Hwang, E-mail: rhchou@mail.cmu.edu.tw [Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan (China); Department of Biotechnology, Asia University, Taiwan (China); Yu, Chin, E-mail: cyu.nthu@gmail.com [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China)

    2016-09-02

    The extracellular portion of the human fibroblast growth factor receptor2 D2 domain (FGFR2 D2) interacts with human fibroblast growth factor 1 (hFGF1) to activate a downstream signaling cascade that ultimately affects mitosis and differentiation. Suramin is an antiparasiticdrug and a potent inhibitor of FGF-induced angiogenesis. Suramin has been shown to bind to hFGF1, and might block the interaction between hFGF1 and FGFR2 D2. Here, we titrated hFGF1 with FGFR2 D2 and suramin to elucidate their interactions using the detection of NMR. The docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed. The results indicate that suramin blocks the interaction between hFGF1 and FGFR2 D2. We used the PyMOL software to show the hydrophobic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. The results will be useful for the development of new antimitogenic activity drugs. - Highlights: • The interfacial residues on hFGF1-FGFR2 D2 and hFGF1-Suramin contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • hFGF1-FGFR2 D2 and hFGF1-Suramin complex models were generated from NMR restraints by using HADDOCK program. • We analyzed hFGF1-Suramin complex models and found the interaction between hFGF1-Suramin is hydrophobic. • The bioactivity of the hFGF1-FGFR2 D2 and hFGF1-Suramin complex was studied by using WST1 assay.

  5. Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity

    International Nuclear Information System (INIS)

    Wu, Zong-Sian; Liu, Che Fu; Fu, Brian; Chou, Ruey-Hwang; Yu, Chin

    2016-01-01

    The extracellular portion of the human fibroblast growth factor receptor2 D2 domain (FGFR2 D2) interacts with human fibroblast growth factor 1 (hFGF1) to activate a downstream signaling cascade that ultimately affects mitosis and differentiation. Suramin is an antiparasiticdrug and a potent inhibitor of FGF-induced angiogenesis. Suramin has been shown to bind to hFGF1, and might block the interaction between hFGF1 and FGFR2 D2. Here, we titrated hFGF1 with FGFR2 D2 and suramin to elucidate their interactions using the detection of NMR. The docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed. The results indicate that suramin blocks the interaction between hFGF1 and FGFR2 D2. We used the PyMOL software to show the hydrophobic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. The results will be useful for the development of new antimitogenic activity drugs. - Highlights: • The interfacial residues on hFGF1-FGFR2 D2 and hFGF1-Suramin contact surface were mapped by "1H-"1"5N HSQC experiments. • hFGF1-FGFR2 D2 and hFGF1-Suramin complex models were generated from NMR restraints by using HADDOCK program. • We analyzed hFGF1-Suramin complex models and found the interaction between hFGF1-Suramin is hydrophobic. • The bioactivity of the hFGF1-FGFR2 D2 and hFGF1-Suramin complex was studied by using WST1 assay.

  6. Differential effects of FGFR2 mutations on syndactyly and cleft palate in Apert syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Slaney, S.F.; Oldridge, M.; Wilkie, A.O.M. [Univ. of Oxford (United Kingdom)] [and others

    1996-05-01

    Apert syndrome is a distinctive human malformation characterized by craniosynostosis and severe syndactyly of the hands and feet. It is caused by specific missense substitutions involving adjacent amino acids (Ser252Trp or Pro253Arg) in the linker between the second and third extracellular immunoglobulin domains of fibroblast growth factor receptor 2 (FGFR2). We have developed a simple PCR assay for these mutations in genomic DNA, based on the creation of novel SfiI and BstUI restriction sites. Analysis of DNA from 70 unrelated patients with Apert syndrome showed that 45 had the Ser252Trp mutation and 25 had the Pro253Arg mutation. Phenotypic differences between these two groups of patients were investigated. Significant differences were found for severity of syndactyly and presence of cleft palate. The syndactyly was more severe with the Pro253Arg mutation, for both the hands and the feet. In contrast, cleft palate was significantly more common in the Ser252Trp patients. No convincing differences were found in the prevalence of other malformations associated with Apert syndrome. We conclude that, although the phenotype attributable to the two mutations is very similar, there are subtle differences. The opposite trends for severity of syndactyly and cleft palate in relation to the two mutations may relate to the varying patterns of temporal and tissue-specific expression of different fibroblast growth factors, the ligands for FGFR2. 54 refs., 5 figs., 3 tabs.

  7. Generation of high-affinity, internalizing anti-FGFR2 single-chain variable antibody fragment fused with Fc for targeting gastrointestinal cancers.

    Science.gov (United States)

    Borek, Aleksandra; Sokolowska-Wedzina, Aleksandra; Chodaczek, Grzegorz; Otlewski, Jacek

    2018-01-01

    Fibroblast growth factor receptors (FGFRs) are promising targets for antibody-based cancer therapies, as their substantial overexpression has been found in various tumor cells. Aberrant activation of FGF receptor 2 (FGFR2) signaling through overexpression of FGFR2 and/or its ligands, mutations, or receptor amplification has been reported in multiple cancer types, including gastric, colorectal, endometrial, ovarian, breast and lung cancer. In this paper, we describe application of the phage display technology to produce a panel of high affinity single chain variable antibody fragments (scFvs) against the extracellular ligand-binding domain of FGFR2 (ECD_FGFR2). The binders were selected from the human single chain variable fragment scFv phage display libraries Tomlinson I + J and showed high specificity and binding affinity towards human FGFR2 with nanomolar KD values. To improve the affinity of the best binder selected, scFvF7, we reformatted it to a bivalent diabody format, or fused it with the Fc region (scFvF7-Fc). The scFvF7-Fc antibody construct presented the highest affinity for FGFR2, with a KD of 0.76 nM, and was selectively internalized into cancer cells overexpressing FGFR2, Snu-16 and NCI-H716. Finally, we prepared a conjugate of scFvF7-Fc with the cytotoxic drug monomethyl-auristatin E (MMAE) and evaluated its cytotoxicity. The conjugate delivered MMAE selectively to FGFR2-positive tumor cells. These results indicate that scFvF7-Fc-vcMMAE is a highly potent molecule for the treatment of cancers with FGFR2 overexpression.

  8. Computational mouse atlases and their application to automatic assessment of craniofacial dysmorphology caused by the Crouzon mutation Fgfr2

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Darvann, Tron Andre; Hermann, Nuno V.

    2007-01-01

    Crouzon syndrome is characterised by premature fusion of sutures and synchondroses. Recently the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of Micro CT scann....... Furthermore, the nonrigid approach is essential when it comes to analysing local, nonlinear shape differences.......Crouzon syndrome is characterised by premature fusion of sutures and synchondroses. Recently the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of Micro CT....... Subsequently, the atlas was deformed to match each subject from the two groups of mice. The accuracy of these registrations was measured by a comparison of manually placed landmarks from two different observers and automatically assessed landmarks. Both of the automatic approaches were within the inter...

  9. Apert Syndrome: Molecularly Confirmed C.758C>G (P.Pro253Arg) in FGFR2

    Energy Technology Data Exchange (ETDEWEB)

    Cha Gon, Lee, E-mail: leechagon@eulji.ac.kr [Department of Pediatrics, Eulji General Hospital, College of Medicine, Eulji University, 68 Hangeulbiseok-ro, Nowon-gu, Seoul 139-711 (Korea, Republic of)

    2016-03-21

    A 5-day-old girl was referred to our clinic for evaluation of congenital malformations. She was identified with a pathogenic mutation c.758C>G (p.Pro253Arg) in FGFR2 gene using targeted exome sequencing. The de novo mutation was confirmed with Sanger sequencing in the patient and her parents. She showed occipital plagiocephaly with frontal bossing (Figure A and B). Skull frontal and lateral radiography revealed fusion of most of the sutures except coronal suture, with convolutional markings (Figure D and E). She had complete cleft palate (Figure C). Her fused bilateral hands showed type II syndactyly with complete syndactyly between the ring and the little fingers (Figure F1-F3). Both toes were simple syndactyly with side-to-side fusion of skin (Figure G1-)

  10. Apert Syndrome: Molecularly Confirmed C.758C>G (P.Pro253Arg) in FGFR2

    International Nuclear Information System (INIS)

    Cha Gon, Lee

    2016-01-01

    A 5-day-old girl was referred to our clinic for evaluation of congenital malformations. She was identified with a pathogenic mutation c.758C>G (p.Pro253Arg) in FGFR2 gene using targeted exome sequencing. The de novo mutation was confirmed with Sanger sequencing in the patient and her parents. She showed occipital plagiocephaly with frontal bossing (Figure A and B). Skull frontal and lateral radiography revealed fusion of most of the sutures except coronal suture, with convolutional markings (Figure D and E). She had complete cleft palate (Figure C). Her fused bilateral hands showed type II syndactyly with complete syndactyly between the ring and the little fingers (Figure F1-F3). Both toes were simple syndactyly with side-to-side fusion of skin (Figure G1-)

  11. Low Risk Anomalies?

    DEFF Research Database (Denmark)

    Schneider, Paul; Wagner, Christian; Zechner, Josef

    . Empirically, we find that option-implied ex-ante skewness is strongly related to ex-post residual coskewness and alphas. Beta- and volatility-based low risk anomalies are largely driven by a single principal component, which is in turn largely explained by skewness. Controlling for skewness renders the alphas......This paper shows that stocks' CAPM alphas are negatively related to CAPM betas if investors demand compensation for negative skewness. Thus, high (low) beta stocks appear to underperform (outperform). This apparent anomaly merely reflects compensation for residual coskewness ignored by the CAPM...... of betting-against-beta and -volatility insignificant....

  12. Low Risk Anomalies?

    DEFF Research Database (Denmark)

    Schneider, Paul; Wagner, Christian; Zechner, Josef

    This paper shows theoretically and empirically that beta- and volatility-based low risk anomalies are driven by return skewness. The empirical patterns concisely match the predictions of our model that endogenizes the role of skewness for stock returns through default risk. With increasing downside...... risk, the standard capital asset pricing model (CAPM) increasingly overestimates expected equity returns relative to firms' true (skew-adjusted) market risk. Empirically, the profitability of betting against beta/volatility increases with firms' downside risk, and the risk-adjusted return differential...... of betting against beta/volatility among low skew firms compared to high skew firms is economically large. Our results suggest that the returns to betting against beta or volatility do not necessarily pose asset pricing puzzles but rather that such strategies collect premia that compensate for skew risk...

  13. Formation of intestinal atresias in the Fgfr2IIIb-/- mice is not associated with defects in notochord development or alterations in Shh expression.

    Science.gov (United States)

    Reeder, Amy L; Botham, Robert A; Franco, Marta; Zaremba, Krzysztof M; Nichol, Peter F

    2012-09-01

    The etiology of intestinal atresia remains elusive but has been ascribed to a number of possible events including in utero vascular accidents, failure of recanalization of the intestinal lumen, and mechanical compression. Another such event that has been postulated to be a cause in atresia formation is disruption in notochord development. This hypothesis arose from clinical observations of notochord abnormalities in patients with intestinal atresias as well as abnormal notochord development observed in a pharmacologic animal model of intestinal atresia. Atresias in this model result from in utero exposure to Adriamycin, wherein notochord defects were noted in up to 80% of embryos that manifested intestinal atresias. Embryos with notochord abnormalities were observed to have ectopic expression of Sonic Hedgehog (Shh), which in turn was postulated to be causative in atresia formation. We were interested in determining whether disruptions in notochord development or Shh expression occurred in an established genetic model of intestinal atresia and used the fibroblast growth factor receptor 2IIIb homozygous mutant (Fgfr2IIIb-/-) mouse model. These embryos develop colonic atresias (100% penetrance) and duodenal atresias (42% penetrance). Wild-type and Fgfr2IIIb-/- mouse embryos were harvested at embryonic day (E) 10.5, E11.5, E12.5, and E13.5. Whole-mount in situ hybridization was performed on E10.5 embryos for Shh. Embryos at each time point were harvested and sectioned for hematoxylin-eosin staining. Sections were photographed specifically for the notochord and resulting images reconstructed in 3-D using Amira software. Colons were isolated from wild-type and Fgfr2IIIb-/- embryos at E10.5, then cultured for 48 hours in Matrigel with FGF10 in the presence or absence of exogenous Shh protein. Explants were harvested, fixed in formalin, and photographed. Fgfr2IIIb-/- mouse embryos exhibit no disruptions in Shh expression at E10.5, when the first events in atresia

  14. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    International Nuclear Information System (INIS)

    Riaz, Muhammad; Elstrodt, Fons; Hollestelle, Antoinette; Dehghan, Abbas; Klijn, Jan GM; Schutte, Mieke

    2009-01-01

    Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines

  15. p.Ser252Trp and p.Pro253Arg mutations in FGFR2 gene causing Apert syndrome: the first clinical and molecular report of Indonesian patients.

    Science.gov (United States)

    Mundhofir, Farmaditya E P; Sistermans, Erik A; Faradz, Sultana M H; Hamel, Ben C J

    2013-03-01

    Apert syndrome (AS) is a rare autosomal dominant disorder characterised by craniosynostosis and limb malformations, and is associated with congenital heart disease and other systemic malformations, including intellectual disability. We report two Indonesian patients with AS, in whom molecular analysis detected p.Ser252Trp (c.755C>G) and p.Pro253Arg (c.758C>G) mutations in the fibroblast growth factor receptor 2 (FGFR2) gene, respectively. Although the syndrome has been frequently described, this is the first clinical report of AS confirmed by molecular analysis in Indonesia. The difference in severity of clinical features in the two patients may be consistent with a genotype-phenotype correlation of the FGFR2mutation. The management of individuals with AS is best achieved within a multidisciplinary setting. However, in most developing countries, early intervention may be delayed due to late diagnosis, a lack of facilities and financial constraints. This report underpins the benefits of early diagnosis for AS management.

  16. Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Nayak, Seema; Goel, Madhu Mati; Makker, Annu; Bhatia, Vikram; Chandra, Saumya; Kumar, Sandeep; Agarwal, S P

    2015-01-01

    There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP.

  17. Spared pre-irradiated area in pustular lesions induced by icotinib showing decreased expressions of CD1a+ langerhans cells and FGFR2

    International Nuclear Information System (INIS)

    Zhao Qiong; Wang Yi Na; Wang Bo

    2013-01-01

    Icotinib hydrochloride, a novel inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved by the State Food and Drug Administration for the treatment of advanced non-small-cell lung cancer. Up to date, cutaneous response to icotinib is largely unknown. Here we report an uncommon lesional phenomenon in a 56-year-old Chinese male with non-small-cell lung cancer, who received icotinib as a second-line treatment. Characteristic papulopustular rash on the chest and back was observed 4 days later. Interestingly, the rash completely spares a pre-irradiated area. The immunohistochemical study in the lesional skin area and spared skin area revealed a significant decrease in CD1a + Langerhans cells, Ki-67 as well as FGFR2 in the spared area than in the lesional area. Thus, the present case indicated that loss of the basal layer of proliferative cells and antigen-presenting cells (Langerhans cell), as well as the down-regulation of FGFR2 signaling in the pre-irradiated skin area, may join forces in inhibiting icotinib-associated cutaneous reactions. To our knowledge, this is the first report of both lesional area and lesion-spared area in a Chinese male receiving treatment with a new epidermal growth factor receptor-tyrosine kinase inhibitor (icotinib). The immunohistochemical reactions described here also provide new insight into the pathogenesis of epidermal growth factor receptor-tyrosine kinase inhibitor-related skin toxicities, and the role that other tyrosine kinase receptors (including FGFR) played in non-small-cell lung cancer. (author)

  18. Spared pre-irradiated area in pustular lesions induced by icotinib showing decreased expressions of CD1a+ langerhans cells and FGFR2.

    Science.gov (United States)

    Zhao, Qiong; Wang, Yi Na; Wang, Bo

    2013-02-01

    Icotinib hydrochloride, a novel inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved by the State Food and Drug Administration for the treatment of advanced non-small-cell lung cancer. Up to date, cutaneous response to icotinib is largely unknown. Here we report an uncommon lesional phenomenon in a 56-year-old Chinese male with non-small-cell lung cancer, who received icotinib as a second-line treatment. Characteristic papulopustular rash on the chest and back was observed 4 days later. Interestingly, the rash completely spares a pre-irradiated area. The immunohistochemical study in the lesional skin area and spared skin area revealed a significant decrease in CD1a(+) Langerhans cells, Ki-67 as well as FGFR2 in the spared area than in the lesional area. Thus, the present case indicated that loss of the basal layer of proliferative cells and antigen-presenting cells (Langerhans cell), as well as the down-regulation of FGFR2 signaling in the pre-irradiated skin area, may join forces in inhibiting icotinib-associated cutaneous reactions. To our knowledge, this is the first report of both lesional area and lesion-spared area in a Chinese male receiving treatment with a new epidermal growth factor receptor-tyrosine kinase inhibitor (icotinib). The immunohistochemical reactions described here also provide new insight into the pathogenesis of epidermal growth factor receptor-tyrosine kinase inhibitor-related skin toxicities, and the role that other tyrosine kinase receptors (including FGFR) played in non-small-cell lung cancer.

  19. Deformed Skull Morphology Is Caused by the Combined Effects of the Maldevelopment of Calvarias, Cranial Base and Brain in FGFR2-P253R Mice Mimicking Human Apert Syndrome.

    Science.gov (United States)

    Luo, Fengtao; Xie, Yangli; Xu, Wei; Huang, Junlan; Zhou, Siru; Wang, Zuqiang; Luo, Xiaoqing; Liu, Mi; Chen, Lin; Du, Xiaolan

    2017-01-01

    Apert syndrome (AS) is a common genetic syndrome in humans characterized with craniosynostosis. Apert patients and mouse models showed abnormalities in sutures, cranial base and brain, that may all be involved in the pathogenesis of skull malformation of Apert syndrome. To distinguish the differential roles of these components of head in the pathogenesis of the abnormal skull morphology of AS, we generated mouse strains specifically expressing mutant FGFR2 in chondrocytes, osteoblasts, and progenitor cells of central nervous system (CNS) by crossing Fgfr2 +/P253R-Neo mice with Col2a1-Cre, Osteocalcin-Cre (OC-Cre), and Nestin-Cre mice, respectively. We then quantitatively analyzed the skull and brain morphology of these mutant mice by micro-CT and micro-MRI using Euclidean distance matrix analysis (EDMA). Skulls of Col2a1-Fgfr2 +/P253R mice showed Apert syndrome-like dysmorphology, such as shortened skull dimensions along the rostrocaudal axis, shortened nasal bone, and evidently advanced ossification of cranial base synchondroses. The OC-Fgfr2 +/P253R mice showed malformation in face at 8-week stage. Nestin-Fgfr2 +/P253R mice exhibited increased dorsoventral height and rostrocaudal length on the caudal skull and brain at 8 weeks. Our study indicates that the abnormal skull morphology of AS is caused by the combined effects of the maldevelopment in calvarias, cranial base, and brain tissue. These findings further deepen our knowledge about the pathogenesis of the abnormal skull morphology of AS, and provide new clues for the further analyses of skull phenotypes and clinical management of AS.

  20. The effects of tissue-non-specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of Crouzon craniosynostosis.

    Science.gov (United States)

    Wang, E; Nam, H K; Liu, J; Hatch, N E

    2015-04-01

    Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-non-specific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. Neonatal Crouzon (FGFRC342Y/+) and wild-type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at 4 weeks postnatal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology were assessed by micro-computed tomography. Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphological analysis revealed craniofacial form differences for inferior surface (p=0.023) and cranial height (p=0.014) regions between TNAP lentivirus-injected and vehicle-injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p=0.068). These results suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Low-Risk Investing without Industry Bets

    DEFF Research Database (Denmark)

    Asness, Clifford S.; Frazzini, Andrea; Heje Pedersen, Lasse

    2014-01-01

    The strategy of buying safe low-beta stocks while shorting (or underweighting) riskier high-beta stocks (“betting against beta”) has been shown to deliver significant risk-adjusted returns. Some have suggested, however, that such “low-risk investing” delivers high returns primarily because...... of industry bets that favor a slowly changing set of stodgy, stable industries. The authors refute this notion by showing that a strategy of betting against beta has delivered positive returns both as an industry-neutral bet within each industry and as a pure bet across industries....

  2. Cellulase variants

    Science.gov (United States)

    Blazej, Robert; Toriello, Nicholas; Emrich, Charles; Cohen, Richard N.; Koppel, Nitzan

    2015-07-14

    This invention provides novel variant cellulolytic enzymes having improved activity and/or stability. In certain embodiments the variant cellulotyic enzymes comprise a glycoside hydrolase with or comprising a substitution at one or more positions corresponding to one or more of residues F64, A226, and/or E246 in Thermobifida fusca Cel9A enzyme. In certain embodiments the glycoside hydrolase is a variant of a family 9 glycoside hydrolase. In certain embodiments the glycoside hydrolase is a variant of a theme B family 9 glycoside hydrolase.

  3. 40 CFR 266.109 - Low risk waste exemption.

    Science.gov (United States)

    2010-07-01

    ... MANAGEMENT FACILITIES Hazardous Waste Burned in Boilers and Industrial Furnaces § 266.109 Low risk waste exemption. (a) Waiver of DRE standard. The DRE standard of § 266.104(a) does not apply if the boiler or... 99.9 percent destruction and removal efficiency. That is, assume that 0.1 percent of the mass weight...

  4. Contemporary management of low-risk bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Witjes, J.A.

    2011-01-01

    Bladder cancer comprises a heterogeneous group of tumors, the majority of which are non-muscle-invasive bladder cancer (NMIBC) at initial presentation. Low-risk bladder cancer--defined as pTa low-grade papillary tumors--is the type of NMIBC with the most favorable oncologic outcome. Although the

  5. Determinants of low risk of asthma exacerbation during pregnancy

    DEFF Research Database (Denmark)

    Ali, Z; Nilas, L; Ulrik, C S

    2018-01-01

    of Asthma during Pregnancy (MAP) programme at Hvidovre Hospital since 2007. Assessment of asthma control, adjustment of treatment, spirometry and measurement of exhaled nitric oxide (FENO) were performed, and baseline characteristics and exacerbation history were collected at enrolment. Determinants of low......: Clinically stable asthma at enrolment, together with no history of previous exacerbations and no prescribed controller medication, is a determinant of low risk of an asthma exacerbation during pregnancy, which may guide clinicians in individualizing surveillance of asthma during pregnancy.......BACKGROUND: Assessment of asthma control every 4-6 weeks during pregnancy is recommended to reduce risk of exacerbation, and by that improve outcome. OBJECTIVE: To identify determinants of pregnancies with low risk of asthma exacerbation. METHODS: All pregnant women enrolled into the Management...

  6. Emergency caesarean section in low risk nulliparous women

    DEFF Research Database (Denmark)

    Haerskjold, Ann; Hegaard, H K; Kjaergaard, H

    2012-01-01

    and identifies maternal and fetal risk factors associated with ECS. We included 2,748 low-risk women and 8.7% had ECS. Failure-to-progress (FTP) accounted for 68.3% of the ECS and 30.4% were performed due to suspected fetal distress (SFD). Multivariate logistic regression analyses were done to estimate.......26-3.20) were associated with increased risk of ECS due to FTP....

  7. Holoprosencephaly Variant

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-01-01

    Full Text Available The clinical manifestations in 15 patients (6 boys and 9 girls with middle interhemispheric variant (MIH of holoprosencephaly (HPE were compared with classic subtypes (alobar, semilobar, and lobar of HPE in a multicenter study at Stanford University School of Medicine and Lucile Packard Children’s Hospital; Children’s Hospital of Philadelphia; University of California at San Francisco; Texas Scottish Rite Hospital, Dallas; and Kennedy Krieger Institute, Baltimore, MD.

  8. Determinants for hospitalization in " low-risk" community acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Aliyu Muktar H

    2003-06-01

    Full Text Available Abstract Background A variable decision in managing community acquired pneumonia (CAP is the initial site of care; in-patient versus outpatient. These variations persist despite comprehensive practice guidelines. Patients with a Pneumonia Severity Index (PSI score lower than seventy have low risk for complications and outpatient antibiotic management is recommended in this group. These patients are generally below the age of fifty years, non-nursing home residents, HIV negative and have no major cardiac, hepatic, renal or malignant diseases. Methods A retrospective analysis of 296 low-risk CAP patients evaluated within a year one period at St. Agnes Hospital, Baltimore, Maryland was undertaken. All patients were assigned a PSI score. 208 (70% were evaluated and discharged from the emergency department (E.D. to complete outpatient antibiotic therapy, while 88 (30% were hospitalized. Patients were sub-stratified into classes I-V according to PSI. A comparison of demographic, clinical, social and financial parameters was made between the E.D. discharged and hospitalized groups. Results Statistically significant differences in favor of the hospitalized group were noted for female gender (CI: 1.46-5.89, p= 0.0018, African Americans (CI: 0.31-0.73, p= 0.004, insurance coverage (CI: 0.19-0.63, p= 0.0034, temperature (CI: 0.04-0.09, p= 0.0001 and pulse rate (CI: 0.03-0.14, p= 0.0001. No statistically significant differences were observed between the two groups for altered mental status, hypotension, tachypnea, laboratory/radiological parameters and social indicators (p>0.05. The average length of stay for in-patients was 3.5 days at about eight time's higher cost than outpatient management. There was no difference in mortality or treatment failures between the two groups. The documentation rate and justifications for hospitalizing low risk CAP patients by admitting physicians was less than optimal. Conclusions High fever, tachycardia, female gender

  9. Comparison between visual and computerized cardiotocography in low risk pregnancy

    International Nuclear Information System (INIS)

    Mirghani, Hisham M.; Khair, Howaida

    2005-01-01

    To compare between visual and computerized cardiotocography (cCTG) in low-risk pregnant women in predicting pregnancy outcome. One hundred and fifty-three consecutive computerized fetal heart tracings were recorded from non-laboring pregnant women at >/- 30 weeks gestation. All traces were reviewed by 2 experienced obstetricians. The study was carried out at Al-Ain Medical District, United Arab Emirates, between August 2004 and December 2004. Of the 153 pregnant women, 11 (7.2%) were delivered by cesarean section. The interobserver agreement was 0.60. The observers cCTG agreement were 0.48 and 0.45. The difference in cesarean section rate was not statistically significant. Observers interpretation and cCTG did not correlate well with Apgar score at 5 minutes and admission to special care baby unit. Computerized CTG has little advantage over conventional CTG in the prediction of Apgar score and need for neonatal intensive care unit admission in a low-risk population. (author)

  10. Selection of low-risk design guidelines for energetic events

    International Nuclear Information System (INIS)

    Ferguson, D.; Marchaterre, J.; Graham, J.

    1982-01-01

    This paper recommends the establishment of specific design guidelines for protection against potential, but low-probability, energetic events. These guidelines recognize the plant protective features incorporated to prevent such events, as well as the inherent capability of the plant to accommodate a certain level of energy release. Further, their application is recommended within the context of necessary standardized and agreed-upon acceptance criteria which are less restrictive than ASME code requirements. The paper provides the background upon which the selection of the design is made, including the characterization of energetic events dependent on various core-design parameters, and including the necessity of a low-risk design balanced between prevention of accidents and the mitigation of consequences

  11. Low-risk diet for colorectal cancer in Italy.

    Science.gov (United States)

    Calza, S; Ferraroni, M; La Vecchia, C; Franceschi, S; Decarli, A

    2001-12-01

    An innovative approach was used to define a low-risk diet for colorectal cancer from a multicentric case-control study of 1953 incident cases and 4154 hospital controls from Italy. A logistic regression model was fitted on the reported intake of five macronutrients, and the estimated coefficients were used to compute a diet-related logistic risk score (LRS). The mean of LRS within risk decile ranged from 0.89 to 1.86. Total energy intake and absolute consumption of each macronutrient increased with increasing LRS. In relative terms, however, starch intake showed an almost threefold increase across subsequent score levels, while a decline was observed for unsaturated fat, sugar and protein. Saturated fat consumption remained fairly stable in relative terms. When food groups were considered, bread and cereals dishes, cakes and desserts and refined sugar were positively associated, while the consumption of vegetables, fruit, fish, poultry and olive oils was inversely associated with LRS.

  12. 38 CFR 41.530 - Criteria for a low-risk auditee.

    Science.gov (United States)

    2010-07-01

    ... low-risk auditee and be eligible for reduced audit coverage in accordance with § 41.520: (a) Single... entity that has biennial audits does not qualify as a low-risk auditee, unless agreed to in advance by... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Criteria for a low-risk...

  13. Low-risk diet for breast cancer in Italy.

    Science.gov (United States)

    Franceschi, S; La Vecchia, C; Russo, A; Negri, E; Favero, A; Decarli, A

    1997-11-01

    To define a low-risk diet for breast cancer in Italy, a multicentric case-control study of 2569 incident cases of breast cancer and 2588 controls from Italy was analyzed. A logistic regression model was applied to the estimated intake of five macronutrients and used to compute a diet-related risk score (RS). The pattern of macronutrient and food group intake across RS deciles was defined. The mean of diet-related RSs across subsequent risk deciles ranged from 0.83 to 1.44. Total energy intake first decreased slightly, from the first to the second decile, and then increased, mostly in the last three risk deciles. Intake of starch increased in absolute and relative terms, whereas saturated fat intake rose in absolute terms but remained stable as a proportion. A relative decline was observed for unsaturated fat and sugars, with a hint, however, of U-shape effect. From a food group viewpoint, there was a marked increase in the intake of bread and cereal dishes, cakes and desserts, and refined sugar across subsequent deciles, whereas the consumption of vegetables, olive and seed oils, and fruit decreased.

  14. Lack of international consensus in low-risk drinking guidelines.

    Science.gov (United States)

    Furtwaengler, Nina A F F; de Visser, Richard O

    2013-01-01

    To encourage moderate alcohol consumption, many governments have developed guidelines for alcohol intake, guidelines for alcohol consumption during pregnancy and legislation relating to blood alcohol limits when driving. The aim of this study was to determine the degree of international consensus within such guidelines. Official definitions of standard drinks and consumption guidelines were searched for on government websites, including all 27 European Union Member States and countries from all global geographic regions. There was a remarkable lack of agreement about what constitutes harmful or excessive alcohol consumption on a daily basis, a weekly basis and when driving, with no consensus about the ratios of consumption guidelines for men and women. International consensus in low-risk drinking guidelines is an important--and achievable--goal. Such agreement would facilitate consistent labelling of packaged products and could help to promote moderate alcohol consumption. However, there are some paradoxes related to alcohol content labelling and people's use of such information: although clearer information could increase people's capacity to monitor and regulate their alcohol consumption, not all drinkers are motivated to drink moderately or sensibly, and drinkers who intend to get drunk may use alcohol content labelling to select more alcoholic products. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  15. Home birth or short-stay hospital birth in a low risk population in The Netherlands.

    NARCIS (Netherlands)

    Wiegers, T.A.; Zee, J. van der; Kerssens, J.J.; Keirse, M.J.N.C.

    1998-01-01

    In the Netherlands women with low risk pregnancies can choose whether they want to give birth at home or in hospital, under the care of their own primary caregiver. The majority of these women prefer to give birth at home, but over the last few decades an increasing number of low risk women have

  16. Nonvisible tumors on multiparametric magnetic resonance imaging does not predict low-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Seung Hwan Lee

    2015-12-01

    Conclusions: Even though cancer foci were not visualized by postbiopsy MRI, the pathological tumor volumes and extent of GS upgrading were relatively high. Therefore, nonvisible tumors by multiparametric MRI do not appear to be predictive of low-risk PCA.

  17. CDKL5 variants

    Science.gov (United States)

    Kalscheuer, Vera M.; Hennig, Friederike; Leonard, Helen; Downs, Jenny; Clarke, Angus; Benke, Tim A.; Armstrong, Judith; Pineda, Mercedes; Bailey, Mark E.S.; Cobb, Stuart R.

    2017-01-01

    Objective: To provide new insights into the interpretation of genetic variants in a rare neurologic disorder, CDKL5 deficiency, in the contexts of population sequencing data and an updated characterization of the CDKL5 gene. Methods: We analyzed all known potentially pathogenic CDKL5 variants by combining data from large-scale population sequencing studies with CDKL5 variants from new and all available clinical cohorts and combined this with computational methods to predict pathogenicity. Results: The study has identified several variants that can be reclassified as benign or likely benign. With the addition of novel CDKL5 variants, we confirm that pathogenic missense variants cluster in the catalytic domain of CDKL5 and reclassify a purported missense variant as having a splicing consequence. We provide further evidence that missense variants in the final 3 exons are likely to be benign and not important to disease pathology. We also describe benign splicing and nonsense variants within these exons, suggesting that isoform hCDKL5_5 is likely to have little or no neurologic significance. We also use the available data to make a preliminary estimate of minimum incidence of CDKL5 deficiency. Conclusions: These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain. PMID:29264392

  18. Preventive dentistry: practitioners' recommendations for low-risk patients compared with scientific evidence and practice guidelines.

    Science.gov (United States)

    Frame, P S; Sawai, R; Bowen, W H; Meyerowitz, C

    2000-02-01

    The purpose of this article is to compare published evidence supporting procedures to prevent dental caries and periodontal disease, in low-risk patients, with the actual preventive recommendations of practicing dentists. Methods included (1) a survey questionnaire of general dentists practicing in western New York State concerning the preventive procedures they would recommend and at what intervals for low-risk children, young adults, and older adults; and (2) review of the published, English-language literature for evidence supporting preventive dental interventions. The majority of dentists surveyed recommended semiannual visits for visual examination and probing to detect caries (73% to 79%), and scaling and polishing to prevent periodontal disease (83% to 86%) for low-risk patients of all ages. Bite-wing radiographs were recommended for all age groups at annual or semiannual intervals. In-office fluoride applications were recommended for low-risk children at intervals of 6 to 12 months by 73% of dentists but were recommended for low-risk older persons by only 22% of dentists. Application of sealants to prevent pit and fissure caries was recommended for low-risk children by 22% of dentists. Literature review found no studies comparing different frequencies of dental examinations and bite-wing radiographs to determine the optimal screening interval in low-risk patients. Two studies of the effect of scaling and polishing on the prevention of periodontal disease found no benefit from more frequent than annual treatments. Although fluoride is clearly a major reason for the decline in the prevalence of dental caries, there are no studies of the incremental benefit of in-office fluoride treatments for low-risk patients exposed to fluoridated water and using fluoridated toothpaste. Comparative studies using outcome end points are needed to determine the optimal frequency of dental examinations and bite-wing radiographs for the early detection of caries, and of scaling

  19. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer.

    Directory of Open Access Journals (Sweden)

    Mia M Gaudet

    2010-10-01

    Full Text Available The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5 and 39 SNPs had p-values<10(-4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499 and chromosome 10 (rs16917302. The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR and 95% confidence intervals (CI for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, and for rs311499 was 0.72 (95% CI 0.61-0.85, . FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, . These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.

  20. Variants of cellobiohydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Bott, Richard R.; Foukaraki, Maria; Hommes, Ronaldus Wilhelmus; Kaper, Thijs; Kelemen, Bradley R.; Kralj, Slavko; Nikolaev, Igor; Sandgren, Mats; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander

    2018-04-10

    Disclosed are a number of homologs and variants of Hypocrea jecorina Ce17A (formerly Trichoderma reesei cellobiohydrolase I or CBH1), nucleic acids encoding the same and methods for producing the same. The homologs and variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted and/or deleted.

  1. Growth recovery lines are more common in infants at high vs. low risk for abuse

    International Nuclear Information System (INIS)

    Zapala, Matthew A.; Tsai, Andy; Kleinman, Paul K.

    2016-01-01

    Growth recovery lines, also known as growth arrest lines, are transverse radiodense metaphyseal bands that develop due to a temporary arrest of endochondral ossification caused by local or systemic insults. To determine if growth recovery lines are more common in infants at high risk versus low risk for abuse. Reports of American College of Radiology compliant skeletal surveys (1999-2013) were reviewed with clinical records. Infants at low risk for abuse had a skull fracture without significant intracranial injury, history of a fall and clinical determination of low risk (child protection team/social work assessment). Infants at high risk had significant intracranial injury, retinal hemorrhages, other skeletal injuries and clinical determination of high risk. There were 52 low-risk infants (mean: 4.7 months, range: 0.4-12 months) and 21 high-risk infants (mean: 4.2 months, range: 0.8-9.1 months). Two blinded radiologists independently evaluated the skeletal survey radiographs of the knees/lower legs for the presence of at least one growth recovery line. When growth recovery lines are scored as probably present or definitely present, their prevalence in the low-risk group was 38% (standard deviation [SD] = 8%; reader 1 = 17/52, reader 2 = 23/52) vs. 71% (SD = 7%; reader 1 = 16/21, reader 2 = 14/21) in the high-risk group (P < 0.001; odds ratio 4.0, 95% CI: 1.7-9.5). Growth recovery lines are encountered at a significantly higher rate in infants at high risk vs. low risk for abuse. This suggests that abused infants are prone to a temporary disturbance in endochondral ossification as a result of episodic physiological stresses. (orig.)

  2. Migraine Variants in Children

    Science.gov (United States)

    ... Headaches in Children FAQ Migraine Variants In Children Children Get Migraines Too! Learn More Migraine Information Find Help Doctors & Resources Get Connected Join the Conversation Follow Us on Social Media Company About News Resources Privacy Policy Contact Phone: ...

  3. Determinants of prenatal health care utilisation by low-risk women : A prospective cohort study

    NARCIS (Netherlands)

    Feijen-de Jong, Esther I.; Jansen, Danielle E. M. C.; Baarveld, Frank; Boerleider, Agatha W.; Spelten, Evelien; Schellevis, Francois; Reijneveld, Sijmen A.

    Background: Prenatal health care is pivotal in providing adequate prevention and care to pregnant women. Aim: We examined the determinants of inadequate prenatal health care utilisation by low-risk women in primary midwifery-led care in the Netherlands. Methods: We used longitudinal data from the

  4. Determinants of prenatal health care utilisation by low-risk women: a prospective cohort study.

    NARCIS (Netherlands)

    Feijen-de Jong, E.I.; Jansen, D.E.M.C.; Baarveld, F.; Boerleider, A.W.; Spelten, E.; Schellevis, F.; Reijneveld, S.A.

    2015-01-01

    Background: Prenatal health care is pivotal in providing adequate prevention and care to pregnant women. Aim: We examined the determinants of inadequate prenatal health care utilisation by low-risk women in primary midwifery-led care in the Netherlands. Methods: We used longitudinal data from the

  5. Determinants of prenatal health care utilisation by low-risk women: A prospective cohort study

    NARCIS (Netherlands)

    Feijen-de Jong, E.I.; Jansen, D.E.M.C.; Baarveld, F.; Boerleider, A.W.; Spelten, E.; Schellevis, F.; Reijneveld, S.A.

    2015-01-01

    Background: Prenatal health care is pivotal in providing adequate prevention and care to pregnant women. Aim: We examined the determinants of inadequate prenatal health care utilisation by low-risk women in primary midwifery-led care in the Netherlands. Methods: We used longitudinal data from the

  6. 29 CFR 99.530 - Criteria for a low-risk auditee.

    Science.gov (United States)

    2010-07-01

    ... management of Federal awards and provide a waiver. (c) There were no deficiencies in internal control which... periods) in which they were classified as Type A programs: (1) Internal control deficiencies which were... 29 Labor 1 2010-07-01 2010-07-01 true Criteria for a low-risk auditee. 99.530 Section 99.530 Labor...

  7. 7 CFR 3052.530 - Criteria for a low-risk auditee.

    Science.gov (United States)

    2010-01-01

    ... management of Federal awards and provide a waiver. (c) There were no deficiencies in internal control which... periods) in which they were classified as Type A programs: (1) Internal control deficiencies which were... 7 Agriculture 15 2010-01-01 2010-01-01 false Criteria for a low-risk auditee. 3052.530 Section...

  8. 76 FR 16234 - Prompt Corrective Action; Amended Definition of Low-Risk Assets

    Science.gov (United States)

    2011-03-23

    ...; Amended Definition of Low-Risk Assets AGENCY: National Credit Union Administration (NCUA). ACTION: Final... to reflect the absence of credit risk. Having considered the public comments addressing the Interim...), (f) and (g); 12 CFR 702.204(a)-(b). For a credit union that is subject to an additional Risk-Based...

  9. 75 FR 66298 - Prompt Corrective Action; Amended Definition of Low-Risk Assets

    Science.gov (United States)

    2010-10-28

    ...; Amended Definition of Low-Risk Assets AGENCY: National Credit Union Administration (NCUA). ACTION: Interim...-weighting of zero, reflecting the absence of credit risk. The amendment will expand the definition of ``low... exists today, the NGNs held by a natural person credit union would fall within the ``investments'' risk...

  10. Peripheral arterial tonometry cannot detect patients at low risk of coronary artery disease

    NARCIS (Netherlands)

    M.M. van den Heuvel (Mieke); O. Sorop (Oana); P. Musters (Paul); R.T. van Domburg (Ron); T.W. Galema (Tjebbe); D.J.G.M. Duncker (Dirk); W.J. van der Giessen (Wim); K. Nieman (Koen)

    2015-01-01

    textabstractBackground Endothelial dysfunction precedes coronary artery disease (CAD) and can be measured by peripheral arterial tonometry (PAT). We examined the applicability of PAT to detect a low risk of CAD in a chest pain clinic. Methods In 93 patients, PAT was performed resulting in reactive

  11. High- and Low-Risk Characteristics of Youth: The Five Cs of Competency.

    Science.gov (United States)

    McWhirter, J. Jeffries; And Others

    1994-01-01

    Identifies and discusses five basic skill strengths or skill deficits that mark critical difference between low-risk and high-risk youth. The "Five Cs of Competency" described include critical school competencies, concept of self and self-esteem, communication skills, coping ability, and control. Contends that these characteristics discriminate…

  12. Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH

    NARCIS (Netherlands)

    Meijers, Wouter C.; de Boer, Rudolf A.; van Veldhuisen, Dirk J.; Jaarsma, Tiny; Hillege, Hans L.; Maisel, Alan S.; Di Somma, Salvatore; Voors, Adriaan A.; Peacock, W. Frank

    2015-01-01

    AimTraditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization. Methods and resultsThis analysis was a substudy of The Coordinating Study Evaluating

  13. Active surveillance can reduce overtreatment in patients with low-risk prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebæk; Røder, Martin Andreas; Hvarness, Helle

    2013-01-01

    The incidence of prostate cancer in Denmark rose approximately 50% from 2000 to 2009 in parallel with the introduction of prostate-specific antigen (PSA)-testing. Available evidence indicates a significant overtreatment of patients with low-risk prostate cancer. Active surveillance has been...

  14. Client experiences with perinatal healthcare for high-risk and low-risk women

    NARCIS (Netherlands)

    van Stenus, Cherelle M.V.; Boere-Boonekamp, Magda M.; Kerkhof, Erna F.G.M.; Need, Ariana

    2018-01-01

    Problem: It is unknown if client experiences with perinatal healthcare differ between low-risk and high-risk women. Background: In the Netherlands, risk selection divides pregnant women into low- and high-risk groups. Receiving news that a pregnancy or childbirth has an increased likelihood of

  15. Bad experience, good birthing: Dutch low-risk pregnant women with a history of sexual abuse

    NARCIS (Netherlands)

    van der Hulst, Leonie A. M.; Bonsel, Gouke J.; Eskes, Martine; Birnie, Erwin; van Teijlingen, Edwin; Bleker, Otto P.

    2006-01-01

    OBJECTIVE: The long-term effects on women in childbirth with a history of sexual abuse have only been studied to a limited degree. We estimated the prevalence of lifetime experience among low-risk pregnant women (non-clinical) in The Netherlands as well as the association with (1) psycho-social

  16. Mother-Child Interactional Patterns in High- and Low-Risk Mothers.

    Science.gov (United States)

    Dolz, Laura; Cerezo, M. Angeles; Milner, Joel S.

    1997-01-01

    A study of 10 high-risk (of child physical abuse) and 10 demographically similar low-risk Spanish mother-child dyads investigated interactional patterns in the home. High-risk mothers made fewer neutral approaches to their children, displayed more negative behaviors toward their children, and made more indiscriminate responses to their children's…

  17. Identification of de novo copy number variants associated with human disorders of sexual development.

    Directory of Open Access Journals (Sweden)

    Mounia Tannour-Louet

    Full Text Available Disorders of sexual development (DSD, ranging in severity from genital abnormalities to complete sex reversal, are among the most common human birth defects with incidence rates reaching almost 3%. Although causative alterations in key genes controlling gonad development have been identified, the majority of DSD cases remain unexplained. To improve the diagnosis, we screened 116 children born with idiopathic DSD using a clinically validated array-based comparative genomic hybridization platform. 8951 controls without urogenital defects were used to compare with our cohort of affected patients. Clinically relevant imbalances were found in 21.5% of the analyzed patients. Most anomalies (74.2% evaded detection by the routinely ordered karyotype and were scattered across the genome in gene-enriched subtelomeric loci. Among these defects, confirmed de novo duplication and deletion events were noted on 1p36.33, 9p24.3 and 19q12-q13.11 for ambiguous genitalia, 10p14 and Xq28 for cryptorchidism and 12p13 and 16p11.2 for hypospadias. These variants were significantly associated with genitourinary defects (P = 6.08×10(-12. The causality of defects observed in 5p15.3, 9p24.3, 22q12.1 and Xq28 was supported by the presence of overlapping chromosomal rearrangements in several unrelated patients. In addition to known gonad determining genes including SRY and DMRT1, novel candidate genes such as FGFR2, KANK1, ADCY2 and ZEB2 were encompassed. The identification of risk germline rearrangements for urogenital birth defects may impact diagnosis and genetic counseling and contribute to the elucidation of the molecular mechanisms underlying the pathogenesis of human sexual development.

  18. Cost-effective treatment of low-risk carcinoma not invading bladder muscle.

    Science.gov (United States)

    Green, David A; Rink, Michael; Cha, Eugene K; Xylinas, Evanguelos; Chughtai, Bilal; Scherr, Douglas S; Shariat, Shahrokh F; Lee, Richard K

    2013-03-01

    Study Type - Therapy (cost effectiveness analysis) Level of Evidence 2a What's known on the subject? and What does the study add? Bladder cancer is one of the costliest malignancies to treat throughout the life of a patient. The most cost-effective management for low-risk non-muscle-invasive bladder cancer is not known. The current study shows that employing cystoscopic office fulguration for low-risk appearing bladder cancer recurrences can materially impact the cost-effectiveness of therapy. In a follow-up protocol where office fulguration is routinely employed for low-risk bladder cancers, peri-operative intravesical chemotherapy may not provide any additional cost-effectiveness benefit. To examine the cost-effectiveness of fulguration vs transurethral resection of bladder tumour (TURBT) with and without perioperative intravesical chemotherapy (PIC) for managing low-risk carcinoma not invading bladder muscle (NMIBC). Low-risk NMIBC carries a low progression rate, lending support to the use of office-based fulguration for small recurrences rather than traditional TURBT. A Markov state transition model was created to simulate treatment of NMIBC with vs without PIC, with recurrence treated by formal TURBT vs treatment with fulguration. Costing data were obtained from the Medicare Resource Based Relative Value Scale. Data regarding the success of PIC were obtained from the peer-reviewed literature, as were corresponding utilities for bladder cancer-related procedures. Sensitivity analyses were performed. At 5-year follow-up, a strategy of fulguration without PIC was the most cost-effective (mean cost-effectiveness = US $654.8/quality-adjusted life year), despite a lower recurrence rate with PIC. Both fulguration strategies dominated each TURBT strategy. Sensitivity analysis showed that fulguration without PIC dominated all other strategies when the recurrence rate after PIC was increased to ≥14.2% per year. Similarly, the cost-effectiveness of TURBT becomes more

  19. Characteristics of high- and low-risk individuals in the PRIORITY study

    DEFF Research Database (Denmark)

    Tofte, N; Lindhardt, M; Adamova, K

    2018-01-01

    variable. In a logistic regression model including clinical variables known to be associated with diabetic kidney disease, estimated GFR, gender, log urinary albumin:creatinine ratio and use of renin-angiotensin system-blocking agents remained significant determinants of the CKD273 high-risk group: area......AIM: To compare clinical baseline data in individuals with Type 2 diabetes and normoalbuminuria, who are at high or low risk of diabetic kidney disease based on the urinary proteomics classifier CKD273. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled international...... multicentre clinical trial and observational study in participants with Type 2 diabetes and normoalbuminuria, stratified into high- or low-risk groups based on CKD273 score. Clinical baseline data for the whole cohort and stratified by risk groups are reported. The associations between CKD273 and traditional...

  20. Do Ontarians drink in moderation? a baseline assessment against Canadian low risk drinking guidelines.

    Science.gov (United States)

    Bondy, S J; Ashley, M J; Rehm, J T; Walsh, G

    1999-01-01

    We used the 1997 Ontario Drug Monitor, a population-based, random-digit dialing survey of 2,776 adults, to obtain a baseline assessment of alcohol drinking by Ontarians against the 1997 low-risk drinking guidelines of the Addiction Research Foundation and the Canadian Centre on Substance Abuse. Average weekly alcohol consumption and the frequency of exceeding the daily limit, estimated using the graduated frequency scale, were determined for the population overall, and by sex and age group (18-44 and 45+ years). Most Ontarians drank alcohol in a pattern associated with a low risk of health consequences. About 10% of women and 25% of men drank in a style associated with some increase in acute or long-term risk. Younger men were most likely to drink in a risky pattern. Most drinkers of middle age or older, for whom cardiovascular disease is a significant health risk, consumed alcohol in a pattern associated with cardiovascular benefit.

  1. Predictive value of late decelerations for fetal acidemia in unselective low-risk pregnancies.

    Science.gov (United States)

    Sameshima, Hiroshi; Ikenoue, Tsuyomu

    2005-01-01

    We evaluated the clinical significance of late decelerations (LD) of intrapartum fetal heart rate (FHR) monitoring to detect low pH (LD (occasional, 50%; recurrent, > or = 50%) and severity (reduced baseline FHR accelerations and variability) of LD, and low pH (test, and one-way analysis of variance with the Bonferroni/Dunn test. In the 5522 low-risk pregnancies, 301 showed occasional LD and 99 showed recurrent LD. Blood gases and pH values deteriorated as the incidence of LD increased and as baseline accelerations or variability was decreased. Positive predictive value for low pH (LD, and > 50% in recurrent LD with no baseline FHR accelerations and reduced variability. In low-risk pregnancies, information on LD combined with acceleration and baseline variability enables us to predict the potential incidence of fetal acidemia.

  2. Willingness to pay for a cure of low-risk melanoma patients in Germany.

    Science.gov (United States)

    Augustin, Matthias; Blome, Christine; Forschner, Andrea; Gutzmer, Ralf; Hauschild, Axel; Heinzerling, Lucie; Livingstone, Elisabeth; Loquai, Carmen; Schadendorf, Dirk; Utikal, Jochen; Wagner, Tobias; Wilden, Sophia; Kähler, Katharina C

    2018-01-01

    Malignant melanoma is potentially life-threatening but in most cases curable if detected early. Willingness to pay (WTP) is a preference-based construct that reflects burden of disease by assessment of the monetary value for a hypothetical cure from disease. Since WTP (directly as total amount of money) has not been assessed so far in patients with low risk melanoma, it was interesting to gain insights in this patient population and then, in a second step, compare it directly with the WTP of their treating dermato-oncologists. WTP was assessed in 125 patients with low-risk melanoma and additionally in 105 treating physicians, asking for the one-time and continuous payments they would be willing to make for a sustainable cure, both as absolute sums and as percentages of monthly income. The median WTP based on one-time payment was €10,000 for patients and €100,000 for physicians; relative numbers were 100% versus 300% of monthly income. For continuous monthly payments, WTP was €500 for patients and €1000 for physicians, relative numbers 25% and 50% of income, respectively. Even after controlling for income differences, there was a significantly higher WTP in physicians for all four questions. Compared to patients with chronic skin diseases such as vitiligo, rosacea, atopic eczema and psoriasis, patients with low-risk melanoma showed a significantly higher WTP. Our data suggest that there is a relevant burden of disease even in patients with low-risk tumors. Higher WTP of physicians underlines the prevalence of differences in disease perception.

  3. Allergy Testing in Children With Low-Risk Penicillin Allergy Symptoms.

    Science.gov (United States)

    Vyles, David; Adams, Juan; Chiu, Asriani; Simpson, Pippa; Nimmer, Mark; Brousseau, David C

    2017-08-01

    Penicillin allergy is commonly reported in the pediatric emergency department (ED). True penicillin allergy is rare, yet the diagnosis results from the denial of first-line antibiotics. We hypothesize that all children presenting to the pediatric ED with symptoms deemed to be low-risk for immunoglobulin E-mediated hypersensitivity will return negative results for true penicillin allergy. Parents of children aged 4 to 18 years old presenting to the pediatric ED with a history of parent-reported penicillin allergy completed an allergy questionnaire. A prespecified 100 children categorized as low-risk on the basis of reported symptoms completed penicillin allergy testing by using a standard 3-tier testing process. The percent of children with negative allergy testing results was calculated with a 95% confidence interval. Five hundred ninety-seven parents completed the questionnaire describing their child's reported allergy symptoms. Three hundred two (51%) children had low-risk symptoms and were eligible for testing. Of those, 100 children were tested for penicillin allergy. The median (interquartile range) age at testing was 9 years (5-12). The median (interquartile range) age at allergy diagnosis was 1 year (9 months-3 years). Rash (97 [97%]) and itching (63 [63%]) were the most commonly reported allergy symptoms. Overall, 100 children (100%; 95% confidence interval 96.4%-100%) were found to have negative results for penicillin allergy and had their labeled penicillin allergy removed from their medical record. All children categorized as low-risk by our penicillin allergy questionnaire were found to have negative results for true penicillin allergy. The utilization of this questionnaire in the pediatric ED may facilitate increased use of first-line penicillin antibiotics. Copyright © 2017 by the American Academy of Pediatrics.

  4. First-line chemotherapy in low-risk gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-01-01

    This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.

  5. Spirituality and low-risk consumption of alcohol in young adults

    OpenAIRE

    Díaz Heredia, Luz Patricia; Muñoz Sánchez, Alba Idaly

    2013-01-01

    The relationship between spirituality and health, as well as it effect on adopting healthy behaviors, is a topic of interest for nursing and, in general, for social and life sciences. Spirituality, as a human realm, is a relevant research theme that is often related to the promotion of health in individuals. Studies indicate that spirituality is related to mental and physical health, being a protective and promoting factor of healthy behaviors, among them low-risk consumption of alcohol in yo...

  6. Image-Guided Hypofractionated Radiotherapy in Low-Risk Prostate Cancer Patients

    Directory of Open Access Journals (Sweden)

    Maurizio Valeriani

    2014-01-01

    Full Text Available Aim. To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT. Methods. Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions. Results. The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI and genitourinary (GU toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower (P=0.04 in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher (P<0.001 for HFRT patients. Conclusions. Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT.

  7. Visual performance in preterm infants with brain injuries compared with low-risk preterm infants.

    Science.gov (United States)

    Leonhardt, Merçè; Forns, Maria; Calderón, Caterina; Reinoso, Marta; Gargallo, Estrella

    2012-08-01

    Neonatal brain injuries are the main cause of visual deficit produced by damage to posterior visual pathways. While there are several studies of visual function in low-risk preterm infants or older children with brain injuries, research in children of early age is lacking. To assess several aspects of visual function in preterm infants with brain injuries and to compare them with another group of low-risk preterm infants of the same age. Forty-eight preterm infants with brain injuries and 56 low-risk preterm infants. The ML Leonhardt Battery of Optotypes was used to assess visual functions. This test was previously validated at a post-menstrual age of 40 weeks in newborns and at 30-plus weeks in preterm infants. The group of preterm infants with brain lesions showed a delayed pattern of visual functions in alertness, fixation, visual attention and tracking behavior compared to infants in the healthy preterm group. The differences between both groups, in the visual behaviors analyzed were around 30%. These visual functions could be identified from the first weeks of life. Our results confirm the importance of using a straightforward screening test with preterm infants in order to assess altered visual function, especially in infants with brain injuries. The findings also highlight the need to provide visual stimulation very early on in life. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Governmental standard drink definitions and low-risk alcohol consumption guidelines in 37 countries.

    Science.gov (United States)

    Kalinowski, Agnieszka; Humphreys, Keith

    2016-07-01

    One of the challenges of international alcohol research and policy is the variability in and lack of knowledge of how governments in different nations define a standard drink and low-risk drinking. This study gathered such information from governmental agencies in 37 countries. A pool of 75 countries that might have definitions was created using World Health Organization (WHO) information and the authors' own judgement. Structured internet searches of relevant terms for each country were supplemented by efforts to contact government agencies directly and to consult with alcohol experts in the country. Most of the 75 national governments examined were not identified as having adopted a standard drink definition. Among the 37 that were so identified, the modal standard drink size was 10 g pure ethanol, but variation was wide (8-20 g). Significant variability was also evident for low-risk drinking guidelines, ranging from 10-42 g per day for women and 10-56 g per day for men to 98-140 g per week for women and 150-280 g per week for men. Researchers working and communicating across national boundaries should be sensitive to the substantial variability in 'standard' drink definitions and low-risk drinking guidelines. The potential impact of guidelines, both in general and in specific national cases, remains an important question for public health research. © 2016 Society for the Study of Addiction.

  9. [Clinical guideline for management of patients with low risk differentiated thyroid carcinoma].

    Science.gov (United States)

    Díez, Juan José; Oleaga, Amelia; Álvarez-Escolá, Cristina; Martín, Tomás; Galofré, Juan Carlos

    2015-01-01

    Incidence of thyroid cancer is increasing in Spain and worldwide. Overall thyroid cancer survival is very high, and stratification systems to reliably identify patients with worse prognosis have been developed. However, marked differences exist between the different specialists in clinical management of low-risk patients with thyroid carcinoma. Almost half of all papillary thyroid carcinomas are microcarcinomas, and 90% are tumors < 2 cm that have a particularly good prognosis. However, they are usually treated more aggressively than needed, despite the lack of adequate scientific support. Surgery remains the gold standard treatment for these tumors. However, lobectomy may be adequate in most patients, without the need for total thyroidectomy. Similarly, prophylactic lymph node dissection of the central compartment is not required in most cases. This more conservative approach prevents postoperative complications such as hypoparathyroidism or recurrent laryngeal nerve injury. Postoperative radioiodine remnant ablation and strict suppression of serum thyrotropin, although effective for the more aggressive forms of thyroid cancer, have not been shown to be beneficial for the treatment of low risk patients, and may impair their quality of life. This guideline provides recommendations from the task force on thyroid cancer of the Spanish Society of Endocrinology and Nutrition for adequate management of patients with low-risk thyroid cancer. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  10. [Postoperative radioiodine ablation in patients with low risk differentiated thyroid carcinoma].

    Science.gov (United States)

    Díez, Juan J; Grande, Enrique; Iglesias, Pedro

    2015-01-06

    Most patients with newly diagnosed differentiated thyroid carcinoma have tumors with low risk of mortality and recurrence. Standard therapy has been total or near total thyroidectomy followed by postoperative radioiodine remnant ablation (RRA). Although RRA provides benefits, current clinical guidelines do not recommend it universally, since an increase in disease-free survival or a decrease in mortality in low risk patients has not been demonstrated so far. Advancements in our understanding of the biological behavior of thyroid cancer have been translated into the clinic in a personalized approach to the patients based on their individual risk of recurrence and mortality. Current evidence suggests that RRA is not indicated in most low-risk patients, especially those with papillary carcinomas smaller than 1cm, without extrathyroidal extension, unfavorable histology, lymph node involvement or distant metastases. Follow-up of these patients with serial measurements of serum thyroglobulin and neck ultrasound is adequate. Careful evaluation of all risk factors of clinical relevance will allow a more realistic assessment of each individual patient. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  11. Perinatal mortality and morbidity in a nationwide cohort of 529,688 low-risk planned home and hospital births

    NARCIS (Netherlands)

    de jonge, A.; van der Goes, B. Y.; Ravelli, A. C. J.; Amelink-Verburg, M. P.; Mol, B. W.; Nijhuis, J. G.; Bennebroek Gravenhorst, J.; Buitendijk, S. E.

    2009-01-01

    OBJECTIVE: To compare perinatal mortality and severe perinatal morbidity between planned home and planned hospital births, among low-risk women who started their labour in primary care. DESIGN: A nationwide cohort study. SETTING: The entire Netherlands. POPULATION: A total of 529,688 low-risk women

  12. Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH.

    Science.gov (United States)

    Meijers, Wouter C; de Boer, Rudolf A; van Veldhuisen, Dirk J; Jaarsma, Tiny; Hillege, Hans L; Maisel, Alan S; Di Somma, Salvatore; Voors, Adriaan A; Peacock, W Frank

    2015-12-01

    Traditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization. This analysis was a substudy of The Coordinating Study Evaluating Outcomes of Advising and Counselling in Heart Failure (COACH) trial. Enrolment of HF patients occurred before discharge. We defined low risk as the absence of death and/or HF rehospitalizations at 180 days. We tested a diverse group of 29 biomarkers on top of a clinical risk model, with and without N-terminal pro-B-type natriuretic peptide (NT-proBNP), and defined the low risk biomarker cut-off at the 10th percentile associated with high positive predictive value. The best performing biomarkers together with NT-proBNP and cardiac troponin I (cTnI) were re-evaluated in a validation cohort of 285 HF patients. Of 592 eligible COACH patients, the mean (± SD) age was 71 (± 11) years and median (IQR) NT-proBNP was 2521 (1301-5634) pg/mL. Logistic regression analysis showed that only galectin-3, fully adjusted, was significantly associated with the absence of events at 180 days (OR 8.1, 95% confidence interval 1.06-50.0, P = 0.039). Galectin-3, showed incremental value when added to the clinical risk model without NT-proBNP (increase in area under the curve from 0.712 to 0.745, P = 0.04). However, no biomarker showed significant improvement by net reclassification improvement on top of the clinical risk model, with or without NT-proBNP. We confirmed our results regarding galectin-3, NT-proBNP, and cTnI in the independent validation cohort. We describe the value of various biomarkers to define low risk, and demonstrate that galectin-3 identifies HF patients at (very) low risk for 30-day and 180-day mortality and HF rehospitalizations after an episode of acute HF. Such patients might be safely discharged. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of

  13. Use of advanced treatment technologies among men at low risk of dying from prostate cancer.

    Science.gov (United States)

    Jacobs, Bruce L; Zhang, Yun; Schroeck, Florian R; Skolarus, Ted A; Wei, John T; Montie, James E; Gilbert, Scott M; Strope, Seth A; Dunn, Rodney L; Miller, David C; Hollenbeck, Brent K

    2013-06-26

    The use of advanced treatment technologies (ie, intensity-modulated radiotherapy [IMRT] and robotic prostatectomy) for prostate cancer is increasing. The extent to which these advanced treatment technologies have disseminated among patients at low risk of dying from prostate cancer is uncertain. To assess the use of advanced treatment technologies, compared with prior standards (ie, traditional external beam radiation treatment [EBRT] and open radical prostatectomy) and observation, among men with a low risk of dying from prostate cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified a retrospective cohort of men diagnosed with prostate cancer between 2004 and 2009 who underwent IMRT (n = 23,633), EBRT (n = 3926), robotic prostatectomy (n = 5881), open radical prostatectomy (n = 6123), or observation (n = 16,384). Follow-up data were available through December 31, 2010. The use of advanced treatment technologies among men unlikely to die from prostate cancer, as assessed by low-risk disease (clinical stage ≤T2a, biopsy Gleason score ≤6, and prostate-specific antigen level ≤10 ng/mL), high risk of noncancer mortality (based on the predicted probability of death within 10 years in the absence of a cancer diagnosis), or both. In our cohort, the use of advanced treatment technologies increased from 32% (95% CI, 30%-33%) to 44% (95% CI, 43%-46%) among men with low-risk disease (P risk of noncancer mortality (P use of these advanced treatment technologies among men with both low-risk disease and high risk of noncancer mortality increased from 25% (95% CI, 23%-28%) to 34% (95% CI, 31%-37%) (P use of advanced treatment technologies for men unlikely to die from prostate cancer increased from 13% (95% CI, 12%-14%), or 129.2 per 1000 patients diagnosed with prostate cancer, to 24% (95% CI, 24%-25%), or 244.2 per 1000 patients diagnosed with prostate cancer (P risk disease, high risk of noncancer mortality, or both, the use of

  14. National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, David D. [Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Medicine, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Labe, Shelby A.; Nezolosky, Michelle D.; Vastola, Marie E.; King, Martin T.; Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Choueiri, Toni K. [Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Trinh, Quoc-Dien [Division of Urological Surgery, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Spratt, Daniel E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); University of Michigan, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Feng, Felix Y. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Departments of Urology & Medicine and Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California (United States); and others

    2017-06-01

    Purpose: Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Methods and Materials: Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level <10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Results: Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P<.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P<.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P<.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P<.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P<.001) after adjustment for age and comorbidity. Conclusions: ADT use in low-risk prostate cancer has declined nationally but may remain an issue

  15. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  16. A pharmacoeconomic analysis of the use of single MMC instillation in low risk NMIBC in Italy

    Directory of Open Access Journals (Sweden)

    Renzo Colombo

    2013-03-01

    Full Text Available BACKGROUND: Bladder cancer accounts for 5-10% of all cancers in Europe and up to 85% patients presents a noninvasive tumor, whose treatment of choice is the transurethral bladder resection (TURB paired with adjuvant intravesical chemotherapy or immunotherapy. Despite several clinical trials showed that this treatment is safe and decreases recurrences by 17% to 44% this practice is limited for many reasons. The study objective is to analyze the economical advantages of the single immediate post operative Mitomycin C instillation in Non Muscle-invasive Bladder Cancer (NMIBC low-risk patients.METHODS: A cost-benefit analysis was performed evaluating the economical gain that would raised from a scenario with a single immediate post operative mitomycin C instillation in each low-risk NMIBC patient who underwent to TURB. Net present value and cost-benefit ratio were calculated and sensitivity analyses were performed. Base case analysis was performed considering tumor recurrence rate reduction of 11.7% and a TURB costs of 2,167.0 €, while sensitivity analyses were performed using a recurrence rate reduction of 19.2% and 15.0% and a TURB cost of 2,472.93 €. The discount rate was 2%.RESULTS: The single immediate post operative instillation of mitomycin C resulted to be cost-beneficial with a cost-benefit ratio that goes from 0.48 to 0.79 when compared to TURB alone raising a Net Present Value that goes from 660,284.39 € to 2,650,530.79 €.CONCLUSION: This study demonstrates that even assuming conservative parameters for recurrence rates reduction, a single immediate post operative mitomycin C instillation in low risk NMIBC patients would lower not only the recurrence rate but also the caring cost for bladder cancer.

  17. Unilateral Prostate Cancer Cannot be Accurately Predicted in Low-Risk Patients

    International Nuclear Information System (INIS)

    Isbarn, Hendrik; Karakiewicz, Pierre I.; Vogel, Susanne

    2010-01-01

    Purpose: Hemiablative therapy (HAT) is increasing in popularity for treatment of patients with low-risk prostate cancer (PCa). The validity of this therapeutic modality, which exclusively treats PCa within a single prostate lobe, rests on accurate staging. We tested the accuracy of unilaterally unremarkable biopsy findings in cases of low-risk PCa patients who are potential candidates for HAT. Methods and Materials: The study population consisted of 243 men with clinical stage ≤T2a, a prostate-specific antigen (PSA) concentration of <10 ng/ml, a biopsy-proven Gleason sum of ≤6, and a maximum of 2 ipsilateral positive biopsy results out of 10 or more cores. All men underwent a radical prostatectomy, and pathology stage was used as the gold standard. Univariable and multivariable logistic regression models were tested for significant predictors of unilateral, organ-confined PCa. These predictors consisted of PSA, %fPSA (defined as the quotient of free [uncomplexed] PSA divided by the total PSA), clinical stage (T2a vs. T1c), gland volume, and number of positive biopsy cores (2 vs. 1). Results: Despite unilateral stage at biopsy, bilateral or even non-organ-confined PCa was reported in 64% of all patients. In multivariable analyses, no variable could clearly and independently predict the presence of unilateral PCa. This was reflected in an overall accuracy of 58% (95% confidence interval, 50.6-65.8%). Conclusions: Two-thirds of patients with unilateral low-risk PCa, confirmed by clinical stage and biopsy findings, have bilateral or non-organ-confined PCa at radical prostatectomy. This alarming finding questions the safety and validity of HAT.

  18. Preferred place of birth: characteristics and motives of low-risk nulliparous women in the Netherlands.

    Science.gov (United States)

    van Haaren-Ten Haken, Tamar; Hendrix, Marijke; Nieuwenhuijze, Marianne; Budé, Luc; de Vries, Raymond; Nijhuis, Jan

    2012-10-01

    to explores preferences, characteristics and motives regarding place of birth of low-risk nulliparous women in the Netherlands. a prospective cohort study of low-risk nulliparous women and their partners starting their pregnancy in midwifery-led care or in obstetric-led care. Data were collected using a self-administered questionnaire, including questions on demographic, psychosocial and pregnancy factors and statements about motives with regard to place of birth. Depression, worry and self-esteem were explored using the Edinburgh Depression Scale (EDS), the Cambridge Worry Scale (CWS) and the Rosenberg Self Esteem Scale (RSE). participants were recruited in 100 independent midwifery practices and 14 hospitals from 2007 to 2011. 550 low-risk nulliparous women; 231 women preferred a home birth, 170 women a hospital birth in midwifery-led care and 149 women a birth in obstetric-led care. Significant differences in characteristics were found in the group who preferred a birth in obstetric-led care compared to the two groups who preferred midwifery-led care. Those women were older (F (2,551)=16.14, pbirth is driven by a desire for greater personal autonomy, whereas women's choice for a hospital birth is driven by a desire to feel safe and control risks. the characteristics of women who prefer a hospital birth are different than the characteristics of women who prefer a home birth. It appears that for women preferring a hospital birth, the assumed safety of the hospital is more important than type of care provider. This brings up the question whether women are fully aware of the possibilities of maternity care services. Women might need concrete information about the availability and the characteristics of the services within the maternity care system and the risks and benefits associated with either setting, in order to make an informed choice where to give birth. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Perioperative pulmonary aspiration is infrequent and low risk in pediatric anesthetic practice.

    Science.gov (United States)

    Kelly, Christopher J; Walker, Robert W M

    2015-01-01

    Recent studies have reported perioperative pulmonary aspiration in pediatric practice to be an uncommon problem associated with low morbidity and mortality. This paper examines the recent publications in both the adult and pediatric literature and looks at some of the potential risk factors involved, both patient and anesthetic, in the development of aspiration of gastric contents. We also look at the risk of severe morbidity following pulmonary aspiration and speculate on possible reasons behind the assertion that pulmonary aspiration in pediatric anesthetic practice is rare and a low-risk event. © 2014 John Wiley & Sons Ltd.

  20. A case series of Nasopharyngeal Carcinoma among Indians, a low risk population, in Perak State, Malaysia.

    Science.gov (United States)

    Anusha, B; Philip, R; Norain, K; Harvinder, S; Gurdeep, S M

    2012-12-01

    Nasopharyngeal carcinoma (NPC) is rare among people of Indian ethnicity. A short retrospective case review of clinical records of Indian patients diagnosed with nasopharyngeal carcinoma in a period of 5 years was conducted. Their slides were further subjected to EBV encoded RNA (EBER) - In- situ Hybridization (ISH). The histologic subtype was nonkeratinizing carcinoma in all 4 patients. All were Epstein Barr Virus (EBV) positive. We believe that the crucial factor responsible for nasopharyngeal carcinoma is genetics; either a genetic susceptibility among high risk groups or genetic resistance/immunity in low risk groups. Further genetic studies are required to look for somatic or inherited chromosomal mutations among the various risk populations.

  1. Clinically low-risk prostate cancer: evaluation with transrectal doppler ultrasound and functional magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Maria Inês Novis

    2011-01-01

    Full Text Available OBJECTIVES: To evaluate transrectal ultrasound, amplitude Doppler ultrasound, conventional T2-weighted magnetic resonance imaging, spectroscopy and dynamic contrast-enhanced magnetic resonance imaging in localizing and locally staging low-risk prostate cancer. INTRODUCTION: Prostate cancer has been diagnosed at earlier stages and the most accepted classification for low-risk prostate cancer is based on clinical stage T1c or T2a, Gleason score <6, and prostate-specific antigen (PSA <10 ng/ml. METHODS: From 2005 to 2006, magnetic resonance imaging was performed in 42 patients, and transrectal ultrasound in 26 of these patients. Seven patients were excluded from the study. Mean patient age was 64.94 years and mean serum PSA was 6.05 ng/ml. The examinations were analyzed for tumor identification and location in prostate sextants, detection of extracapsular extension, and seminal vesicle invasion, using surgical pathology findings as the gold standard. RESULTS: Sixteen patients (45.7% had pathologically proven organ-confined disease, 11 (31.4% had positive surgical margin, 8 (28.9% had extracapsular extension, and 3 (8.6% presented with extracapsular extension and seminal vesicle invasion. Sensitivity, specificity, positive predictive value (PPV, negative predictive value (NPV and accuracy values for localizing low-risk prostate cancer were 53.1%, 48.3%, 63.4%, 37.8% and 51.3% for transrectal ultrasound; 70.4%, 36.2%, 65.1%, 42.0% and 57.7% for amplitude Doppler ultrasound; 71.5%, 58.9%, 76.6%, 52.4% and 67.1% for magnetic resonance imaging; 70.4%, 58.7%, 78.4%, 48.2% and 66.7% for magnetic resonance spectroscopy; 67.2%, 65.7%, 79.3%, 50.6% and 66.7% for dynamic contrast-enhanced magnetic resonance imaging, respectively. Sensitivity, specificity, PPV, NPV and accuracy values for detecting extracapsular extension were 33.3%, 92%, 14.3%, 97.2% and 89.7% for transrectal ultrasound and 50.0%, 77.6%, 13.7%, 95.6% and 75.7% for magnetic resonance imaging

  2. Variants of glycoside hydrolases

    Science.gov (United States)

    Teter, Sarah [Davis, CA; Ward, Connie [Hamilton, MT; Cherry, Joel [Davis, CA; Jones, Aubrey [Davis, CA; Harris, Paul [Carnation, WA; Yi, Jung [Sacramento, CA

    2011-04-26

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  3. Factors Associated With Mortality in Low-Risk Pediatric Critical Care Patients in The Netherlands.

    Science.gov (United States)

    Verlaat, Carin W; Visser, Idse H; Wubben, Nina; Hazelzet, Jan A; Lemson, Joris; van Waardenburg, Dick; van der Heide, Douwe; van Dam, Nicolette A; Jansen, Nicolaas J; van Heerde, Mark; van der Starre, Cynthia; van Asperen, Roelie; Kneyber, Martin; van Woensel, Job B; van den Boogaard, Mark; van der Hoeven, Johannes

    2017-04-01

    To determine differences between survivors and nonsurvivors and factors associated with mortality in pediatric intensive care patients with low risk of mortality. Retrospective cohort study. Patients were selected from a national database including all admissions to the PICUs in The Netherlands between 2006 and 2012. Patients less than 18 years old admitted to the PICU with a predicted mortality risk lower than 1% according to either the recalibrated Pediatric Risk of Mortality or the Pediatric Index of Mortality 2 were included. None. In total, 16,874 low-risk admissions were included of which 86 patients (0.5%) died. Nonsurvivors had more unplanned admissions (74.4% vs 38.5%; p < 0.001), had more complex chronic conditions (76.7% vs 58.8%; p = 0.001), were more often mechanically ventilated (88.1% vs 34.9%; p < 0.001), and had a longer length of stay (median, 11 [interquartile range, 5-32] d vs median, 3 [interquartile range, 2-5] d; p < 0.001) when compared with survivors. Factors significantly associated with mortality were complex chronic conditions (odds ratio, 3.29; 95% CI, 1.97-5.50), unplanned admissions (odds ratio, 5.78; 95% CI, 3.40-9.81), and admissions in spring/summer (odds ratio, 1.67; 95% CI, 1.08-2.58). Nonsurvivors in the PICU with a low predicted mortality risk have recognizable risk factors including complex chronic condition and unplanned admissions.

  4. Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes

    Directory of Open Access Journals (Sweden)

    King Christopher R

    2011-01-01

    Full Text Available Abstract Purpose Hypofractionated, stereotactic body radiotherapy (SBRT is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT. Method and Materials Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method and RTOG toxicity outcomes were assessed. Results At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%. Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation. Conclusion Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.

  5. Foot length measurements of newborns of high and low risk pregnancies

    Directory of Open Access Journals (Sweden)

    Ana Karina Marques Salge

    Full Text Available Abstract OBJECTIVE Comparing foot length measurements of newborns in high and low risk pregnancies at a public hospital in Goiânia, GO, Brazil. METHOD A cross-sectional study carried out between April, 2013 and May, 2015, with a sample consisting of 180 newborns; 106 infants of women from high-risk pregnancies and 74 of women from low-risk pregnancies. Data were descriptively analyzed. Foot length measurement was performed using a stiff transparent plastic ruler, graduated in millimeters. The length of both feet was measured from the tip of the hallux (big toe to the end of the heel. RESULTS A statistically significant relationship was found between the foot length and newborn’s weight, between the cephalic and thoracic perimeters in the high-risk group and between the cephalic perimeter in the control group. CONCLUSION There is a need for creating cut-off points to identify newborns with intrauterine growth disorders using foot length.

  6. Milk intake is not associated with low risk of diabetes or overweight-obesity

    DEFF Research Database (Denmark)

    Bergholdt, Helle K M; Nordestgaard, Børge G; Ellervik, Christina

    2015-01-01

    BACKGROUND: High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown. OBJECTIVE: We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obesity......, observationally and genetically. DESIGN: In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype [polymorphism (rs4988235) upstream from the lactase (LCT) gene], where TT...... and TC genotypes are associated with lactase persistence and CC with nonpersistence. RESULTS: Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk...

  7. Vaginal flora alterations and clinical symptoms in low-risk pregnant women.

    Science.gov (United States)

    Gondo, Fausto; da Silva, Márcia G; Polettini, Jossimara; Tristao, Andréa da R; Peracoli, José C; Witkin, Steven S; Rudge, Marilza V C

    2011-01-01

    To evaluate associations between alterations in vaginal flora and clinical symptoms in low-risk pregnant women. Vaginal specimens from 245 pregnant women were analyzed by microscopy for vaginal flora. Signs and symptoms of vaginal infection were determined by patient interviews and gynecologic examinations. Abnormal vaginal flora was identified in 45.7% of the subjects. The final clinical diagnoses were bacterial vaginosis (21.6%), vaginal candidosis (10.2%), intermediate vaginal flora (5.2%), aerobic vaginitis (2.9%), mixed flora (2.9%) and other abnormal findings (2.9%). The percentage of women with or without clinical signs or symptoms was not significantly different between these categories. The presence of vaginal odor or vaginal discharge characteristics was not diagnostic of any specific flora alteration; pruritus was highly associated with candidosis (p vaginal odor was associated with bacterial vaginosis (p = 0.0026). The prevalence of atypical vaginal flora is common in our low-risk pregnant population and is not always associated with pathology. The occurrence of specific signs or symptoms does not always discriminate between women with different types of atypical vaginal flora or between those with abnormal and normal vaginal flora. Copyright © 2010 S. Karger AG, Basel.

  8. Ureteral diameter in low-risk vesicoureteral reflux in infancy and childhood

    International Nuclear Information System (INIS)

    Hellstroem, M.; Hjaelmaas, K.; Jacobsson, B.; Jodal, U.; Oestra Sjukhuset, Goeteborg; Oestra Sjukhuset, Goeteborg

    1986-01-01

    In order to improve the accuracy of the grading of vesicoureteral reflux (VUR), reference values for ureteral diameter at micturition cystourethrography (MCUG) were established in infants and children with low-risk VUR. Low-risk VUR was defined as VUR not associated with infection, obstruction, calculi, duplication, malformations (except for hypospadia) or neurogenic bladder disturbances. Forty-six children (age 1 day - 14 years) were selected by examining the records of 12000 MCUG:s performed 1960-1983. Ureteral diameter was measured at the widest point of the ureter on the films from MCUG:s and urographies. Ureteral diameter was slightly larger at MCUG than at urography in the same individuals but the difference was not significant. The ureteral diameter at MCUG also correlated closely to normal values at urography in a previous study. It is proposed that the reference values obtained at MCUG in the present investigation can be used for the differentiation between dilatation and no dilatation in the grading of VUR. (orig.)

  9. The role of genetic breast cancer susceptibility variants as prognostic factors

    DEFF Research Database (Denmark)

    Fasching, Peter A; Pharoah, Paul D P; Cox, Angela

    2012-01-01

    Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8...

  10. High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

    2014-01-01

    OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid......-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up...... cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types. LEVEL OF EVIDENCE: II....

  11. Trichomonas vaginalis infection in a low-risk women attended in Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre

    Directory of Open Access Journals (Sweden)

    Norhayati Moktar

    2016-08-01

    Conclusions: The present study reported zero incidence rate of trichomoniasis. The low incidence rate was postulated due to all women who participated in this study were categorized into a low-risk group.

  12. Accurate genotyping across variant classes and lengths using variant graphs

    DEFF Research Database (Denmark)

    Sibbesen, Jonas Andreas; Maretty, Lasse; Jensen, Jacob Malte

    2018-01-01

    of read k-mers to a graph representation of the reference and variants to efficiently perform unbiased, probabilistic genotyping across the variation spectrum. We demonstrate that BayesTyper generally provides superior variant sensitivity and genotyping accuracy relative to existing methods when used...... collecting a set of candidate variants across discovery methods, individuals and databases, and then realigning the reads to the variants and reference simultaneously. However, this realignment problem has proved computationally difficult. Here, we present a new method (BayesTyper) that uses exact alignment...... to integrate variants across discovery approaches and individuals. Finally, we demonstrate that including a ‘variation-prior’ database containing already known variants significantly improves sensitivity....

  13. A Systematic Approach to Discussing Active Surveillance with Patients with Low-risk Prostate Cancer.

    Science.gov (United States)

    Ehdaie, Behfar; Assel, Melissa; Benfante, Nicole; Malhotra, Deepak; Vickers, Andrew

    2017-06-01

    Physicians report difficulty convincing patients with prostate cancer about the merits of active surveillance (AS); as a result, a majority of patients unnecessarily choose to undergo radical treatment. To develop and evaluate a systematic approach for physicians to counsel patients with low-risk prostate cancer to increase acceptance of AS. A systematic counseling approach was developed and piloted in one clinic. Then five surgeons participated in a 1-h training session in which they learned about the approach. A total of 1003 patients with Gleason 3+3 prostate cancer were included in the study. We compared AS rates for 761 patients who were counseled over a 24-mo period before the training intervention with AS rates for 242 patients who were counseled over a 12-mo period afterwards, controlling for temporal trends and case mix. A systematic approach for communicating the merits of AS using appropriate framing techniques derived from principles studied by negotiation scholars. The rate of AS acceptance by patients for management of low-risk prostate cancer. In the pilot phase, 81 of 86 patients (94%) accepted AS after counseling by the physician who developed the counseling approach. In the subsequent study, the cohort for the training intervention comprised 1003 consecutive patients, 80% of whom met the Epstein criteria for very low-risk disease. The proportion of patients who selected AS increased from 69% before the training intervention to 81% afterwards. After adjusting for time trends and case mix, the rate of AS after the intervention was 9.1% higher (95% confidence interval -0.4% to 19.4%) than expected, a relative reduction of approximately 30% in the risk of unnecessary curative treatment. A systematic approach to counseling can be taught to physicians in a 1-h lecture. We found evidence that even this minimal intervention can decrease overtreatment. Our novel approach offers a framework to help address cancer screening-related overtreatment that occurs

  14. [Draft of the best medical treatment in patients with low-risk thyroid cancer].

    Science.gov (United States)

    Vlček, Petr; Nováková, Dagmar; Vejvalka, Jan; Zimák, Jaroslav; Křenek, Martin; Vošmiková, Květuše; Smutný, Svatopluk; Bavor, Petr; Astl, Jaromír; Lukáš, Jindřich

    2015-09-01

    The incidence of well-differentiated low-risk thyroid cancer have increased globally over the last three decades. Thyroid cancer treatment relates to a suitable surgical procedure and the use of adjuvant radio-iodine therapy in selected patients. Evaluation of prognostic factors and risk stratification are critical for determining appropriate treatment. Survival of patients with low-risk thyroid cancer is excellent. Appropriate choice of medical treatment resulted in full recovery in most patients. Relapse risk increases with the size of the primary tumor, along with the findings of the risk factors in men. Our study included a total of 1 980 patients in whom were diagnosed T1a and T1b tumors between the years 2003 to 2012. The population included 1 675 women (84.6 %) of average age of 45.22 years and 305 men (15.4 %) of average age of 50.0 years. The bulk of the file represented papillary carcinomas (1 868; 94.4 %), and smaller group of follicular carcinomas (112; 5.6 %). Patients were divided into four groups according to tumor size. Patients were evaluated according to risk factors: unifocality no other risk factors, multifocality - more bearings in thyroid tumor, metastases in regional lymph nodes, distant metastases or combination of risk factors. Group A: In the monitored set of 678 patients with papillary and follicular microcarcinoma up to 5 mm, during histological input, the findings revealed one bearing (unifocal type of cancer) in 566 patients. Multifocality was found in 112 patients, local nodal metastasis were demonstrated in 24 cases and pulmonary metastasis was discove-red in 1 case. Group B: In this group there were 576 study patients with papillary and follicular microcarcinoma size of 5-10 mm. Histological findings were captured input one bearing carcinoma in 434 patients, 142 patients with multifocality, in 53 cases of local nodal metastasis, and 1 case of bone metastases. Group C: In this group there were 467 study patients with papillary

  15. Fear of childbirth and emergency caesarean section in low-risk nulliparous women

    DEFF Research Database (Denmark)

    Jespersen, Cecilie; Hegaard, Hanne Kristine; Schroll, Anne-Mette

    2014-01-01

    OBJECTIVE: To assess the association between fear of childbirth (FOC) and emergency caesarean section. DESIGN: A prospective cohort study of low-risk nulliparous women at term. SETTING: Nine obstetric departments in Denmark, May 2004-July 2005. POPULATION: A total of 2598 nulliparous women...... in spontaneous labor with a single fetus in cephalic presentation at term. METHODS: Self-reported FOC was assessed at 37 weeks of gestation by the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ) version A and at admission to the labor ward by the Delivery Fear Scale (DFS). Mode of delivery...... was recorded by the attending staff. Logistic regression analyses were used to estimate unadjusted and adjusted odds ratios (OR). MAIN OUTCOME MEASURES: Risk of emergency caesarean section in women who feared childbirth. RESULTS: FOC (W-DEQ sum score ≥ 85 and DFS sum score ≥ 70) was not associated...

  16. The selection of low-risk design guidelines for energetic events

    International Nuclear Information System (INIS)

    Fergusson, Donald; Marchaterre, John; Graham, John

    1982-01-01

    This paper recommends the establishment of specific design guidelines for protection against potential, but low probability, energetic events. These guidelines recognize the plant protective features incorporated to prevents such events, as well as the inherent capability of the plant to accommodate a certain level of energy release. Further, their application is recommended within the context of necessary standardized and agreed upon acceptance criteria which are less restrictive than ASME code requirements. The paper provides the background upon which the selection of the design is made, including the characterization of energetic events dependent on various core-design parameters, and including the necessity of a low-risk design balanced between prevention of accidents and the mitigation of consequences

  17. Providing reliable equipment to IAEA through a low risk transition plan

    International Nuclear Information System (INIS)

    Green, L.; Weinstock, E.V.; Karlin, E.W.

    1988-01-01

    The development and production of safeguards equipment is a complex process containing many potential pitfalls between the conceptual design and its implementation in the field. The conditions for equipment use are especially demanding. At the same time, the consequences of failure may be serious. Repeated failure may result in the loss of credibility of safeguards. Expensive back up measures such as re-verification of inventories may be required. Inspectors may come to distrust the equipment. Finally, the expense of maintaining the equipment may be excessive. It is therefore essential that the process for bringing equipment for the conceptual stage to actual routine use minimizes the risk of producing equipment that is unsuitable for the job. Fortunately, approaches for accomplishing this have already been developed in both the industrial and commercial sectors. One such approach, the Low Risk Transition Plan (LRTP) is described to show it can be applied to the production of reliable safeguards equipment

  18. Drinking patterns and adherence to "low-risk" guidelines among community-residing older adults.

    Science.gov (United States)

    Lewis, Ben; Garcia, Christian C; Nixon, Sara Jo

    2018-06-01

    Older adults constitute a rapidly expanding proportion of the U.S. Contemporary studies note the increasing prevalence of alcohol consumption in this group. Thus, understanding alcohol effects, consumption patterns, and associated risks in aging populations constitute critical areas of study with increasing public health relevance. Participants (n = 643; 292 women; ages 21-70) were community residing adult volunteers. Primary measures of interest included four patterns of alcohol consumption (average [oz./day]; typical quantity [oz./occasion]; frequency [% drinking days]; and maximal quantity [oz.]). Regression analyses explored associations between these measures, age, and relevant covariates. Subsequent between-group analyses investigated differences between two groups of older adults and a comparator group of younger adults, their adherance to "low-risk" guidelines, and whether alcohol-associated risks differed by age and adherence pattern. Average consumption did not vary by age or differ between age groups. In contrast, markedly higher frequencies and lower quantities of consumption were observed with increasing age. These differences persisted across adherence categories and were evident even in the oldest age group. Exceeding "low-risk" guidelines was associated with greater risk for alcohol-related problems among the older groups. These results emphasize the utility of considering underlying constituent patterns of consumption in older drinkers. Findings highlight difficulties in identifying problem drinking among older adults and contribute to the few characterizations of "risky" drinking patterns in this group. Taken together, our data contribute to literatures of import for the design and enhancement of screening, prevention, and education initiatives directed toward aging adults. Copyright © 2018. Published by Elsevier B.V.

  19. Determinants of prenatal health care utilisation by low-risk women: a prospective cohort study.

    Science.gov (United States)

    Feijen-de Jong, Esther I; Jansen, Danielle E M C; Baarveld, Frank; Boerleider, Agatha W; Spelten, Evelien; Schellevis, François; Reijneveld, Sijmen A

    2015-06-01

    Prenatal health care is pivotal in providing adequate prevention and care to pregnant women. We examined the determinants of inadequate prenatal health care utilisation by low-risk women in primary midwifery-led care in the Netherlands. We used longitudinal data from the population-based DELIVER study with 20 midwifery practices across the Netherlands in 2009 and 2010 as the experimental setting. The participants were 3070 pregnant women starting pregnancy care in primary midwifery care. We collected patient-reported data on potential determinants of prenatal care utilisation derived from the Andersen model. Prenatal health care utilisation was measured by a revised version of the Kotelchuck Index, which measures a combination of care entry and number of visits. Low-risk pregnant women (not referred during pregnancy) were more likely to use prenatal care inadequately if they intended to deliver at a hospital, if they did not use folic acid adequately periconceptionally, or if they were exposed to cigarette smoke during pregnancy. Among those who were referred to secondary care, women reporting a chronic illnesses or disabilities, and women who did not use folic acid periconceptionally were more likely to make inadequate use of prenatal care. Inadequate prenatal health care use in primary midwifery care is more likely in specific groups, and the risk groups differ when women are referred to secondary care. The findings suggest routes that can target interventions to women who are at risk of not adequately using prenatal prevention and care services. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  20. Factors associated with the prevalence of periodontal disease in low-risk pregnant women

    Science.gov (United States)

    2012-01-01

    Objective To evaluate the prevalence of periodontal disease (PD) among Brazilian low-risk pregnant women and its association with sociodemographic factors, habits and oral hygiene. Method This cross-sectional study included 334 low-risk pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. Independent variables were: age, race/color, schooling, marital status, parity, gestational age, smoking habit, alcohol and drugs consumption, use of medication, presence of any systemic diseases and BMI (body mass index). Statistical analyses provided prevalence ratios and their respective 95%CI and also a multivariate analysis. Results The prevalence of PD was 47% and significantly associated with higher gestational age (PR 1.40; 1.01 - 1.94 for 17-24 weeks and PR 1.52; 1.10 - 2.08 for 25-32 weeks), maternal age 25-29 years, obesity (PR 1.65; 1.02 - 2.68) and the presence of gingival bleeding on probing (ORadj 2.01, 95%CI 1.41 - 2.88). Poor oral hygiene was associated with PD by the mean values of plaque and bleeding on probing indexes significantly greater in PD group. Conclusions The prevalence of PD is high and associated with gingival bleeding on probing, more advanced gestational age and obesity. A program of oral health care should be included in prenatal care for early pregnancy, especially for low-income populations. PMID:22273008

  1. Outcome of pregnancy subsequent to chemotherapy with actinomycin-D in low risk gestational trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2017-07-01

    Methods: A retrospective cohort study was conducted on patients with GTN who were referred to Firoozgar and Mirza Koochak Khan teaching hospitals during 10 years, starting from 2004. The inclusion criterion was patients with low-risk persistent GTN after molar pregnancy, EP, and abortion, that treated with single agent chemotherapy actinomycin-D. After following the patients for 12 months, patients with serum βHCG lower than 5 mIU/ml, who intended to have child were allowed to become pregnant. The following items were observed in the study: age, body mass index (BMI, parity, chemotherapy duration, and pregnancy outcomes such as spontaneous abortion or preterm labor, pre-eclampsia, stillbirth, fetal malformation, and repeated molar pregnancy. Results: 74 patients were monitored, 83.78% of them had uncomplicated pregnancy and labor, 4.05% had the abortion, 4.05% had second molar pregnancy, 2.7% had pre-eclampsia, 5.40% had preterm labor. Moreover, stillbirth and malformation did not occur in this study even after chemotherapy treatment. There was not any significant correlation between age, BMI, parity, and chemotherapy duration with pregnancy outcomes. Conclusion: The outcomes of pregnancy after chemotherapy with actinomycin-D is similar to the general population who did not have chemotherapy. The abortion rate and repeated molar pregnancy were similar between population and sample too. Thus, the study shows that the cured patients with low-risk GTN have as much chance of having a normal pregnancy as normal women. In other words, treatment with actinomycin-D does not have any adverse effect in future pregnancies.

  2. Prospective Validation of Modified NEXUS Cervical Spine Injury Criteria in Low-risk Elderly Fall Patients

    Directory of Open Access Journals (Sweden)

    John Tran

    2016-05-01

    Full Text Available Introduction: The National Emergency X-radiography Utilization Study (NEXUS criteria are used extensively in emergency departments to rule out C-spine injuries (CSI in the general population. Although the NEXUS validation set included 2,943 elderly patients, multiple case reports and the Canadian C-Spine Rules question the validity of applying NEXUS to geriatric populations. The objective of this study was to validate a modified NEXUS criteria in a low-risk elderly fall population with two changes: a modified definition for distracting injury and the definition of normal mentation. Methods: This is a prospective, observational cohort study of geriatric fall patients who presented to a Level I trauma center and were not triaged to the trauma bay. Providers enrolled non-intoxicated patients at baseline mental status with no lateralizing neurologic deficits. They recorded midline neck tenderness, signs of trauma, and presence of other distracting injury. Results: We enrolled 800 patients. One patient fall event was excluded due to duplicate enrollment, and four were lost to follow up, leaving 795 for analysis. Average age was 83.6 (range 65-101. The numbers in parenthesis after the negative predictive value represent confidence interval. There were 11 (1.4% cervical spine injuries. One hundred seventeen patients had midline tenderness and seven of these had CSI; 366 patients had signs of trauma to the face/neck, and 10 of these patients had CSI. Using signs of trauma to the head/neck as the only distracting injury and baseline mental status as normal alertness, the modified NEXUS criteria was 100% sensitive (CI [67.9-100] with a negative predictive value of 100 (98.7-100. Conclusion: Our study suggests that a modified NEXUS criteria can be safely applied to low-risk elderly falls.

  3. Prospective Validation of Modified NEXUS Cervical Spine Injury Criteria in Low-risk Elderly Fall Patients.

    Science.gov (United States)

    Tran, John; Jeanmonod, Donald; Agresti, Darin; Hamden, Khalief; Jeanmonod, Rebecca K

    2016-05-01

    The National Emergency X-radiography Utilization Study (NEXUS) criteria are used extensively in emergency departments to rule out C-spine injuries (CSI) in the general population. Although the NEXUS validation set included 2,943 elderly patients, multiple case reports and the Canadian C-Spine Rules question the validity of applying NEXUS to geriatric populations. The objective of this study was to validate a modified NEXUS criteria in a low-risk elderly fall population with two changes: a modified definition for distracting injury and the definition of normal mentation. This is a prospective, observational cohort study of geriatric fall patients who presented to a Level I trauma center and were not triaged to the trauma bay. Providers enrolled non-intoxicated patients at baseline mental status with no lateralizing neurologic deficits. They recorded midline neck tenderness, signs of trauma, and presence of other distracting injury. We enrolled 800 patients. One patient fall event was excluded due to duplicate enrollment, and four were lost to follow up, leaving 795 for analysis. Average age was 83.6 (range 65-101). The numbers in parenthesis after the negative predictive value represent confidence interval. There were 11 (1.4%) cervical spine injuries. One hundred seventeen patients had midline tenderness and seven of these had CSI; 366 patients had signs of trauma to the face/neck, and 10 of these patients had CSI. Using signs of trauma to the head/neck as the only distracting injury and baseline mental status as normal alertness, the modified NEXUS criteria was 100% sensitive (CI [67.9-100]) with a negative predictive value of 100 (98.7-100). Our study suggests that a modified NEXUS criteria can be safely applied to low-risk elderly falls.

  4. Distinct evolutionary mechanisms for genomic imbalances in high-risk and low-risk neuroblastomas

    Directory of Open Access Journals (Sweden)

    Gisselsson David

    2007-09-01

    Full Text Available Abstract Background Neuroblastoma (NB is the most common extracranial solid tumour of childhood. Several genomic imbalances correlate to prognosis in NB, with structural rearrangements, including gene amplification, in a near-diploid setting typically signifying high-risk tumours and numerical changes in a near-triploid setting signifying low-risk tumours. Little is known about the temporal sequence in which these imbalances occur during the carcinogenic process. Methods We have reconstructed the appearance of cytogenetic imbalances in 270 NBs by first grouping tumours and imbalances through principal component analysis and then using the number of imbalances in each tumour as an indicator of evolutionary progression. Results Tumours clustered in four sub-groups, dominated respectively by (1 gene amplification in double minute chromosomes and few other aberrations, (2 gene amplification and loss of 1p sequences, (3 loss of 1p and other structural aberrations including gain of 17q, and (4 whole-chromosome gains and losses. Temporal analysis showed that the structural changes in groups 1–3 were acquired in a step-wise fashion, with loss of 1p sequences and the emergence of double minute chromosomes as the earliest cytogenetic events. In contrast, the gains and losses of whole chromosomes in group 4 occurred through multiple simultaneous events leading to a near-triploid chromosome number. Conclusion The finding of different temporal patterns for the acquisition of genomic imbalances in high-risk and low-risk NBs lends strong support to the hypothesis that these tumours are biologically diverse entities, evolving through distinct genetic mechanisms.

  5. Factors associated with the prevalence of periodontal disease in low-risk pregnant women

    Directory of Open Access Journals (Sweden)

    Vogt Marianna

    2012-01-01

    Full Text Available Abstract Objective To evaluate the prevalence of periodontal disease (PD among Brazilian low-risk pregnant women and its association with sociodemographic factors, habits and oral hygiene. Method This cross-sectional study included 334 low-risk pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. Independent variables were: age, race/color, schooling, marital status, parity, gestational age, smoking habit, alcohol and drugs consumption, use of medication, presence of any systemic diseases and BMI (body mass index. Statistical analyses provided prevalence ratios and their respective 95%CI and also a multivariate analysis. Results The prevalence of PD was 47% and significantly associated with higher gestational age (PR 1.40; 1.01 - 1.94 for 17-24 weeks and PR 1.52; 1.10 - 2.08 for 25-32 weeks, maternal age 25-29 years, obesity (PR 1.65; 1.02 - 2.68 and the presence of gingival bleeding on probing (ORadj 2.01, 95%CI 1.41 - 2.88. Poor oral hygiene was associated with PD by the mean values of plaque and bleeding on probing indexes significantly greater in PD group. Conclusions The prevalence of PD is high and associated with gingival bleeding on probing, more advanced gestational age and obesity. A program of oral health care should be included in prenatal care for early pregnancy, especially for low-income populations.

  6. Variants of Moreau's sweeping process

    International Nuclear Information System (INIS)

    Siddiqi, A.H.; Manchanda, P.

    2001-07-01

    In this paper we prove the existence and uniqueness of two variants of Moreau's sweeping process -u'(t) is an element of Nc (t) (u(t)), where in one variant we replace u(t) by u'(t) in the right-hand side of the inclusion and in the second variant u'(t) and u(t) are respectively replaced by u''(t) and u'(t). (author)

  7. Hairy cell leukemia-variant

    International Nuclear Information System (INIS)

    Quadri, Mohammad I.; Al-Sheikh, Iman H.

    2001-01-01

    Hairy cell leukaemia variant is a very rare chronic lymphoproliferative disorder and is closely related to hairy cell leukemia. We hereby describe a case of hairy cell leukaemia variant for the first time in Saudi Arabia. An elderly Saudi man presented with pallor, massive splenomegaly, and moderate hepatomegaly. Hemoglobin was 7.7 g/dl, Platelets were 134 x109/l and white blood count was 140x10 9/l with 97% being abnormal lymphoid cells with cytoplasmic projections. The morphology, cytochemistry, and immunophenotype of the lymphoid cells were classical of hairy cell leukaemia variant. The bone marrow was easily aspirated and findings were consistent with hairy cell leukaemia variant. (author)

  8. Patient perceptions of risky drinking: Knowledge of daily and weekly low-risk guidelines and standard drink sizes.

    Science.gov (United States)

    Sprague, Debra J; Vinson, Daniel C

    2017-01-01

    Effective intervention for risky drinking requires that clinicians and patients know low-risk daily and weekly guidelines and what constitutes a "standard drink." The authors hypothesized that most patients lack this knowledge, and that education is required. Following primary care visits, patients completed anonymous exit questionnaires that included the 3 Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questions, "How many drinks (containing alcohol) can you safely have in one day?" and questions about size, in ounces, of a standard drink of wine, beer, and liquor. Descriptive analyses were done in Stata. Of 1,331 respondents (60% female, mean age: 49.6, SD = 17.5), 21% screened positive on the AUDIT-C for risky drinking. Only 10% of those accurately estimated daily low-risk limits, with 9% accurate on weekly limits, and half estimated low-risk limits at or below guidelines. Fewer than half who checked "Yes" to "Do you know what a 'standard drink' is?" provided accurate answers for beer, wine, or liquor. Patients with a positive screen were twice as likely to say they knew what a standard drink is, but only a third gave accurate estimates. When asked about plans in the next month regarding change in drinking behavior, 23% with a positive AUDIT-C indicated they were at least considering a change. Most patients in primary care don't know specifics of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines for low-risk drinking. Exploring patient perceptions of low-risk guidelines and current drinking behavior may reveal discrepancies worth discussing. For risky drinkers, most of whom don't know daily and weekly low-risk guidelines or standard drink sizes, education can be vital in intervening. Findings suggest the need for detailed and explicit social marketing and communication on exactly what low-risk drinking entails.

  9. Product Variant Master as a Means to Handle Variant Design

    DEFF Research Database (Denmark)

    Hildre, Hans Petter; Mortensen, Niels Henrik; Andreasen, Mogens Myrup

    1996-01-01

    be implemented in the CAD system I-DEAS. A precondition for high degree of computer support is identification of a product variant master from which new variants can be derived. This class platform defines how a product build up fit certain production methods and rules governing determination of modules...

  10. Pre-Feedback Risk Expectancies and Reception of Low-Risk Health Feedback: Absolute and Comparative Lack of Reassurance.

    Science.gov (United States)

    Gamp, Martina; Renner, Britta

    2016-11-01

    Personalised health-risk assessment is one of the most common components of health promotion programs. Previous research on responses to health risk feedback has commonly focused on the reception of bad news (high-risk feedback). The reception of low-risk feedback has been comparably neglected since it is assumed that good news is reassuring and readily received. However, field studies suggest mixed responses to low-risk health feedback. Accordingly, we examine whether pre-feedback risk expectancies can mitigate the reassuring effects of good news. In two studies (N = 187, N = 565), after assessing pre-feedback risk expectancies, participants received low-risk personalised feedback about their own risk of developing (the fictitious) Tucson Chronic Fatigue Syndrome (TCFS). Study 2 also included peer TCFS risk status feedback. Afterwards, self- and peer-related risk perception for TCFS was assessed. In both studies, participants who expected to be at high risk but received good news (unexpected low-risk feedback) showed absolute lack of reassurance. Specifically, they felt at significantly greater TCFS risk than participants who received expected good news. Moreover, the unexpected low-risk group even believed that their risk was as high as (Study 1) or higher (Study 2) than that of their peers (comparative lack of reassurance). Results support the notion that high pre-feedback risk expectancies can mitigate absolute and comparative reassuring effects of good news. © 2016 The International Association of Applied Psychology.

  11. Absence of survival benefit of radioactive iodine (RAI) after thyroidectomy in low risk differentiated thyroid cancer (DTC) patients

    International Nuclear Information System (INIS)

    Schwartz, C.; Fieffe, S.; Pochart, J.M.; Bonnetain, F.; Gauthier, M.; Cueff, A.; Crevisy, E.; Dygai-Cochet, I.; Toubeau, M.

    2012-01-01

    After thyroidectomy, the goal of the first dose of radioactive iodine (RAI) is remnant ablation to facilitate the initial staging with the post-therapy scan and to facilitate the early detection of recurrences. The purpose of this study is to the survival benefit of RAI in low-risk thyroid cancer patients. Using Cancer thyroid registry of Marne Ardennes (1041 patients) and hospital data base of centre Leclerc (257 patients), we included all differentiated thyroid cancer (DTC) patients at low risk from 1975 to 2005. Median follow-up was 10.3 years, during which 19 recurrences, 61 other malignant diseases and 105 deaths were registered. 387 patients (30%) received no RAI and 911 had RAI (70%). If we confirmed that some clinical characteristics were associated with RAI intake, the study failed to demonstrate any survival benefit of RAI in low risk DTC patients

  12. Absence of survival benefit of radioactive iodine (RAI) after thyroidectomy in low risk differentiated thyroid cancer (DTC) patients

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, C.; Fieffe, S.; Pochart, J.M. [Endocrinology Nuclear Medicine, Institut Jean Godinot, Reims (France); Bonnetain, F.; Gauthier, M.; Cueff, A. [Statistics and Epidemiology, Centre Georges Francois Leclerc, Dijon (France); Crevisy, E.; Dygai-Cochet, I.; Toubeau, M. [Nuclear Medicine, Centre Georges Francois Leclerc, Dijon (France)

    2012-07-01

    After thyroidectomy, the goal of the first dose of radioactive iodine (RAI) is remnant ablation to facilitate the initial staging with the post-therapy scan and to facilitate the early detection of recurrences. The purpose of this study is to the survival benefit of RAI in low-risk thyroid cancer patients. Using Cancer thyroid registry of Marne Ardennes (1041 patients) and hospital data base of centre Leclerc (257 patients), we included all differentiated thyroid cancer (DTC) patients at low risk from 1975 to 2005. Median follow-up was 10.3 years, during which 19 recurrences, 61 other malignant diseases and 105 deaths were registered. 387 patients (30%) received no RAI and 911 had RAI (70%). If we confirmed that some clinical characteristics were associated with RAI intake, the study failed to demonstrate any survival benefit of RAI in low risk DTC patients

  13. HTLV-I/II and blood donors: determinants associated with seropositivity in a low risk population

    Directory of Open Access Journals (Sweden)

    Bernadette Catalan Soares

    2003-08-01

    Full Text Available OBJECTIVE: Blood donors in Brazil have been routinely screened for HTLV-I/II since 1993. A study was performed to estimate the prevalence of HTLV-I/II infection in a low risk population and to better understand determinants associated with seropositivity. METHODS: HTLV-I/II seropositive (n=135, indeterminate (n=167 and seronegative blood donors (n=116 were enrolled in an open prevalence prospective cohort study. A cross-sectional epidemiological study of positive, indeterminate and seronegative HTLV-I/II subjects was conducted to assess behavioral and environmental risk factors for seropositivity. HTLV-I/II serological status was confirmed using enzyme-linked immunosorbent assay (EIA and Western blot (WB. RESULTS: The three groups were not homogeneous. HTLV-I/II seropositivity was associated to past blood transfusion and years of schooling, a marker of socioeconomic status, and use of non-intravenous illegal drugs. CONCLUSIONS: The study results reinforce the importance of continuous monitoring and improvement of blood donor selection process.

  14. Peripheral QCT: a low risk procedure to identify women predisposed to osteoporosis

    International Nuclear Information System (INIS)

    Mueller, A.; Rueegsegger, E.; Rueegsegger, P.

    1989-01-01

    A low-risk procedure is described for the precise quantitation of changes of trabecular and cortical bone density at peripheral measuring sites. The method is based on quantitative computed tomography (QCT). Bone parameters are calculated for a sample volume common to all examinations of a patient. This is achieved by matching stacks of tomograms according to the cross sectional area of the bone measured. With the help of a special-purpose CT system the described procedure enables a reproducibility for trabecular and cortical bone parameters of 0.3% (1 SD) at a local radiation dose of of 0.1 mSv (10 mrem). The method was used to assess the individual changes in bone density of 39 perimenopausal women during an observation period of 2 to 3 years. The results are grouped according to their menstrual state. Regularly menstruating women experience minute or no changes in bone density. After menopause the interindividual differences are considerable: some women lose bone excessively, others remain relatively stable. The frequency distribution of the rate of bone loss appears to be bimodal. Hence women can be classified in fast losers and slow losers. We conclude that the rate of bone loss may be most helpful in the identification of those women predisposed to osteoporosis. (author)

  15. Early psychomotor development of low-risk preterm infants: Influence of gestational age and gender.

    Science.gov (United States)

    Romeo, Domenico M; Brogna, Claudia; Sini, Francesca; Romeo, Mario G; Cota, Francesco; Ricci, Daniela

    2016-07-01

    The influence of gestational age and gender in the neurodevelopment of infants during the first year of age is not yet fully elucidated. The purpose of this study was to identify the early occurrence of neurodevelopmental differences, between very preterm, late preterm and term born infants and the possible influence of the gender on the neurodevelopment in early infancy. A total of 188 low-risk infants, 69 very preterms, 71 late-preterms, and 48 term infants were assessed at 3, 6, 9, 12 months corrected age using the Hammersmith Infant Neurological Examination (HINE). At two years of age infants performed the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development. The main results indicate that both very preterms and late-preterms showed significant lower global scores than term born infants at each evaluation (p development of infants assessed during the first 2 years of life. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  16. Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

    Directory of Open Access Journals (Sweden)

    Cecatti Jose G

    2010-11-01

    Full Text Available Abstract Objective To evaluate the association of periodontal disease (PD in pregnancy with some adverse perinatal outcomes. Method This cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB, low birth weight (LBW, small for gestational age (SGA neonates and prelabor rupture of membranes (PROM were evaluated using Risk Ratios (95%CI and Population Attributable Risk Fractions. Results PD was associated with a higher risk of PTB (RRadj. 3.47 95%CI 1.62-7.43, LBW (RRadj. 2.93 95%CI 1.36-6.34 and PROM (RRadj. 2.48 95%CI 1.35-4.56, but not with SGA neonates (RR 2.38 95%CI 0.93 - 6.10. Conclusions PD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women.

  17. Maternal and newborn morbidity by birth facility among selected United States 2006 low-risk births.

    Science.gov (United States)

    Wax, Joseph R; Pinette, Michael G; Cartin, Angelina; Blackstone, Jacquelyn

    2010-02-01

    We sought to evaluate perinatal morbidity by delivery location (hospital, freestanding birth center, and home). Selected 2006 US birth certificate data were accessed online from the Centers for Disease Control and Prevention. Low-risk maternal and newborn outcomes were tabulated and compared by birth facility. A total of 745,690 deliveries were included, of which 733,143 (97.0%) occurred in hospital, 4661 (0.6%) at birth centers, and 7427 (0.9%) at home. Compared with hospital deliveries, home and birthing center deliveries were associated with more frequent prolonged and precipitous labors. Home births experienced more frequent 5-minute Apgar scores home and birthing center deliveries were associated with less frequent chorioamnionitis, fetal intolerance of labor, meconium staining, assisted ventilation, neonatal intensive care unit admission, and birthweight Home births are associated with a number of less frequent adverse perinatal outcomes at the expense of more frequent abnormal labors and low 5-minute Apgar scores. Copyright 2010 Mosby, Inc. All rights reserved.

  18. Placental histological inflammation and reproductive tract infections in a low risk pregnant population in Latvia.

    Science.gov (United States)

    Rezeberga, Dace; Lazdane, Gunta; Kroica, Juta; Sokolova, Ludmila; Donders, Gilbert G G

    2008-01-01

    To investigate the correlation of reproductive tract infections (RTI) and endogenous vaginal flora at first antenatal consultation with placental histological inflammation. In a follow-up study, 154 low risk women with no miscarriage risk factors were examined for the presence of Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella vaginalis, Streptococcus agalactiae (GBS), Staphylococcus aureus, Enterococcus faecalis (GDS) and bacterial vaginosis (BV). At delivery, outcome data were collected and the histology of the placenta was studied. Some 85 (56.3%) of all pregnant women had RTI or endogenous vaginal flora. Placental histological inflammation correlated with genital tract colonisation with G. vaginalis (p =0.013), BV (p =0.031), S. aureus (p =0.04) and aerobic vaginitis (p =0.017). BV and BV-related G. vaginalis correlated with the presence of parietal and placental chorioamnionitis in 53.8 and 43.5% of cases. Genital tract colonisation with GDS and other aerobic flora in combination with inflammatory vaginitis correlated with the presence of funisitis in 33.3 and 40.0% of cases. Mycoplasmas increased the risk for intrauterine infection only when present in combination with other RTIs (p =0.023). Histological placental inflammation is associated with both BV and genital tract colonisation with aerobic bacteria, while funisitis is associated with colonisation of aerobic bacteria at first prenatal visit before the 17th gestational week.

  19. Obesity and pregnancy: a transversal study from a low-risk maternity.

    Science.gov (United States)

    Calderon, Ana Carolina S; Quintana, Silvana M; Marcolin, Alessandra C; Berezowski, Aderson T; Brito, Luiz Gustavo O; Duarte, Geraldo; Cavalli, Ricardo C

    2014-07-28

    Obesity is a public health problem and is increasing in all populations, including pregnant women. It influences maternal and neonatal outcomes; however, data are scarce in developing countries. We aimed to compare perinatal results between obese and non-obese pregnant women in a low-risk maternity. Transversal study of 1,779 40-week-pregnancies from 2005 to 2009 that completed a standard questionnaire with sociodemographic, obstetrical and neonatal variables and performed an ultrasound with amniotic fluid index (AFI) measurement and foetal vitality (FBP, non-stress test). They were analysed about their association with obesity on pregnancy. When compared with non-obese women, the group of obese patients had higher systolic (118.1 vs 109.2 mmHg; p < 0.01) and diastolic (76.6 vs 70.4 mmHg; p < 0.01) pressure levels, AFI (12.52 vs. 9.61 cm; p = 0.02), presence of meconium on labour (20.52 vs. 14.67%; p = 0.02), birthweight (3602 vs. 3437 g; p < 0.01) and caesarean section (39.74 vs. 29.98%, p < 0.01). Labour induction before 40 weeks in the antenatal period associated with foetal weight estimation should be considered as a recommendation for decreasing high percentages of caesarean delivery found in obese women.

  20. Identifying Emergency Department Patients at Low Risk for a Variceal Source of Upper Gastrointestinal Hemorrhage.

    Science.gov (United States)

    Klein, Lauren R; Money, Joel; Maharaj, Kaveesh; Robinson, Aaron; Lai, Tarissa; Driver, Brian E

    2017-11-01

    Assessing the likelihood of a variceal versus nonvariceal source of upper gastrointestinal bleeding (UGIB) guides therapy, but can be difficult to determine on clinical grounds. The objective of this study was to determine if there are easily ascertainable clinical and laboratory findings that can identify a patient as low risk for a variceal source of hemorrhage. This was a retrospective cohort study of adult ED patients with UGIB between January 2008 and December 2014 who had upper endoscopy performed during hospitalization. Clinical and laboratory data were abstracted from the medical record. The source of the UGIB was defined as variceal or nonvariceal based on endoscopic reports. Binary recursive partitioning was utilized to create a clinical decision rule. The rule was internally validated and test characteristics were calculated with 1,000 bootstrap replications. A total of 719 patients were identified; mean age was 55 years and 61% were male. There were 71 (10%) patients with a variceal UGIB identified on endoscopy. Binary recursive partitioning yielded a two-step decision rule (platelet count > 200 × 10 9 /L and an international normalized ratio [INR] study must be externally validated before widespread use, patients presenting to the ED with an acute UGIB with platelet count of >200 × 10 9 /L and an INR of upper gastrointestinal hemorrhage. © 2017 by the Society for Academic Emergency Medicine.

  1. Comparing variation in hospital rates of cesarean delivery among low-risk women using 3 different measures.

    Science.gov (United States)

    Armstrong, Joanne C; Kozhimannil, Katy B; McDermott, Patricia; Saade, George R; Srinivas, Sindhu K

    2016-02-01

    This report describes the development of a measure of low-risk cesarean delivery by the Society for Maternal-Fetal Medicine (SMFM). Safely lowering the cesarean delivery rate is a priority for maternity care clinicians and health care delivery systems. Therefore, hospital quality assurance programs are increasingly tracking cesarean delivery rates among low-risk pregnancies. Two commonly used definitions of "low risk" are available, the Joint Commission (JC) and the Agency for Healthcare Research and Quality (AHRQ) measures, but these measures are not clinically comprehensive. We sought to refine the definition of the low-risk cesarean delivery rate to enhance the validity of the metric for quality measurement. We created this refined definition-called the SMFM definition-and compared it to the JC and AHRQ measures using claims-based data from the 2011 Nationwide Inpatient Sample of >863,000 births in 612 hospitals. Using these definitions, we calculated means and interquartile ranges (25th-75th percentile range) for hospital low-risk cesarean delivery rates, stratified by hospital size, teaching status, urban/rural location, and payer mix. Across all hospitals, the mean low-risk cesarean delivery rate was lowest for the SMFM definition (12.65%), but not substantially different from the JC and AHRQ measures (13.12% and 13.29%, respectively). We empirically examined the SMFM definition to ensure its validity and utility. This refined definition performs similarly to existing measures and has the added advantage of clinical perspective, enhanced face validity, and ease of use. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Risk indicators for dystocia in low-risk nulliparous women: a study on lifestyle and anthropometrical factors

    DEFF Research Database (Denmark)

    Kjaergaard, H; Dykes, A K; Ottesen, B

    2010-01-01

    We examined background information and course of labour from a cohort of 2,810 low-risk nulliparas to identify possible lifestyle and anthropometrical risk indicators for dystocia. Criteria for dystocia: cervical dilatation or =4 h per week appeared protective for dystocia (OR 0.63, CI 0.45-0.89)......We examined background information and course of labour from a cohort of 2,810 low-risk nulliparas to identify possible lifestyle and anthropometrical risk indicators for dystocia. Criteria for dystocia: cervical dilatation or =4 h per week appeared protective for dystocia (OR 0.63, CI 0...

  3. A new paradigm in low-risk papillary microcarcinoma: active surveillance

    Directory of Open Access Journals (Sweden)

    Alex González Bóssolo

    2017-09-01

    Full Text Available Classical papillary thyroid microcarcinoma (PTMC is a variant of papillary thyroid carcinoma (PTC known to have excellent prognosis. It has a mortality of 0.3%, even in the presence of distance metastasis. The latest American Thyroid Association guidelines state that although lobectomy is acceptable, active surveillance can be considered in the appropriate setting. We present the case of a 37-year-old female with a history of PTMC who underwent surgical management consisting of a total thyroidectomy. Although she has remained disease-free, her quality of life has been greatly affected by the sequelae of this procedure. This case serves as an excellent example of how first-line surgical treatment may result more harmful than the disease itself.

  4. Foot length measurements of newborns of high and low risk pregnancies.

    Science.gov (United States)

    Salge, Ana Karina Marques; Rocha, Érika Lopes; Gaíva, Maria Aparecida Munhoz; Castral, Thaíla Correa; Guimarães, Janaína Valadares; Xavier, Raphaela Maioni

    2017-03-09

    Comparing foot length measurements of newborns in high and low risk pregnancies at a public hospital in Goiânia, GO, Brazil. A cross-sectional study carried out between April, 2013 and May, 2015, with a sample consisting of 180 newborns; 106 infants of women from high-risk pregnancies and 74 of women from low-risk pregnancies. Data were descriptively analyzed. Foot length measurement was performed using a stiff transparent plastic ruler, graduated in millimeters. The length of both feet was measured from the tip of the hallux (big toe) to the end of the heel. A statistically significant relationship was found between the foot length and newborn's weight, between the cephalic and thoracic perimeters in the high-risk group and between the cephalic perimeter in the control group. There is a need for creating cut-off points to identify newborns with intrauterine growth disorders using foot length. Comparar as medidas do comprimento hálux-calcâneo de recém-nascidos em gestações de alto e baixo risco em um hospital público de Goiânia, GO. Estudo transversal, realizado no período de abril de 2013 a maio de 2015, cuja amostra constituiu-se de 180 recém-nascidos, 106 filhos de mulheres com gestação de alto risco e 74 de mulheres com gestação de baixo risco. Os dados foram analisados descritivamente. A medida do comprimento hálux-calcâneo foi realizada utilizando-se de régua plástica transparente rígida, graduada em milímetros. Foram medidos ambos os pés, aferindo-se o comprimento da ponta do hálux até a extremidade do calcâneo. Foi encontrada relação estatisticamente significante entre o comprimento hálux-calcâneo e o peso do recém-nascido, entre os perímetros cefálico e torácico no grupo de alto risco e entre o perímetro cefálico no grupo controle. Existe necessidade da criação de pontos de corte para identificar recém-nascidos com desvios de crescimento intrauterino utilizando-se do comprimento hálux-calcâneo. Comparar las mediciones

  5. Ultrasonographic study and Doppler flow velocimetry of maternal kidneys and liver in low-risk pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Daher, Cibele Helena; Gomes, Andrea Cavalanti; Kobayashi, Sergio; Chammas, Maria Cristina, E-mail: cibeledaher@hotmail.com [Universidade de Sao Paulo (In-Rad/HC-FMUSP), Sao Paulo, SP (Brazil). Hospital das Clinicas. Inst. de Radiologia; Cerri, Giovanni Guido [Universidade de Sao Paulo (FMUSP), Sao Paulo, SP (Brazil). Fac. de Medicina

    2015-05-15

    Objective: longitudinal study with B-mode ultrasonography and Doppler ultrasonography of maternal kidneys and liver in low-risk pregnancy, to establish and quantify normality parameters, correlating them with physiological changes. Materials and methods: twenty-five pregnant women were assessed and selected to participate in the study, each of them undergoing four examinations at the first, second, third trimesters and postpartum. Results: findings during pregnancy were the following: increased renal volume, pyelocaliceal dilatation with incidence of 45.4% in the right kidney, and 9% in the left kidney; nephrolithiasis, 18.1% in the right kidney, 13.6% in the left kidney. With pyelocaliceal dilatation, mean values for resistivity index were: 0.68 for renal arteries; 0.66 for segmental arteries; 0.64 for interlobar arteries; 0.64 for arcuate arteries. Without pyelocaliceal dilatation, 0.67 for renal arteries; 0.64 for segmental arteries; 0.63 for interlobar arteries; and 0.61 for arcuate arteries. Portal vein flow velocities presented higher values in pregnancy, with mean value for maximum velocity of 28.9 cm/s, and 22.6 cm/s postpartum. The waveform pattern of the right hepatic vein presented changes persisting in the postpartum period in 31.8% of the patients. Cholelithiasis was observed in 18.1% of the patients. Conclusion: alterations in renal volume, pyelocaliceal dilatation, nephrolithiasis, cholelithiasis, changes in portal vein flow velocity, alterations in waveform pattern of the right hepatic vein, proved to be significant. (author)

  6. Applicator-guided volumetric-modulated arc therapy for low-risk endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cilla, Savino, E-mail: savinocilla@gmail.com [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Macchia, Gabriella [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Sabatino, Domenico [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Digesù, Cinzia; Deodato, Francesco [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Piermattei, Angelo [Physics Institute, Università Cattolica del Sacro Cuore, Rome (Italy); De Spirito, Marco [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Morganti, Alessio G. [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Radiation Oncology Unit, Università Cattolica del Sacro Cuore, Rome (Italy)

    2013-04-01

    The aim of this study was to report the feasibility of volumetric-modulated arc therapy (VMAT) in the postoperative irradiation of the vaginal vault. Moreover, the VMAT technique was compared with 3D conformal radiotherapy (3D-CRT) and fixed-field intensity-modulated radiotherapy (IMRT), in terms of target coverage and organs at risk sparing. The number of monitor units and the delivery time were analyzed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a 2D array of ionization chambers. Twelve patients with endometrial carcinoma who underwent radical hystero-adenexectomy and fixed-field IMRT treatments were retrospectively included in this analysis; for each patient, plans were compared in terms of dose-volume histograms, homogeneity index, and conformity indexes. All techniques met the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformity at all dose levels. VMAT resulted in significant reduction of rectal and bladder volumes irradiated at all dose levels compared with 3D-CRT. No significant differences were found with respect to IMRT. Moreover, a significant improvement of the dose conformity was reached by VMAT technique not only at the 95% dose level (0.74 vs. 0.67 and 0.62) but also at 50% and 75% levels of dose prescription. In addition, VMAT plans showed a significant reduction of monitor units by nearly 28% with respect to IMRT, and reduced treatment time from 11 to <3 minutes for a single 6-Gy fraction. In conclusion, VMAT plans can be planned and carried out with high quality and efficiency for the irradiation of vaginal vault alone, providing similar or better sparing of organs at risk to fixed-field IMRT and resulting in the most efficient treatment option. VMAT is currently our standard approach for radiotherapy of low-risk endometrial cancer.

  7. Thyroid nodules with minimal cystic changes have a low risk of malignancy

    International Nuclear Information System (INIS)

    Na, Dong Gyu; Kim, Dae Sik; Kim, Soo Jin; Kim, Ji Hoon

    2016-01-01

    The goal of this study was to determine the risk of malignancy of thyroid nodules with minimal cystic changes. A total of consecutive 1,000 thyroid nodules (≥1 cm) with final diagnoses from two institutions were included in this study. The risk of malignancy of thyroid nodules was analyzed according to the internal content, which was categorized as purely solid, minimally cystic (cystic changes ≤10%), and partially cystic (cystic changes >10%). We also assessed the risk of malignancy of nodules with minimal cystic changes depending on echogenicity and presence of any suspicious ultrasonografic (US) features. The overall frequency of purely solid, minimally cystic, and partially cystic nodules was 730/1,000 (73%), 61/1,000 (6.1%), and 209/1,000 (20.9%), respectively, with risks of malignancy of 14.8% (108/730), 3.3% (2/61), and 3.3% (7/209), respectively. The risk of malignancy of nodules with minimal cystic changes was significantly lower than that of purely solid nodules (P=0.013). The risk of malignancy of nodules with minimal cystic changes was also lower than that of purely solid nodules in the group of hypoechoic nodules (P=0.063) and in the group of nodules with suspicious US features (P=0.028), but was not significantly different from that of partially cystic nodules regardless of echogenicity or the presence of suspicious US features (P≥0.652). Thyroid nodules with minimal cystic changes have a low risk of malignancy, similar to that of partially cystic nodules regardless of echogenicity or the presence of suspicious US features. The US lexicon could define solid nodules as nodules with purely solid internal content in order to enhance the accuracy of estimated risks of malignancy

  8. Utilization of prostate brachytherapy for low risk prostate cancer: Is the decline overstated?

    Science.gov (United States)

    Safdieh, Joseph; Wong, Andrew; Weiner, Joseph P; Schwartz, David; Schreiber, David

    2016-08-01

    Several prior studies have suggested that brachytherapy utilization has markedly decreased, coinciding with the recent increased utilization of intensity modulated radiation therapy, as well as an increase in urologist-owned centers. We sought to investigate the brachytherapy utilization in a large, hospital-based registry. Men with prostate cancer diagnosed between 2004-2012 and treated with either external beam radiation and/or prostate brachytherapy were abstracted from the National Cancer Database. In order to be included, men had to be clinically staged as T1c-T2aNx-0Mx-0, Gleason 6, PSA ≤ 10.0 ng/ml. Descriptive statistics were used to analyze brachytherapy utilization over time and were compared via χ(2). Multivariate logistic regression was used to assess for covariables associated with increased brachytherapy usage. There were 89,413 men included in this study, of which 37,054 (41.6%) received only external beam radiation, and 52,089 (58.4%) received prostate brachytherapy. The use of brachytherapy declined over time from 62.9% in 2004 to 51.3% in 2012 (p facilities (60.8% in 2004 to 47.0% in 2012, p facilities (63.7% in 2004 to 53.0% in 2012, p facilities than those who lived further. The use of intensity modulated radiation therapy increased during this same time period from 18.4% in 2004 to 38.2% in 2012 (p usage. In this hospital-based registry, prostate brachytherapy usage has declined for low risk prostate cancer as intensity modulated radiation therapy usage has increased. However, it still remains the treatment of choice for 51.3% of patients as of 2012.

  9. Association of Trichomonas vaginalis and cytological abnormalities of the cervix in low risk women.

    Directory of Open Access Journals (Sweden)

    Gilbert G G Donders

    Full Text Available OBJECTIVE: Is Trichomonas vaginalis (TV an inducing factor for the development of (pre-cancerous lesions of the cervix? DESIGN: Cross sectional study. SETTING: Screening healthy Belgian women with low infection risk. SAMPLE: 63,251 consecutive liquid based cervical samples. METHODS: Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities. MAIN OUTCOME MEASURES: Association of TV and HPV with cervix dysplasia. RESULTS: The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6. In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05, mainly due to an increase in ASC-US and LSIL, but not HSIL. CONCLUSIONS: We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US.

  10. Ultrasonographic study and Doppler flow velocimetry of maternal kidneys and liver in low-risk pregnancy

    International Nuclear Information System (INIS)

    Daher, Cibele Helena; Gomes, Andrea Cavalanti; Kobayashi, Sergio; Chammas, Maria Cristina; Cerri, Giovanni Guido

    2015-01-01

    Objective: longitudinal study with B-mode ultrasonography and Doppler ultrasonography of maternal kidneys and liver in low-risk pregnancy, to establish and quantify normality parameters, correlating them with physiological changes. Materials and methods: twenty-five pregnant women were assessed and selected to participate in the study, each of them undergoing four examinations at the first, second, third trimesters and postpartum. Results: findings during pregnancy were the following: increased renal volume, pyelocaliceal dilatation with incidence of 45.4% in the right kidney, and 9% in the left kidney; nephrolithiasis, 18.1% in the right kidney, 13.6% in the left kidney. With pyelocaliceal dilatation, mean values for resistivity index were: 0.68 for renal arteries; 0.66 for segmental arteries; 0.64 for interlobar arteries; 0.64 for arcuate arteries. Without pyelocaliceal dilatation, 0.67 for renal arteries; 0.64 for segmental arteries; 0.63 for interlobar arteries; and 0.61 for arcuate arteries. Portal vein flow velocities presented higher values in pregnancy, with mean value for maximum velocity of 28.9 cm/s, and 22.6 cm/s postpartum. The waveform pattern of the right hepatic vein presented changes persisting in the postpartum period in 31.8% of the patients. Cholelithiasis was observed in 18.1% of the patients. Conclusion: alterations in renal volume, pyelocaliceal dilatation, nephrolithiasis, cholelithiasis, changes in portal vein flow velocity, alterations in waveform pattern of the right hepatic vein, proved to be significant. (author)

  11. Association of Trichomonas vaginalis and cytological abnormalities of the cervix in low risk women.

    Science.gov (United States)

    Donders, Gilbert G G; Depuydt, Christophe E; Bogers, John-Paul; Vereecken, Annie J

    2013-01-01

    Is Trichomonas vaginalis (TV) an inducing factor for the development of (pre-)cancerous lesions of the cervix? Cross sectional study. Screening healthy Belgian women with low infection risk. 63,251 consecutive liquid based cervical samples. Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities. Association of TV and HPV with cervix dysplasia. The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6). In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05), mainly due to an increase in ASC-US and LSIL, but not HSIL. We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US.

  12. Acceptability of a novel vaginal microbicide during a safety trial among low-risk women.

    Science.gov (United States)

    Bentley, M E; Morrow, K M; Fullem, A; Chesney, M A; Horton, S D; Rosenberg, Z; Mayer, K H

    2000-01-01

    The increasing recognition that women who are unable or unwilling to discuss or use condoms with their sexual partners need female-controlled methods for preventing sexually transmitted diseases (STDs), including HIV, has led to considerable focus on the development of vaginal microbicides. While many such products are being tested for safety and effectiveness, clinical trials generally overlook another key factor in a product's impact on infection rates-its acceptability to users. A Phase I clinical trial of a microbicidal gel included an assessment of the product's acceptability among 27 low-risk participants. Information on acceptability was gathered from structured interviews, participants' daily diaries and unstructured exit interviews. Participants reported only minor side effects of product use, such as itching, burning and difficulty urinating; two women developed candida infections while participating in the study. None of the side effects could be conclusively linked to use of the gel. Some women noted product discharge and messiness as drawbacks of the method, but this experience varied according to how often the women applied the gel. For example, one-third of those who used it once daily said that at least some of the time, it was too "wet or drippy," compared with two-thirds of women who inserted the gel twice a day. However, participants considered these "nuisance factors" that could be outweighed by the potential protective characteristics of the product. The majority reported that they would use the product if it were available and proven efficacious, and if they perceived that they were at risk of STD infection. Additional testing of this product is urgently needed. Furthermore, as other products approach Phase I testing, acceptability assessments should be a key component of clinical trials.

  13. Benefit of early discharge among patients with low-risk pulmonary embolism.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available Clinical guidelines recommend early discharge of patients with low-risk pulmonary embolism (LRPE. This study measured the overall impact of early discharge of LRPE patients on clinical outcomes and costs in the Veterans Health Administration population. Adult patients with ≥1 inpatient diagnosis for pulmonary embolism (PE (index date between 10/2011-06/2015, continuous enrollment for ≥12 months pre- and 3 months post-index date were included. PE risk stratification was performed using the simplified Pulmonary Embolism Stratification Index. Propensity score matching (PSM was used to compare 90-day adverse PE events (APEs [recurrent venous thromboembolism, major bleed and death], hospital-acquired complications (HACs, healthcare utilization, and costs among short (≤2 days versus long length of stay (LOS. Net clinical benefit was defined as 1 minus the combined rate of APE and HAC. Among 6,746 PE patients, 95.4% were men, 22.0% were African American, and 1,918 had LRPE. Among LRPE patients, only 688 had a short LOS. After 1:1 PSM, there were no differences in APE, but short LOS had fewer HAC (1.5% vs 13.3%, 95% CI: 3.77-19.94 and bacterial pneumonias (5.9% vs 11.7%, 95% CI: 1.24-3.23, resulting in better net clinical benefit (86.9% vs 78.3%, 95% CI: 0.84-0.96. Among long LOS patients, HACs (52 exceeded APEs (14 recurrent DVT, 5 bleeds. Short LOS incurred lower inpatient ($2,164 vs $5,100, 95% CI: $646.8-$5225.0 and total costs ($9,056 vs $12,544, 95% CI: $636.6-$6337.7. LRPE patients with short LOS had better net clinical outcomes at lower costs than matched LRPE patients with long LOS.

  14. Quantification of CT images for the classification of high- and low-risk pancreatic cysts

    Science.gov (United States)

    Gazit, Lior; Chakraborty, Jayasree; Attiyeh, Marc; Langdon-Embry, Liana; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

    2017-03-01

    Pancreatic cancer is the most lethal cancer with an overall 5-year survival rate of 7%1 due to the late stage at diagnosis and the ineffectiveness of current therapeutic strategies. Given the poor prognosis, early detection at a pre-cancerous stage is the best tool for preventing this disease. Intraductal papillary mucinous neoplasms (IPMN), cystic tumors of the pancreas, represent the only radiographically identifiable precursor lesion of pancreatic cancer and are known to evolve stepwise from low-to-high-grade dysplasia before progressing into an invasive carcinoma. Observation is usually recommended for low-risk (low- and intermediate-grade dysplasia) patients, while high-risk (high-grade dysplasia and invasive carcinoma) patients undergo resection; hence, patient selection is critically important in the management of pancreatic cysts.2 Radiologists use standard criteria such as main pancreatic duct size, cyst size, or presence of a solid enhancing component in the cyst to optimally select patients for surgery.3 However, these findings are subject to a radiologist's interpretation and have been shown to be inconsistent with regards to the presence of a mural nodule or solid component.4 We propose objective classification of risk groups based on quantitative imaging features extracted from CT scans. We apply new features that represent the solid component (i.e. areas of high intensity) within the cyst and extract standard texture features. An adaptive boost classifier5 achieves the best performance with area under receiver operating characteristic curve (AUC) of 0.73 and accuracy of 77.3% for texture features. The random forest classifier achieves the best performance with AUC of 0.71 and accuracy of 70.8% with the solid component features.

  15. Low Risk of Cervical Cancer/Precancer Among Most Women Under Surveillance Postcolposcopy.

    Science.gov (United States)

    Demarco, Maria; Cheung, Li C; Kinney, Walter K; Wentzensen, Nicolas; Lorey, Thomas S; Fetterman, Barbara; Poitras, Nancy E; Befano, Brian; Castle, Philip E; Schiffman, Mark

    2018-04-01

    To inform impending postcolposcopy guidelines, this analysis examined the subsequent risk of CIN 3+ among women with a grade lower than CIN 2 (< CIN 2) colposcopy results, taking into account the referring results that brought them to colposcopy and cotest results postcolposcopy. We analyzed 107,005 women from 25 to 65 years old, recommended for colposcopy at Kaiser Permanente Northern California. We estimated absolute risks of CIN 3+ among women: (1) recommended for colposcopy (precolposcopy), (2) following colposcopy and with histology results < CIN 2 (postcolposcopy), and (3) with cotest results 12 months after a < CIN 2 colposcopy (return cotest). After colposcopy showing < CIN 2 (n = 69,790; 87% of the women at colposcopy), the 1-year risk of CIN 3+ was 1.2%, compared with 6.3% at the time of colposcopy recommendation. Negative cotest results 1 year after colposcopy identified a large group (37.1%) of women whose risk of CIN 3+ (i.e., <0.2% at 3 years after postcolposcopy cotest) was comparable with women with normal cytology in the screening population. These risks are consistent with current guidelines recommending repeat cotesting 12 months after colposcopy < CIN 2 and a 3-year return for women with a negative postcolposcopy cotest. Most women are at low risk of subsequent CIN 3+ after a colposcopy showing < CIN 2, especially those who are human papillomavirus-negative postcolposcopy, consistent with current management guidelines for repeat testing intervals. Before the finalizing the upcoming guidelines, we will consider additional rounds of postcolposcopy cotesting.

  16. Anxiety and depression in breast cancer patients at low risk of recurrence compared with the general population: a valid comparison?

    NARCIS (Netherlands)

    Groenvold, M.; Fayers, P. M.; Sprangers, M. A.; Bjorner, J. B.; Klee, M. C.; Aaronson, N. K.; Bech, P.; Mouridsen, H. T.

    1999-01-01

    Breast cancer and its treatment have been associated with psychological morbidity. In this study our aim was to quantify the excess anxiety and depression resulting from breast cancer. We compared 538 newly diagnosed breast cancer patients at low risk of recurrence (87.0% responded) to 872 women

  17. Severe adverse maternal outcomes among low risk women with planned home versus hospital births in the Netherlands: nationwide cohort study

    NARCIS (Netherlands)

    de Jonge, J.; Mesman, J.A.J.M.; Manniën, J.; Zwart, J.J.; van Dillen, J.; van Roosmalen, J.

    2013-01-01

    Objectives: To test the hypothesis that low risk women at the onset of labour with planned home birth have a higher rate of severe acute maternal morbidity than women with planned hospital birth, and to compare the rate of postpartum haemorrhage and manual removal of placenta. Design: Cohort study

  18. Outcome of planned home and planned hospital births in low risk pregnancies: prospective study in midwifery practices in the Netherlands.

    NARCIS (Netherlands)

    Wiegers, T.A.; Keirse, M.J.N.C.; Zee, J. van der; Berghs, G.A.H.

    1996-01-01

    Objective: To investigate the relation between the intended place of birth (home or hospital) and perinatal outcome in women with low risk pregnancies after controlling for parity and social, medical, and obstetric background. Design: Analysis of prospective data from midwives and their clients.

  19. High incidence of pseudotumours after hip resurfacing even in low risk patients; results from an intensified MRI screening protocol.

    NARCIS (Netherlands)

    Weegen, W. van der; Smolders, J.M.; Sijbesma, T.; Hoekstra, H.J.; Brakel, K.; Susante, J.L.C. van

    2013-01-01

    We intensified our screening protocol for the presence of pseudotumours in a consecutive series of patients with a hip resurfacing arthroplasty (HRA), to establish whether we should be alert to the presence of 'silent' pseudotumours. Patients categorised with high risk (11 hips) and low risk (10

  20. Identification of patients with low-risk pulmonary embolism suitable for outpatient treatment using the pulmonary embolism severity index (PESI).

    LENUS (Irish Health Repository)

    McCabe, A

    2013-06-01

    There is increasing evidence that outpatient treatment of patients with low-risk stable pulmonary embolism (PE) is safe, effective and potentially reduces costs. It is not clear how many patients presenting to an Irish Emergency Department (ED) are potentially suitable for outpatient management.

  1. Adverse outcomes in maternity care for women with a low risk profile in The Netherlands: a case series analysis

    NARCIS (Netherlands)

    Martijn, L.; Jacobs, A.; Amelink-Verburg, M.; Wentzel, R.; Buitendijk, S.; Wensing, M.

    2013-01-01

    BACKGROUND: This study aimed to perform a structural analysis of determinants of risk of critical incidents in care for women with a low risk profile at the start of pregnancy with a view on improving patient safety. METHODS: We included 71 critical incidents in primary midwifery care and subsequent

  2. [Adverse outcomes in maternity care for women with a low risk profile in The Netherlands: a case series analysis

    NARCIS (Netherlands)

    Martijn, L.M.; Jacobs, A.; Amelink-Verburg, M.P.; Wentzel, R.; Buitendijk, S.E.; Wensing, M.

    2014-01-01

    BACKGROUND: This study aimed to perform a structural analysis of determinants of risk of critical incidents in care for women with a low risk profile at the start of pregnancy with a view on improving patient safety. METHODS: We included 71 critical incidents in primary midwifery care and subsequent

  3. Evaluating genome-wide association study-identified breast cancer risk variants in African-American women.

    Directory of Open Access Journals (Sweden)

    Jirong Long

    Full Text Available Genome-wide association studies (GWAS, conducted mostly in European or Asian descendants, have identified approximately 67 genetic susceptibility loci for breast cancer. Given the large differences in genetic architecture between the African-ancestry genome and genomes of Asians and Europeans, it is important to investigate these loci in African-ancestry populations. We evaluated index SNPs in all 67 breast cancer susceptibility loci identified to date in our study including up to 3,300 African-American women (1,231 cases and 2,069 controls, recruited in the Southern Community Cohort Study (SCCS and the Nashville Breast Health Study (NBHS. Seven SNPs were statistically significant (P ≤ 0.05 with the risk of overall breast cancer in the same direction as previously reported: rs10069690 (5p15/TERT, rs999737 (14q24/RAD51L1, rs13387042 (2q35/TNP1, rs1219648 (10q26/FGFR2, rs8170 (19p13/BABAM1, rs17817449 (16q12/FTO, and rs13329835 (16q23/DYL2. A marginally significant association (P<0.10 was found for three additional SNPs: rs1045485 (2q33/CASP8, rs4849887 (2q14/INHBB, and rs4808801 (19p13/ELL. Three additional SNPs, including rs1011970 (9p21/CDKN2A/2B, rs941764 (14q32/CCDC88C, and rs17529111 (6q14/FAM46A, showed a significant association in analyses conducted by breast cancer subtype. The risk of breast cancer was elevated with an increasing number of risk variants, as measured by quintile of the genetic risk score, from 1.00 (reference, to 1.75 (1.30-2.37, 1.56 (1.15-2.11, 2.02 (1.50-2.74 and 2.63 (1.96-3.52, respectively, (P = 7.8 × 10(-10. Results from this study highlight the need for large genetic studies in AAs to identify risk variants impacting this population.

  4. Quantifying the Transition from Active Surveillance to Watchful Waiting Among Men with Very Low-risk Prostate Cancer.

    Science.gov (United States)

    Van Hemelrijck, Mieke; Garmo, Hans; Lindhagen, Lars; Bratt, Ola; Stattin, Pär; Adolfsson, Jan

    2017-10-01

    Active surveillance (AS) is commonly used for men with low-risk prostate cancer (PCa). When life expectancy becomes too short for curative treatment to be beneficial, a change from AS to watchful waiting (WW) follows. Little is known about this change since it is rarely documented in medical records. To model transition from AS to WW and how this is affected by age and comorbidity among men with very low-risk PCa. National population-based healthcare registers were used for analysis. Using data on PCa characteristics, age, and comorbidity, a state transition model was created to estimate the probability of changes between predefined treatments to estimate transition from AS to WW. Our estimates indicate that 48% of men with very low-risk PCa starting AS eventually changed to WW over a life course. This proportion increased with age at time of AS initiation. Within 10 yr from start of AS, 10% of men aged 55 yr and 50% of men aged 70 yr with no comorbidity at initiation changed to WW. Our prevalence simulation suggests that the number of men on WW who were previously on AS will eventually stabilise after 30 yr. A limitation is the limited information from clinical follow-up visits (eg, repeat biopsies). We estimated that changes from AS to WW become common among men with very low-risk PCa who are elderly. This potential change to WW should be discussed with men starting on AS. Moreover, our estimates may help in planning health care resources allocated to men on AS, as the transition to WW is associated with lower demands on outpatient resources. Changes from active surveillance to watchful waiting will become more common among men with very low-risk prostate cancer. These observations suggest that patients need to be informed about this potential change before they start on active surveillance. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  5. Quantifying the benefits of achieving or maintaining long-term low risk profile for cardiovascular disease: The Doetinchem Cohort Study.

    Science.gov (United States)

    Hulsegge, Gerben; Smit, Henriëtte A; van der Schouw, Yvonne T; Daviglus, Martha L; Verschuren, W M Monique

    2015-10-01

    Studies investigating the relation between risk profiles and cardiovascular disease have measured risk at baseline only. We investigated maintenance and changes of risk profiles over time and their potential impact on incident cardiovascular disease. Population-based cohort study. Risk factors were measured at baseline (1987-1991) among 5574 cardiovascular disease-free adults aged 20-59 years. They were classified into four risk categories according to smoking status, presence of diabetes and widely accepted cut-off values for blood pressure, total cholesterol/HDL-ratio and body mass index. Categories were subdivided (maintenance, deterioration, improvement) based on risk factor levels at six and 11 years of follow-up. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular disease incidence 5-10 years following the risk-change period were fitted using Cox proportional hazards models. Only 12% of participants were low risk at baseline, and only 7% maintained it. Participants who maintained a low risk profile over 11 years had seven times lower risk of cardiovascular disease (HR: 0.14, 95% CI: 0.05-0.41) than participants with long-term high risk profile, whereas those low risk at baseline whose profile deteriorated had three times lower risk (HR: 0.36, 95% CI: 0.18-0.71). Our results suggest that, within each baseline risk profile group, compared with a stable profile, improving profiles may be associated with up to two-fold lower HRs, and deteriorating profiles with about two-fold higher HRs. Our study, using long-term risk profiles, demonstrates the full benefits of low risk profile. These findings underscore the importance of achieving and maintaining low risk from young adulthood onwards. © The European Society of Cardiology 2014.

  6. Identification of Patients at Very Low Risk of Local Recurrence After Breast-Conserving Surgery

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Sally L., E-mail: ssmith11@bccancer.bc.ca [Radiation Therapy Program and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, British Columbia (Canada); Truong, Pauline T. [Radiation Therapy Program and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, British Columbia (Canada); Lu, Linghong; Lesperance, Mary [Department of Mathematics and Statistics, University of Victoria, Victoria, British Columbia (Canada); Olivotto, Ivo A. [Division of Radiation Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta (Canada)

    2014-07-01

    Purpose: To identify clinical and pathological factors that identify groups of women with stage I breast cancer with a 5-year risk of local recurrence (LR) ≤1.5% after breast-conserving therapy (BCS) plus whole-breast radiation therapy (RT). Methods and Materials: Study subjects were 5974 patients ≥50 years of age whose cancer was diagnosed between 1989 and 2006, and were referred with pT1 pN0 invasive breast cancer treated with BCS and RT. Cases of 5- and 10-year LR were examined using Kaplan-Meier methods. Recursive partitioning analysis was performed in patients treated with and without endocrine therapy to identify combinations of factors associated with a 5-year LR risk ≤1.5%. Results: The median follow-up was 8.61 years. Median age was 63 years of age (range, 50 to 91). Overall 5-year LR was 1.5% (95% confidence interval [CI], 1.2%-1.9%) and 10-year LR was 3.4% (95% CI, 2.8%-4.0%). Of 2830 patients treated with endocrine therapy, patient subsets identified with 5-year LR ≤1.5% included patients with grade 1 histology (n=1038; LR, 0.2%; 95% CI, 0%-0.5%) or grade 2 histology plus ≥60 years of age (n=843; LR, 0.5%; 95% CI, 0%-1.0%). Ten-year LR for these groups were 0.8% (95% CI, 0.1%-1.6%) and 0.9% (95% CI, 0.2%-1.6%), respectively. Of 3144 patients treated without endocrine therapy, patients with grade 1 histology plus clear margins had 5-year LR ≤1.5% (n=821; LR, 0.6%; 95% CI, 0.1%-1.2%). Ten-year LR for this group was 2.2% (95% CI, 1.0%-3.4%). Conclusions: Histologic grade, age, margin status, and use of endocrine therapy identified 45% of a population-based cohort of female patients over age 50 with stage I breast cancer with a 5-year LR risk ≤1.5% after BCS plus RT. Prospective study is needed to evaluate the safety of omitting RT in patients with such a low risk of LR.

  7. Utilization of prostate brachytherapy for low risk prostate cancer: Is the decline overstated?

    Directory of Open Access Journals (Sweden)

    Joseph Safdieh

    2016-08-01

    Full Text Available Purpose : Several prior studies have suggested that brachytherapy utilization has markedly decreased, coinciding with the recent increased utilization of intensity modulated radiation therapy, as well as an increase in urologist-owned centers. We sought to investigate the brachytherapy utilization in a large, hospital-based registry. Material and methods: Men with prostate cancer diagnosed between 2004-2012 and treated with either external beam radiation and/or prostate brachytherapy were abstracted from the National Cancer Database. In order to be included, men had to be clinically staged as T1c-T2aNx-0Mx-0, Gleason 6, PSA ≤ 10.0 ng/ml. Descriptive statistics were used to analyze brachytherapy utilization over time and were compared via χ2. Multivariate logistic regression was used to assess for covariables associated with increased brachytherapy usage. Results : There were 89,413 men included in this study, of which 37,054 (41.6% received only external beam radiation, and 52,089 (58.4% received prostate brachytherapy. The use of brachytherapy declined over time from 62.9% in 2004 to 51.3% in 2012 (p < 0.001. This decline was noted in both academic facilities (60.8% in 2004 to 47.0% in 2012, p < 0.001 as well as in non-academic facilities (63.7% in 2004 to 53.0% in 2012, p < 0.001. The decline was more pronounced in patients who lived closer to treatment facilities than those who lived further. The use of intensity modulated radiation therapy increased during this same time period from 18.4% in 2004 to 38.2% in 2012 (p < 0.001. On multivariate analysis, treatment at an academic center, increasing age, decreasing distance from the treatment center, and years of diagnosis from 2006-2012 were significantly associated with reduced brachytherapy usage. Conclusions : In this hospital-based registry, prostate brachytherapy usage has declined for low risk prostate cancer as intensity modulated radiation therapy usage has increased. However, it still

  8. Auto-segmentation of low-risk clinical target volume for head and neck radiation therapy.

    Science.gov (United States)

    Yang, Jinzhong; Beadle, Beth M; Garden, Adam S; Gunn, Brandon; Rosenthal, David; Ang, Kian; Frank, Steven; Williamson, Ryan; Balter, Peter; Court, Laurence; Dong, Lei

    2014-01-01

    To investigate atlas-based auto-segmentation methods to improve the quality of the delineation of low-risk clinical target volumes (CTVs) of unilateral tonsil cancers. Sixteen patients received intensity modulated radiation therapy for left tonsil tumors. These patients were treated by a total of 8 oncologists, who delineated all contours manually on the planning CT image. We chose 6 of the patients as atlas cases and used atlas-based auto-segmentation to map each the atlas CTV to the other 10 patients (test patients). For each test patient, the final contour was produced by combining the 6 individual segmentations from the atlases using the simultaneous truth and performance level estimation algorithm. In addition, for each test patient, we identified a single atlas that produced deformed contours best matching the physician's manual contours. The auto-segmented contours were compared with the physician's manual contours using the slice-wise Hausdorff distance (HD), the slice-wise Dice similarity coefficient (DSC), and a total volume overlap index. No single atlas consistently produced good results for all 10 test cases. The multiatlas segmentation achieved a good agreement between auto-segmented contours and manual contours, with a median slice-wise HD of 7.4 ± 1.0 mm, median slice-wise DSC of 80.2% ± 5.9%, and total volume overlap of 77.8% ± 3.3% over the 10 test cases. For radiation oncologists who contoured both the test case and one of the atlas cases, the best atlas for a test case had almost always been contoured by the oncologist who had contoured that test case, indicating that individual physician's practice dominated in target delineation and was an important factor in optimal atlas selection. Multiatlas segmentation may improve the quality of CTV delineation in clinical practice for unilateral tonsil cancers. We also showed that individual physician's practice was an important factor in selecting the optimal atlas for atlas-based auto

  9. Joint Attention Development in Low-risk Very Low Birth Weight Infants at Around 18 Months of Age.

    Science.gov (United States)

    Yamaoka, Noriko; Takada, Satoshi

    2016-10-18

    The purpose of this study was to clarify the developmental characteristics of joint attention in very low birth weight (VLBW) infants with a low risk of complications. Section B of the Checklist for Autism in Toddlers (CHAT) was administered to 31 VLBW and 45 normal birth weight (NBW) infants aged 18-22 months, while the sessions were recorded with a video camera. A semi-structured observation scale was developed to assess infants' joint attention from the video footage, and was shown to be reliable. VLBW, compared to NBW, infants showed significantly poorer skills in 2 of 4 items on responding to joint attention, and in 6 of 10 items on initiating joint attention. VLBW infants need more clues in order to produce joint attention. The difficulty was attributed to insufficient verbal and fine motor function skills. Continuous follow-up evaluation is essential for both high-risk and low-risk VLBW infants and their parents.

  10. Thyrotropin Suppressive Therapy for Low-Risk Small Thyroid Cancer: A Propensity Score-Matched Cohort Study.

    Science.gov (United States)

    Park, Suyeon; Kim, Won Gu; Han, Minkyu; Jeon, Min Ji; Kwon, Hyemi; Kim, Mijin; Sung, Tae-Yon; Kim, Tae Yong; Kim, Won Bae; Hong, Suck Joon; Shong, Young Kee

    2017-09-01

    Thyrotropin (TSH) suppression has improved the clinical outcomes of patients with differentiated thyroid cancer (DTC). However, the efficacy of TSH suppressive therapy (TST) is unclear in patients with low-risk DTC. This study aimed to evaluate the efficacy of TST and optimal TSH levels of patients with low-risk DTC. This retrospective propensity score-matched cohort study included DTC patients (n = 446) who underwent lobectomy from 2002 to 2008 with or without TST (TST group and No-TST group). Disease-free survival (DFS) and dynamic risk stratification were compared between both groups using serum TSH levels. Approximately 74% of TST patients and 11% of No-TST patients had suppressed serum TSH levels (<2 mIU/L). The median follow-up period was 8.6 years. During follow-up, the disease recurred in 10 (2.7%) patients, with no significant difference in DFS between the groups (p = 0.63). The proportion of patients with excellent treatment response was similar between the TST (65.2%) and No-TST (64.4%) groups. Incomplete biochemical response was noted in 17.2% of the TST group patients and 9.4% of the No-TST group patients. No significant difference was observed in the DFS between both groups by comparing serum TSH level (p = 0.57). TST did not improve clinical outcomes, and serum TSH levels were not associated with recurrence in patients with low-risk small DTC. No clinical benefits were shown for TSH suppression in low-risk patients who underwent lobectomy. Thus, levothyroxine is not necessary for patients without evidence of hypothyroidism.

  11. Accuracy of simple urine tests for diagnosis of urinary tract infections in low-risk pregnant women

    OpenAIRE

    Feitosa,Danielle Cristina Alves; Silva,Márcia Guimarães da; Parada,Cristina Maria Garcia de Lima

    2009-01-01

    Anatomic and physiological alterations during pregnancy predispose pregnant women to urinary tract infections (UTI). This study aimed to identify the accuracy of the simple urine test for UTI diagnosis in low-risk pregnant women. Diagnostic test performance was conducted in Botucatu, SP, involving 230 pregnant women, between 2006 and 2008. Results showed 10% UTI prevalence. Sensitivity, specificity and accuracy of the simple urine test were 95.6%, 63.3% and 66.5%, respectively, in relation to...

  12. [FRAX® thresholds to identify people with high or low risk of osteoporotic fracture in Spanish female population].

    Science.gov (United States)

    Azagra, Rafael; Roca, Genís; Martín-Sánchez, Juan Carlos; Casado, Enrique; Encabo, Gloria; Zwart, Marta; Aguyé, Amada; Díez-Pérez, Adolf

    2015-01-06

    To detect FRAX(®) threshold levels that identify groups of the population that are at high/low risk of osteoporotic fracture in the Spanish female population using a cost-effective assessment. This is a cohort study. Eight hundred and sixteen women 40-90 years old selected from the FRIDEX cohort with densitometry and risk factors for fracture at baseline who received no treatment for osteoporosis during the 10 year follow-up period and were stratified into 3 groups/levels of fracture risk (low20%) according to the real fracture incidence. The thresholds of FRAX(®) baseline for major osteoporotic fracture were: low riskX-ray absorptiometry (DXA-scan) for FRAX(®)≥ 5 (Intermediate and high risk) to reclassify by FRAX(®) with DXA-scan at high/low risk. These thresholds select 17.5% of women for DXA-scan and 10% for treatment. With these thresholds of FRAX(®), compared with the strategy of opportunistic case finding isolated risk factors, would improve the predictive parameters and reduce 82.5% the DXA-scan, 35.4% osteoporosis prescriptions and 28.7% cost to detect the same number of women who suffer fractures. The use of FRAX ® thresholds identified as high/low risk of osteoporotic fracture in this calibration (FRIDEX model) improve predictive parameters in Spanish women and in a more cost-effective than the traditional model based on the T-score ≤ -2.5 of DXA scan. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  13. [C-section rate in low-risk women: a useful indicator to compare hospitals attending deliveries with different risks].

    Science.gov (United States)

    Librero, Julián; Peiró, Salvador; Belda, Ana; Calabuig, Julia

    2014-01-01

    the C-section rate has been criticized as a performance indicator for not considering that different hospitals manage deliveries with diverse risks. In this work we explore the characteristics of a new indicator restricted to low C-section risk deliveries. retrospective cohort of all births (n=214,611) in all public hospitals during 2005-2010 in the Valencia Region, Spain (source: minimum basic dataset). A low-risk subpopulation consisting of women under-35, no history of c-section, between 37 and 41 gestational weeks, and with a single fetus, with cephalic presentation and normal weight (2500-3999 g) was constructed. We analyzed variability in the new indicator, its correlation with the crude indicator and, using multilevel logistic regression models, the presence of residual risks. a total of 117 589 births (58.4% of the whole deliveries) were identified as low C-section risk. The c-section rate in these women was 11.9% (24.4% for all deliveries) ranging between hospitals from 7.0% to 28.9%. The c-section rate in low-risk and total deliveries correlated strongly (r=0.88). The remaining risks in the population of low risk did not alter the hospital effect on the c-section rate. the percentage of C-section in low risk women include a high volume of deliveries, correlated with the crude indicator and residual risks are not differentially influenced by hospitals, being a useful indicator for monitoring the quality of obstetric care in the National Health System.

  14. Development of quality indicators for low-risk labor care provided by midwives using a RAND-modified Delphi method.

    Science.gov (United States)

    Ueda, Kayo; Ohtera, Shosuke; Kaso, Misato; Nakayama, Takeo

    2017-09-22

    In childbirth, most deliveries are low-risk, defined as spontaneous labor at full term without special high-risk facts or complications, especially in high-resource countries where maternal and perinatal mortality rates are very low. Indeed, the majority of mothers and infants have no serious conditions during labor. However, the quality of care provided is not assured, and performance may vary by birthing facility and provider. The overuse of technology in childbirth in some parts of the world is almost certainly based on assumptions like, "something can go wrong at any minute." There is a need to assess the quality of care provided for mothers and infants in low-risk labor. We aimed to develop specific quality indicators for low-risk labor care provided primarily by midwives in Japan. We used a RAND-modified Delphi method, which integrates evidence review with expert consensus development. The procedure comprises five steps: (1) literature review, including clinical practice guidelines, to extract and develop quality indicator candidates; (2) formation of a multidisciplinary panel; (3) independent panel ratings (Round 1); (4) panel meeting and independent panel ratings (Round 2); and (5) independent panel ratings (Round 3). The three independent panel ratings (Rounds 1-3) were held between July and December 2012. The assembled multidisciplinary panel comprised eight clinicians (two pediatricians, three obstetricians, and three midwives) and three mothers who were nonclinicians. Evidentiary review extracted 166 key recommendations from 32 clinical practice guidelines, and 31 existing quality indicators were added. After excluding duplicate recommendations and quality indicators, the panel discussed 25 candidate indicators. Of these, 18 were adopted, one was modified, six were not adopted, and four were added during the meeting, respectively. We established 23 quality indicators for low-risk labor care provided by midwives in labor units in Japan.

  15. Association of spiritual/religious coping with depressive symptoms in high- and low-risk pregnant women.

    Science.gov (United States)

    Vitorino, Luciano M; Chiaradia, Raíssa; Low, Gail; Cruz, Jonas Preposi; Pargament, Kenneth I; Lucchetti, Alessandra L G; Lucchetti, Giancarlo

    2018-02-01

    To investigate the role of spiritual/religious coping (SRC) on depressive symptoms in high- and low-risk pregnant women. Spiritual/religious coping is associated with physical and mental health outcomes. However, only few studies investigated the role of these strategies during pregnancy and whether low- and high-risk pregnant women have different coping mechanisms. This study is a cross-sectional comparative study. This study included a total of 160 pregnant women, 80 with low-risk pregnancy and 80 with high-risk pregnancy. The Beck Depression Inventory, the brief SRC scale and a structured questionnaire on sociodemographic and obstetric aspects were used. General linear model regression analysis was used to identify the factors associated with positive and negative SRC strategies in both groups of pregnant women. Positive SRC use was high, whereas negative SRC use was low in both groups. Although we found no difference in SRC strategies between the two groups, negative SRC was associated with depression in women with high-risk pregnancy, but not in those with low-risk pregnancy. Furthermore, positive SRC was not associated with depressive symptoms in both groups. Results showed that only the negative SRC strategies of Brazilian women with high-risk pregnancies were associated with worsened mental health outcomes. Healthcare professionals, obstetricians and nurse midwives should focus on the use of negative SRC strategies in their pregnant patients. © 2017 John Wiley & Sons Ltd.

  16. A pilot audit of a protocol for ambulatory investigation of predicted low-risk patients with possible pulmonary embolism.

    Science.gov (United States)

    McDonald, A H; Murphy, R

    2011-09-01

    Patients with possible pulmonary embolism (PE) commonly present to acute medical services. Research has led to the identification of low-risk patients suitable for ambulatory management. We report on a protocol designed to select low-risk patients for ambulatory investigation if confirmatory imaging is not available that day. The protocol was piloted in the Emergency Department and Medical Assessment Area at the Royal Infirmary of Edinburgh. We retrospectively analysed electronic patient records in an open observational audit of all patients managed in the ambulatory arm over five months of use. We analysed 45 patients' records. Of these, 91.1% required imaging to confirm or refute PE, 62.2% received a computed tomography pulmonary angiogram (CTPA). In 25% of patients, PE was confirmed with musculoskeletal pain (22.7%), and respiratory tract infection (15.9%) the next most prevalent diagnoses. Alternative diagnoses was provided by CTPA in 32% of cases. We identified no adverse events or readmissions but individualised follow-up was not attempted. The data from this audit suggests this protocol can be applied to select and manage low-risk patients suitable for ambulatory investigation of possible PE. A larger prospective comparative study would be required to accurately define the safety and effectiveness of this protocol.

  17. Perinatal outcomes of low-risk planned home and hospital births under midwife-led care in Japan.

    Science.gov (United States)

    Hiraizumi, Yoshie; Suzuki, Shunji

    2013-11-01

    It has not been extensively studied whether planned home and planned hospital births under primary midwife-led care increase risk of adverse events among low-risk women in Japan. A retrospective cohort study was performed to compare perinatal outcome between 291 women who were given primary midwife-led care during labor and 217 women who were given standard obstetric shared care. Among 291 women with primary midwife-led care, 168 and 123 chose home deliver and hospital delivery, respectively. Perinatal outcomes included length of labor of 24 h or more, augmentation of labor pains, delivery mode, severe perineal laceration, postpartum hemorrhage of 1000 mL or more, maternal fever of 38°C or more and neonatal asphyxia (Apgar score, home delivery (34 vs 21%, P = 0.011). There were no significant differences in the incidence of adverse perinatal outcomes between women with obstetric shared care and women with primary midwife-led care (regardless of being hospital delivery or home delivery). Approximately one-quarter of low-risk women with primary midwife-led care required obstetric care during labor or postpartum. However, primary midwife-led care during labor at home and hospital for low-risk pregnant women was not associated with adverse perinatal outcomes in Japan. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  18. Results of allogeneic stem cell transplantation in the Spanish MDS registry: prognostic factors for low risk patients.

    Science.gov (United States)

    Díez Campelo, M; Sánchez-Barba, M; de Soria, V Gómez-García; Martino, R; Sanz, G; Insunza, A; Bernal, T; Duarte, R; Amigo, M L; Xicoy, B; Tormo, M; Iniesta, F; Bailén, A; Benlloch, L; Córdoba, I; López-Villar, O; Del Cañizo, M C

    2014-10-01

    Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Data-variant kernel analysis

    CERN Document Server

    Motai, Yuichi

    2015-01-01

    Describes and discusses the variants of kernel analysis methods for data types that have been intensely studied in recent years This book covers kernel analysis topics ranging from the fundamental theory of kernel functions to its applications. The book surveys the current status, popular trends, and developments in kernel analysis studies. The author discusses multiple kernel learning algorithms and how to choose the appropriate kernels during the learning phase. Data-Variant Kernel Analysis is a new pattern analysis framework for different types of data configurations. The chapters include

  20. Setting up low-risk bone marrow transplantation for children with thalassemia may facilitate pediatric cancer care

    Directory of Open Access Journals (Sweden)

    Lawrence B Faulkner

    2013-01-01

    Full Text Available Background: In many South Asian countries there is shortage of centers providing care for pediatric malignancies. This report describes the experience of the Cure2Children Foundation (C2C in supporting, both financially and professionally, the startup of two bone marrow transplant (BMT centers, one in Pakistan and one in India, for the cure of transfusion-dependent thalassemia. Even though transplantation is generally considered as a more complex and advanced step relatively to basic pediatric cancer care, the authors argue that BMT for low-risk thalassemia patients with a matched sibling is a relatively simple procedure amenable to focused training. Materials and Methods: Since 2008 the C2C, an Italian Nongovernmental Organization (NGO, has supported a BMT network in Pakistan. The primary aim of this project was to assess feasibility, outcomes, and costs of matched-related BMT for thalassemia in young low-risk children employing a well established and quite tolerable strategy employed in Italy. This initiative relied primarily on focused training and task-shift strategies within a structured cooperation program. The initial success of that strategy led to its replication in India with 100 total BMTs performed over the past 4 years, 91 of which were for thalassemia major. Results: Low-risk matched-related BMT in children younger than 5 years could deliver a 92% thalassemia-free survival with 100% performance score and no extensive chronic graft versus host disease (GVHD, for an average cost of 10,000 USD per BMT. Within an existing hospital facility, 50,000 USD were sufficient to renovate and fully equip a 2-3 bedded start up BMT unit capable of performing safe low-risk compatible marrow transplantation. Conclusions: In low resource settings matched-related low-risk BMT for thalassemia can be performed with outcomes comparable to richer countries and with a fraction of the costs. Within structured and intensive cooperation, good outcomes can be

  1. GCPII Variants, Paralogs and Orthologs

    Czech Academy of Sciences Publication Activity Database

    Hlouchová, Klára; Navrátil, Václav; Tykvart, Jan; Šácha, Pavel; Konvalinka, Jan

    2012-01-01

    Roč. 19, č. 9 (2012), s. 1316-1322 ISSN 0929-8673 R&D Projects: GA ČR GAP304/12/0847 Institutional research plan: CEZ:AV0Z40550506 Keywords : PSMA * GCPIII * NAALADase L * splice variants * homologs * PSMAL Subject RIV: CE - Biochemistry Impact factor: 4.070, year: 2012

  2. Odontogenic keratocyst: a peripheral variant.

    Science.gov (United States)

    Vij, H; Vij, R; Gupta, V; Sengupta, S

    2011-01-01

    Odontogenic keratocyst, which is developmental in nature, is an intraosseous lesion though on rare occasions it may occur in an extraosseous location. The extraosseous variant is referred to as peripheral odontogenic keratocyst. Though, clinically, peripheral odontogenic keratocyst resembles the gingival cyst of adults, it has histologic features that are pathognomonic of odontogenic keratocyst. This article presents a case of this uncommon entity.

  3. Swine Influenza/Variant Influenza Viruses

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Pandemic Other Information on Swine Influenza/Variant Influenza Virus Language: English (US) Español Recommend ...

  4. Oxytocin and dystocia as risk factors for adverse birth outcomes: a cohort of low-risk nulliparous women.

    Science.gov (United States)

    Bernitz, Stine; Øian, Pål; Rolland, Rune; Sandvik, Leiv; Blix, Ellen

    2014-03-01

    augmented and not augmented women without dystocia were compared to investigate associations between oxytocin and adverse birth outcomes. Augmented women with and without dystocia were compared, to investigate associations between dystocia and adverse birth outcomes. a cohort of low-risk nulliparous women originally included in a randomised controlled trial. the Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Norway. the study population consists of 747 well defined low-risk women. incidence of oxytocin augmentation, and associations between dystocia and augmentation, and mode of delivery, transfer of newborns to the intensive care unit, episiotomy and postpartum haemorrhage. of all participants 327 (43.8%) were augmented with oxytocin of which 139 (42.5%) did not fulfil the criteria for dystocia. Analyses adjusted for possible confounders found that women without dystocia had an increased risk of instrumental vaginal birth (OR 3.73, CI 1.93-7.21) and episiotomy (OR 2.47, CI 1.38-4.39) if augmented with oxytocin. Augmented women had longer active phase if vaginally delivered and longer labours if delivered by caesarean section if having dystocia. Among women without dystocia, those augmented had higher body mass index, gave birth to heavier babies, had longer labours if vaginally delivered and had epidural analgesia more often compared to women not augmented. in low-risk nulliparous without dystocia, we found an association between the use of oxytocin and an increased risk of instrumental vaginal birth and episiotomy. careful attention should be paid to criteria for labour progression and guidelines for oxytocin augmentation to avoid unnecessary use. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Physiologic partograph to improve birth safety and outcomes among low-risk, nulliparous women with spontaneous labor onset

    Science.gov (United States)

    Neal, Jeremy L.; Lowe, Nancy K.

    2011-01-01

    Oxytocin augmentation and cesarean rates among low-risk, term, nulliparous women with a spontaneous onset of labor in the United States approximate 50% and 26.5%, respectively. This indicates that the quality of obstetrical care is much less than optimal in this nation. Exorbitant oxytocin use, the intervention most commonly associated with preventable adverse perinatal outcomes, jeopardizes birth safety while the high cesarean rate in this high-volume group compromises population health and increases health care costs. Dystocia, characterized by the slow, abnormal progression of labor, is the most commonly reported indication for primary cesareans, accounting directly for approximately 50% of all nulliparous cesareans and indirectly for most repeat cesareans. Diagnoses of dystocia are most often based on ambiguously defined delays in cervical dilation beyond which labor augmentation is deemed justified. Dystocia is known to be over-diagnosed which undoubtedly contributes to contemporary oxytocin augmentation and primary cesarean rates. Labor attendants would benefit from an evidence-based framework for homogenous labor assessment. To this end, we present a physiologically-based partograph for `in-hospital' use in assessing the labors of low-risk, term, nulliparous women with spontaneous labor onset. This tool incorporates several evidence-based labor principles that combine to give needed clinical meaning to `dystocia' as a diagnosis. It is hypothesized that our partograph will safely limit diagnoses of dystocia to only the slowest 10% of low-risk, nulliparous women. This should, in turn, safe-guard against unnecessary, injudicious, and potentially harmful use of oxytocin when labor is already adequately progressing while also indicating when its use may be justified. We further hypothesize that cesareans performed for dystocia in this population will decrease by ≥ 50%. No significant influence on other labor process or labor outcome variables is expected with

  6. Safety and cost benefit of an ambulatory program for patients with low-risk neutropenic fever at an Australian centre.

    Science.gov (United States)

    Teh, Benjamin W; Brown, Christine; Joyce, Trish; Worth, Leon J; Slavin, Monica A; Thursky, Karin A

    2018-03-01

    Neutropenic fever (NF) is a common complication of cancer chemotherapy. Patients at low risk of medical complications from NF can be identified using a validated risk assessment and managed in an outpatient setting. This is a new model of care for Australia. This study described the implementation of a sustainable ambulatory program for NF at a tertiary cancer centre over a 12-month period. Peter MacCallum Cancer Centre introduced an ambulatory care program in 2014, which identified low-risk NF patients, promoted early de-escalation to oral antibiotics, and early discharge to a nurse-led ambulatory program. Patients prospectively enrolled in the ambulatory program were compared with a historical-matched cohort of patients from 2011 for analysis. Patient demographics, clinical variables (cancer type, recent chemotherapy, treatment intent, site of presentation) and outcomes were collected and compared. Total cost of inpatient admissions was determined from diagnosis-related group (DRG) codes and applied to both the prospective and historical cohorts to allow comparisons. Twenty-five patients were managed in the first year of this program with a reduction in hospital median length of stay from 4.0 to 1.1 days and admission cost from Australian dollars ($AUD) 8580 to $AUD2360 compared to the historical cohort. Offsetting salary costs, the ambulatory program had a net cost benefit of $AUD 71895. Readmission for fever was infrequent (8.0%), and no deaths were reported. Of relevance to hospitals providing cancer care, feasibility, safety, and cost benefits of an ambulatory program for low-risk NF patients have been demonstrated.

  7. Pattern recognition and functional neuroimaging help to discriminate healthy adolescents at risk for mood disorders from low risk adolescents.

    Science.gov (United States)

    Mourão-Miranda, Janaina; Oliveira, Leticia; Ladouceur, Cecile D; Marquand, Andre; Brammer, Michael; Birmaher, Boris; Axelson, David; Phillips, Mary L

    2012-01-01

    There are no known biological measures that accurately predict future development of psychiatric disorders in individual at-risk adolescents. We investigated whether machine learning and fMRI could help to: 1. differentiate healthy adolescents genetically at-risk for bipolar disorder and other Axis I psychiatric disorders from healthy adolescents at low risk of developing these disorders; 2. identify those healthy genetically at-risk adolescents who were most likely to develop future Axis I disorders. 16 healthy offspring genetically at risk for bipolar disorder and other Axis I disorders by virtue of having a parent with bipolar disorder and 16 healthy, age- and gender-matched low-risk offspring of healthy parents with no history of psychiatric disorders (12-17 year-olds) performed two emotional face gender-labeling tasks (happy/neutral; fearful/neutral) during fMRI. We used Gaussian Process Classifiers (GPC), a machine learning approach that assigns a predictive probability of group membership to an individual person, to differentiate groups and to identify those at-risk adolescents most likely to develop future Axis I disorders. Using GPC, activity to neutral faces presented during the happy experiment accurately and significantly differentiated groups, achieving 75% accuracy (sensitivity = 75%, specificity = 75%). Furthermore, predictive probabilities were significantly higher for those at-risk adolescents who subsequently developed an Axis I disorder than for those at-risk adolescents remaining healthy at follow-up. We show that a combination of two promising techniques, machine learning and neuroimaging, not only discriminates healthy low-risk from healthy adolescents genetically at-risk for Axis I disorders, but may ultimately help to predict which at-risk adolescents subsequently develop these disorders.

  8. Retrospective comparison of the Low Risk Ankle Rules and the Ottawa Ankle Rules in a pediatric population.

    Science.gov (United States)

    Ellenbogen, Amy L; Rice, Amy L; Vyas, Pranav

    2017-09-01

    A recent multicenter prospective Canadian study presented prospective evidence supporting the Low Risk Ankle Rules (LRAR) as a means of reducing the number of ankle radiographs ordered for children presenting with an ankle injury while maintaining nearly 100% sensitivity. This is in contrast to a previous prospective study which showed that this rule yielded only 87% sensitivity. It is important to further investigate the LRAR and compare them with the already validated Ottawa Ankle Rules (OAR) to potentially curb healthcare costs and decrease unnecessary radiation exposure without compromising diagnostic accuracy. We conducted a retrospective chart review of 980 qualifying patients ages 12months to 18years presenting with ankle injury to a commonly staffed 310 bed children's hospital and auxiliary site pediatric emergency department. There were 28 high-risk fractures identified. The Ottawa Ankle Rules had a sensitivity of 100% (95% CI 87.7-100), specificity of 33.1% (95% CI 30.1-36.2), and would have reduced the number of ankle radiographs ordered by 32.1%. The Low Risk Ankle Rules had a sensitivity of 85.7% (95% CI 85.7-96), specificity of 64.9% (95% CI 61.8-68), and would have reduced the number of ankle radiographs ordered by 63.1%. The latter rule missed 4 high-risk fractures. The Low Risk Ankle Rules may not be sensitive enough for use in Pediatric Emergency Departments, while the Ottawa Ankle Rules again demonstrated 100% sensitivity. Further research on ways to implement the Ottawa Ankle Rules and maximize its ability to decrease wait times, healthcare costs, and improve patient satisfaction are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Relationship between polycythemia and in-hospital mortality in chronic obstructive pulmonary disease patients with low-risk pulmonary embolism

    Science.gov (United States)

    Guo, Lu; Chughtai, Aamer Rasheed; Jiang, Hongli; Gao, Lingyun; Yang, Yan; Yang, Yang; Liu, Yuejian

    2016-01-01

    Backgrounds Pulmonary embolism (PE) is frequent in subjects with chronic obstructive pulmonary disease (COPD) and associated with high mortality. This multi-center retrospective study was performed to investigate if secondary polycythemia is associated with in-hospital mortality in COPD patients with low-risk PE. Methods We identified COPD patients with proven PE between October, 2005 and October, 2015. Patients in risk classes III–V on the basis of the PESI score were excluded. We extracted demographic, clinical and laboratory information at the time of admission from medical records. All subjects were followed until hospital discharge to identify all-cause mortality. Results We enrolled 629 consecutive patients with COPD and PE at low risk: 132 of them (21.0%) with and 497 (79.0%) without secondary polycythemia. Compared with those without polycythemia, the polycythemia group had significantly lower forced expiratory volume in one second (FEV1) level (0.9±0.3 vs. 1.4±0.5, P=0.000), lower PaO2 and SpO2 as well as higher PaCO2 (P=0.03, P=0.03 and P=0.000, respectively). COPD patients with polycythemia had a higher proportion of arrhythmia in electrocardiogram (ECG) (49.5% vs. 35.7%, P=0.02), a longer hospital duration time (15.3±10.1 vs. 9.7±9.1, P=0.001), a higher mechanical ventilation rate (noninvasive and invasive, 51.7% vs. 30.3%, P=0.04 and 31.0% vs. 7.9%, P=0.04, respectively), and a higher in-hospital mortality (12.1% vs. 6.6%, P=0.04). Multivariate logistic regression analysis revealed that polycythemia was associated with mortality in COPD patients with low-risk PE (adjusted OR 1.11; 95% CI, 1.04–1.66). Conclusions Polycythemia is an independent risk factor for all-cause in-hospital mortality in COPD patients with PE at low risk. PMID:28066591

  10. Clinical governance and research ethics as barriers to UK low-risk population-based health research?

    Directory of Open Access Journals (Sweden)

    Douglas Flora

    2008-11-01

    Full Text Available Abstract Background Since the Helsinki Declaration was introduced in 1964 as a code of practice for clinical research, it has generally been agreed that research governance is also needed in the field of public health and health promotion research. Recently, a range of factors led to the development of more stringent bureaucratic procedures, governing the conduct of low-risk population-based health research in the United Kingdom. Methods Our paper highlights a case study of the application process to medical research ethics committees in the United Kingdom for a study of the promotion of physical activity by health care providers. The case study presented here is an illustration of the challenges in conducting low-risk population-based health research. Results Our mixed-methods approach involved a questionnaire survey of and semi-structured interviews with health professionals (who were all healthy volunteers. Since our study does not involve the participation of either patients or the general population, one would expect the application to the relevant research ethics committees to be a formality. This proved not to be the case! Conclusion Research ethics committees could be counter-productive, rather than protecting the vulnerable in the research process, they can stifle low-risk population-based health research. Research ethics in health services research is first and foremost the responsibility of the researcher(s, and we need to learn to trust health service researchers again. The burden of current research governance regulation to address the perceived ethical problems is neither appropriate nor adequate. Senior researchers/academics need to educate and train students and junior researchers in the area of research ethics, whilst at the same time reducing pressures on them that lead to unethical research, such as commercial funding, inappropriate government interference and the pressure to publish. We propose that non-invasive low-risk

  11. Biologico-clinical significance of DNMT3A variants expression in acute myeloid leukemia.

    Science.gov (United States)

    Lin, Na; Fu, Wei; Zhao, Chen; Li, Bixin; Yan, Xiaojing; Li, Yan

    2017-12-09

    DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays important roles in the pathogenesis of acute myeloid leukemia. However, the expression status of DNMT3A variants in acute myeloid leukemia remains obscure. This study aimed to assess the expression levels of alternative splicing of DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A variants gene expression were assessed, measuring their effects on cell proliferation. In addition, the expression of DNMT3A variants were evaluated in acute myeloid leukemia patients. Four DNMT3A variants were identified, with DNMT3A1 and DNMT3A2V found to be dominant in acute myeloid leukemia cell lines. Moreover, DNMT3A2V overexpression delayed cell proliferation; while, DNMT3A2V R882H mutation promoted cell proliferation. Further, DNMT3A1 and DNMT3A2V were detected in newly diagnosed acute myeloid leukemia (AML) patients and controls with non-malignant hematological disease, with DNMT3A2V significantly up-regulated in AML patients. The main transcript switched from DNMT3A1 to DNMT3A2V in some patients, especially the low risk group based on the NCCN 2016 guidelines. These findings suggest that DNMT3A1 and DNMT3A2V are the main variants in acute myeloid leukemia with different clinical association, and might play important roles in the pathophysiology of acute myeloid leukemia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Dopaminergic variants in siblings at high risk for autism: Associations with initiating joint attention.

    Science.gov (United States)

    Gangi, Devon N; Messinger, Daniel S; Martin, Eden R; Cuccaro, Michael L

    2016-11-01

    Younger siblings of children with autism spectrum disorder (ASD; high-risk siblings) exhibit lower levels of initiating joint attention (IJA; sharing an object or experience with a social partner through gaze and/or gesture) than low-risk siblings of children without ASD. However, high-risk siblings also exhibit substantial variability in this domain. The neurotransmitter dopamine is linked to brain areas associated with reward, motivation, and attention, and common dopaminergic variants have been associated with attention difficulties. We examined whether these common dopaminergic variants, DRD4 and DRD2, explain variability in IJA in high-risk (n = 55) and low-risk (n = 38) siblings. IJA was assessed in the first year during a semi-structured interaction with an examiner. DRD4 and DRD2 genotypes were coded according to associated dopaminergic functioning to create a gene score, with higher scores indicating more genotypes associated with less efficient dopaminergic functioning. Higher dopamine gene scores (indicative of less efficient dopaminergic functioning) were associated with lower levels of IJA in the first year for high-risk siblings, while the opposite pattern emerged in low-risk siblings. Findings suggest differential susceptibility-IJA was differentially associated with dopaminergic functioning depending on familial ASD risk. Understanding genes linked to ASD-relevant behaviors in high-risk siblings will aid in early identification of children at greatest risk for difficulties in these behavioral domains, facilitating targeted prevention and intervention. Autism Res 2016, 9: 1142-1150. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  13. Coronary artery anatomy and variants

    Energy Technology Data Exchange (ETDEWEB)

    Malago, Roberto; Pezzato, Andrea; Barbiani, Camilla; Alfonsi, Ugolino; Nicoli, Lisa; Caliari, Giuliana; Pozzi Mucelli, Roberto [Policlinico G.B. Rossi, University of Verona, Department of Radiology, Verona (Italy)

    2011-12-15

    Variants and congenital anomalies of the coronary arteries are usually asymptomatic, but may present with severe chest pain or cardiac arrest. The introduction of multidetector CT coronary angiography (MDCT-CA) allows the detection of significant coronary artery stenosis. Improved performance with isotropic spatial resolution and higher temporal resolution provides a valid alternative to conventional coronary angiography (CCA) in many patients. MDCT-CA is now considered the ideal tool for three-dimensional visualization of the complex and tortuous anatomy of the coronary arteries. With multiplanar and volume-rendered reconstructions, MDCT-CA may even outperform CCA in determining the relative position of vessels, thus providing a better view of the coronary vascular anatomy. The purpose of this review is to describe the normal anatomy of the coronary arteries and their main variants based on MDCT-CA with appropriate reconstructions. (orig.)

  14. p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare-Stevenson mice

    Czech Academy of Sciences Publication Activity Database

    Wang, Y.L.; Zhou, X.Y.; Oberoi, K.; Phelps, R.; Couwenhoven, R.; Sun, M.; Rezza, A.; Holmes, G.; Percival, C.J.; Friedenthal, J.; Krejčí, Pavel

    2012-01-01

    Roč. 122, č. 6 (2012), s. 2153-2164 ISSN 0021-9738 Institutional support: RVO:68081707 Keywords : CUTIS-GYRATA-SYNDROME * ACTIVATED PROTEIN-KINASE * GROWTH-FACTOR RECEPTOR-2 Subject RIV: BO - Biophysics Impact factor: 12.812, year: 2012

  15. Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling

    Czech Academy of Sciences Publication Activity Database

    Merrill, A.E.; Sarukhanov, A.; Krejčí, Pavel; Idoni, B.; Carmacho, N.; Estrada, K.D.; Lyons, K.M.; Deixler, H.; Robinson, H.; Chitayat, D.; Curry, C.J.; Lachman, R.S.; Wilcox, W.R.; Krakow, D.

    2012-01-01

    Roč. 90, č. 3 (2012), s. 550-557 ISSN 0002-9297 Grant - others:-(US) HD22657; -(US) 5 P30 DE020750-02 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : APERT- SYNDROME * LADD SYNDROME * GROWTH Subject RIV: BO - Biophysics Impact factor: 11.202, year: 2012

  16. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  17. Defining the implant treatment volume for patients with low risk prostate cancer: does the anterior base need to be treated?

    International Nuclear Information System (INIS)

    D'Amico, Anthony V.; Davis, Ann; Vargas, Sara O.; Renshaw, Andrew A.; Jiroutek, Michael; Richie, Jerome P.

    1999-01-01

    Purpose: An increased incidence of acute urinary retention has been reported after interstitial prostate radiation therapy when the anterior base of the prostate gland receives 100% of the prescription dose. The frequency of prostate cancer in this location as a function of the pre-treatment prostate specific antigen (PSA), biopsy Gleason score, and 1992 American Joint Commission on Cancer Staging (AJCC) was determined. Methods and Materials: One hundred four men treated at the Brigham and Women's Hospital with radical prostatectomy for clinically localized prostate cancer between 1995-1996 comprised the study population. Prostatectomy specimens were whole mounted and the location of each tumor foci enumerated. Results: Of 269 foci of prostate cancer found in 39 low-risk prostate cancer patients (PSA 1c,2a ), a single focus (0.37%) was noted in the anterior base. Conversely, 20/355 (5.6%) and 18/251 (7.2%) tumor foci were noted in the anterior base in 43 patients with intermediate risk and 24 patients with high-risk disease, respectively. Conclusions: A new definition of the treatment volume excluding the anterior base for low-risk prostate cancer patients may be justified

  18. Applying decision tree for identification of a low risk population for type 2 diabetes. Tehran Lipid and Glucose Study.

    Science.gov (United States)

    Ramezankhani, Azra; Pournik, Omid; Shahrabi, Jamal; Khalili, Davood; Azizi, Fereidoun; Hadaegh, Farzad

    2014-09-01

    The aim of this study was to create a prediction model using data mining approach to identify low risk individuals for incidence of type 2 diabetes, using the Tehran Lipid and Glucose Study (TLGS) database. For a 6647 population without diabetes, aged ≥20 years, followed for 12 years, a prediction model was developed using classification by the decision tree technique. Seven hundred and twenty-nine (11%) diabetes cases occurred during the follow-up. Predictor variables were selected from demographic characteristics, smoking status, medical and drug history and laboratory measures. We developed the predictive models by decision tree using 60 input variables and one output variable. The overall classification accuracy was 90.5%, with 31.1% sensitivity, 97.9% specificity; and for the subjects without diabetes, precision and f-measure were 92% and 0.95, respectively. The identified variables included fasting plasma glucose, body mass index, triglycerides, mean arterial blood pressure, family history of diabetes, educational level and job status. In conclusion, decision tree analysis, using routine demographic, clinical, anthropometric and laboratory measurements, created a simple tool to predict individuals at low risk for type 2 diabetes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Infant Feeding Attitudes and Practices of Spanish Low-Risk Expectant Women Using the IIFAS (Iowa Infant Feeding Attitude Scale).

    Science.gov (United States)

    Cotelo, María Del Carmen Suárez; Movilla-Fernández, María Jesús; Pita-García, Paula; Novío, Silvia

    2018-04-22

    The Iowa Infant Feeding Attitude Scale (IIFAS) has been shown to have good psychometric properties for English-speaking populations, but it has not been validated among low-risk pregnant women in Spain. The aim of this study was to assess the reliability and validity of the translated version of the IIFAS in order to examine infant feeding attitudes in Spanish women with an uncomplicated pregnancy. Low-risk expectant women ( n = 297) were recruited from eight primary public health care centres in Galicia (Spain). Questionnaires including both socio-demographic and breastfeeding characteristics and items about infant feeding were administered during the third trimester. Participants were contacted by telephone during the postpartum period to obtain information regarding their infant feeding status. Prediction validity and internal consistency were assessed. The translated IIFAS (69.76 ± 7.75), which had good psychometric properties (Cronbach's alpha = 0.785; area under the curve (AUC) of the receiver operating characteristic (ROC) curve = 0.841, CI 95% = 0.735⁻0.948), showed more positive attitudes towards breastfeeding than towards formula feeding, especially among mothers who intended to exclusively breastfeed. This scale was also useful for inferring the intent to breastfeed and duration of breastfeeding. This study provides evidence that the IIFAS is a reliable and valid tool for assessing infant feeding attitudes in Spanish women with an uncomplicated pregnancy.

  20. Results of implementation of a hospital-based strategy to reduce cesarean delivery among low-risk women in Canada.

    Science.gov (United States)

    Shoemaker, Esther S; Bourgeault, Ivy L; Cameron, Carol; Graham, Ian D; Hutton, Eileen K

    2017-11-01

    To assess the cesarean delivery (CD) rate among low-risk pregnancies before and after implementation of a hospital-based program in Canada. A prospective before-and-after study was conducted to assess the effects of the CARE (CAesarean REduction) strategy, which was developed and implemented at Markham Stouffville Hospital, Toronto, ON, Canada, in 2010 to reduce CD among low-risk women. Hospital records were reviewed to identify changes in the proportions of CD performed during 12 months (April 2009-March 2010) before implementation of the CARE strategy versus 12 months after implementation (April 2012-March 2013) at Markham Stouffville Hospital and 36 hospitals of the same level in the same province. At the intervention hospital, 30.3% (964/3181) of women underwent CD in 2009-2010, compared with 26.4% (803/3045) in 2012-2013 (difference -3.9%, PImplementation of the CARE strategy reduced rates of CD among the target population. © 2017 International Federation of Gynecology and Obstetrics.

  1. Comparison of frequency of obesity in high risk non diabetic young individuals with low risk non diabetic young individuals

    International Nuclear Information System (INIS)

    Shaikh, M.A.; Kumar, R.; Ghori, R.A.

    2011-01-01

    Objective: To assess the body mass index and waist circumferences of high risk non diabetic young individuals and compare them with low risk non diabetic young individuals. Method: A cross sectional, case control comparative study was conducted in the department of medicine, LUMHS from January 2008 to March 2009. Five hundred individuals 20-40 years of age were selected and divided into two groups i.e. Group A: high risk (250 individuals) and Group B: low risk (250 individuals) on the basis of same age and gender. Group A included those who had positive family history of type 2 DM in first degree relatives while group B had no family history of type 2 DM in first degree relatives. The blood pressure, BMI and Waist Circumference was measured and Fasting Blood Sugar was estimated in each individual. In each group 125 (50%) were males and 125 (50%) were females. Results: In group A 58% and in group B 28.8% individuals represented raised BMI whereas 42% in group A and 36% in group B individuals showed an increased waist circumference. Mean fasting blood glucose was significantly higher in Group A than in Group B (P=0.001). Conclusion: Impaired Fasting Glucose is strongly associated with family history of type 2 diabetes mellitus. Presence of obesity specially in high risk non-diabetic young individuals emphasize the need for routine health screening for early institution of preventive measures. (author)

  2. Validity Assessment of Low-risk SCORE Function and SCORE Function Calibrated to the Spanish Population in the FRESCO Cohorts.

    Science.gov (United States)

    Baena-Díez, José Miguel; Subirana, Isaac; Ramos, Rafael; Gómez de la Cámara, Agustín; Elosua, Roberto; Vila, Joan; Marín-Ibáñez, Alejandro; Guembe, María Jesús; Rigo, Fernando; Tormo-Díaz, María José; Moreno-Iribas, Conchi; Cabré, Joan Josep; Segura, Antonio; Lapetra, José; Quesada, Miquel; Medrano, María José; González-Diego, Paulino; Frontera, Guillem; Gavrila, Diana; Ardanaz, Eva; Basora, Josep; García, José María; García-Lareo, Manel; Gutiérrez-Fuentes, José Antonio; Mayoral, Eduardo; Sala, Joan; Dégano, Irene R; Francès, Albert; Castell, Conxa; Grau, María; Marrugat, Jaume

    2018-04-01

    To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  3. The reliability of transabdominal cervical length measurement in a low-risk obstetric population: Comparison with transvaginal measurement.

    Science.gov (United States)

    Peng, Cheng-Ran; Chen, Chie-Pein; Wang, Kuo-Gon; Wang, Liang-Kai; Chen, Chen-Yu; Chen, Yi-Yung

    2015-04-01

    To determine the correlation between transabdominal (TA) and transvaginal (TV) cervical length measurement in a low-risk obstetric population in Taiwan. Women with a singleton pregnancy between 20 weeks and 24 weeks of gestation underwent postvoid TA and TV cervical length measurements. Differences between the measurements obtained using the two methods were evaluated. Two hundred and five women agreed to participate in the study. Paired TA and TV measurements were obtained in 174 women. The mean TA cervical length was 36.0 ± 4.9 mm and the mean TV cervical length was 37.6 ± 5.4 mm. The mean TA cervical length was shorter than the mean TV cervical length by 1.6 mm. The 5(th) percentile of TA and TV cervical length was 29 mm and 29.1 mm, respectively. The discrepancies between the two methods were not significantly correlated with maternal body mass index (BMI). All women with TV cervical length women in the present study, and the TA cervical length was closely correlated with the TV cervical length. The use of TA ultrasound could be an effective initial tool for cervical length screening in low-risk pregnant women. TA cervical length TV ultrasound. Copyright © 2015. Published by Elsevier B.V.

  4. Infant Feeding Attitudes and Practices of Spanish Low-Risk Expectant Women Using the IIFAS (Iowa Infant Feeding Attitude Scale

    Directory of Open Access Journals (Sweden)

    María del Carmen Suárez Cotelo

    2018-04-01

    Full Text Available The Iowa Infant Feeding Attitude Scale (IIFAS has been shown to have good psychometric properties for English-speaking populations, but it has not been validated among low-risk pregnant women in Spain. The aim of this study was to assess the reliability and validity of the translated version of the IIFAS in order to examine infant feeding attitudes in Spanish women with an uncomplicated pregnancy. Low-risk expectant women (n = 297 were recruited from eight primary public health care centres in Galicia (Spain. Questionnaires including both socio-demographic and breastfeeding characteristics and items about infant feeding were administered during the third trimester. Participants were contacted by telephone during the postpartum period to obtain information regarding their infant feeding status. Prediction validity and internal consistency were assessed. The translated IIFAS (69.76 ± 7.75, which had good psychometric properties (Cronbach’s alpha = 0.785; area under the curve (AUC of the receiver operating characteristic (ROC curve = 0.841, CI95% = 0.735–0.948, showed more positive attitudes towards breastfeeding than towards formula feeding, especially among mothers who intended to exclusively breastfeed. This scale was also useful for inferring the intent to breastfeed and duration of breastfeeding. This study provides evidence that the IIFAS is a reliable and valid tool for assessing infant feeding attitudes in Spanish women with an uncomplicated pregnancy.

  5. The impact of ultrasonographic placental architecture on antenatal course, labor and delivery in a low-risk primigravid population.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2012-02-01

    OBJECTIVE: To ascertain the impact of placental architecture on antenatal course and labor delivery in a low-risk primigravid population. METHODS: This study involves prospective recruitment of 1011 low-risk primigravids with placental ultrasound at 22?24 weeks and 36 weeks. Detailed postnatal review of all mothers and infants was undertaken. Retrospective analysis of ultrasound and clinical outcome data was performed. RESULTS: Eight hundred ten women with complete outcome data were available. Anterior placentation was statistically associated with intrauterine growth restriction (IUGR) and preterm birth and fundal placentation was significantly associated with a higher incidence of pregnancy-induced hypertension and infants with a birthweight less than the 9th centile. Placental infarcts in the third trimester was significantly increased in cases complicated by pre-eclampsia (PET) and in cases with fetal acidosis. Placental calcification was associated a 40-fold increase in the incidence of IUGR. Placental lakes in the second trimester were more prevalent in patients with threatened miscarriage. Increased placental thickness was associated with a higher rate of fetal acidosis. The Grannum grade of the placenta was higher with threatened first or second trimester loss, PET and in infants born less than 9th centile for gestation. CONCLUSION: Placental site and architecture impact on the incidence of maternal and fetal disease.

  6. Characterization of form variants of Xenorhabdus luminescens.

    Science.gov (United States)

    Gerritsen, L J; de Raay, G; Smits, P H

    1992-01-01

    From Xenorhabdus luminescens XE-87.3 four variants were isolated. One, which produced a red pigment and antibiotics, was luminescent, and could take up dye from culture media, was considered the primary form (XE-red). A pink-pigmented variant (XE-pink) differed from the primary form only in pigmentation and uptake of dye. Of the two other variants, one produced a yellow pigment and fewer antibiotics (XE-yellow), while the other did not produce a pigment or antibiotics (XE-white). Both were less luminescent, did not take up dye, and had small cell and colony sizes. These two variants were very unstable and shifted to the primary form after 3 to 5 days. It was not possible to separate the primary form and the white variant completely; subcultures of one colony always contained a few colonies of the other variant. The white variant was also found in several other X. luminescens strains. DNA fingerprints showed that all four variants are genetically identical and are therefore derivatives of the same parent. Protein patterns revealed a few differences among the four variants. None of the variants could be considered the secondary form. The pathogenicity of the variants decreased in the following order: XE-red, XE-pink, XE-yellow, and XE-white. The mechanism and function of this variability are discussed. Images PMID:1622273

  7. Human Papillomavirus - Prevalence of High-Risk and Low-Risk Types among Females Aged 14-59 Years, National Health and ...

    Science.gov (United States)

    ... Archive Data & Statistics Sexually Transmitted Diseases Figure 45. Human Papillomavirus — Prevalence of High-risk and Low-risk ... on the STD Data and Statistics page . * HPV = human papillomavirus. NOTE: Error bars indicate 95% confidence interval. ...

  8. Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Sinilnikova, Olga M; McGuffog, Lesley

    2009-01-01

    Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 an...

  9. Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Antoniou, Antonis C.; Sinilnikova, Olga M.; McGuffog, Lesley; Healey, Sue; Nevanlinna, Heli; Heikkinen, Tuomas; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Neuhausen, Susan L.; Ding, Yuan C.; Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary; Peterlongo, Paolo; Peissel, Bernard; Bonanni, Bernardo; Viel, Alessandra; Bernard, Loris; Radice, Paolo; Szabo, Csilla I.; Foretova, Lenka; Zikan, Michal; Claes, Kathleen; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Lejbkowicz, Flavio; Andrulis, Irene L.; Ozcelik, Hilmi; Glendon, Gord; Gerdes, Anne-Marie; Thomassen, Mads; Sunde, Lone; Caligo, Maria A.; Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Kaufman, Bella; Dagan, Efrat; Baruch, Ruth Gershoni; Friedman, Eitan; Harbst, Katja; Barbany-Bustinza, Gisela; Rantala, Johanna; Ehrencrona, Hans; Karlsson, Per; Domchek, Susan M.; Nathanson, Katherine L.; Osorio, Ana; Blanco, Ignacio; Lasa, Adriana; Beniez, Javier; Hamann, Ute; Hogervorst, Frans B. L.; Rookus, Matti A.; Collee, J. Margriet; Devilee, Peter; Ligtenberg, Marjolijn J.; van der Luijt, Rob B.; Aalfs, Cora M.; Waisfisz, Quinten; Wijnen, Juul; van Roozendaal, Cornelis E. P.; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Rosalind; Izatt, Louise; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Cole, Trevor; Hodgson, Shirley; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Buecher, Bruno; Leone, Melanie; Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Caron, Olivier; Lenoir, Gilbert M.; Sevenet, Nicolas; Longy, Michel; Ferrer, Sandra Fert; Prieur, Fabienne; Goldgar, David; Miron, Alexander; John, Esther M.; Buys, Saundra S.; Daly, Mary B.; Hopper, John L.; Terry, Mary Beth; Yassin, Yosuf; Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine; Hansen, Thomas v O.; Barkardottir, Rosa Bjork; Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth; Piedmonte, Marion; Rodriguez, Gustavo C.; Wakeley, Katie; Boggess, John F.; Basil, Jack; Schwartz, Peter E.; Blank, Stephanie V.; Toland, Amanda E.; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny N.; Allavena, Anna; Schmutzler, Rita K.; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Niederacher, Dieter; Deissler, Helmut; Fiebig, Britta; Suttner, Christian; Schoenuchner, Ines; Gadzicki, Dorothea; Caldes, Trinidad; de la Hoya, Miguel; Pooley, Karen A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Gill, Mona; Collins, Lucine; Gokgoz, Nalan; Selander, Teresa; Weerasooriya, Nayana; H, F. B. L.; Verhoef, Senno; Pijpe, Anouk; van 't Veer, Laura; van Leeuwen, Flora; R, M. A.; C, J. M.; van den Ouweland, Ans; Kriege, Mieke; Schutte, Mieke; Hooning, Maartje; Seynaeve, Caroline; Tollenaar, Rob; van Asperen, Christi; W, J.; Vreeswijk, Maaike; Hoogerbrugge, Nicoline; L, M. J.; Ausems, Margreet; v d L, R.; A, C. M.; van Os, Theo; Meijers-Heijboer, Hanne; Gille, Hans; Gomez-Garcia, Encarna; Blok, Rien; P, S.; C, M.; O, C.; F, D.; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; C, T.; McKeown, Carole; Burgess, Lucy; Donaldson, Alan; Paterson, Joan; Murray, Alexandra; Rogers, Mark; McCann, Emma; Kennedy, John; Barton, David; Porteous, Mary; Brewer, Carole; Kivuva, Emma; Searle, Anne; Goodman, Selina; D, R.; Murday, Victoria; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; I, L.; Pichert, Gabriella; Langman, Caroline; Dorkins, Huw; Barwell, Julian; C, C.; Bishop, Tim; Miller, Julie; Ellis, Ian; E, D. G.; L, F.; Holt, Felicity; Male, Alison; Robinson, Anne; Gardiner, Carol; Douglas, Fiona; Walker, Lisa; Durell, Sarah; Eeles, Ros; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Mitra, Anita; Cook, Jackie; Quarrell, Oliver; Bardsley, Cathryn; H, S.; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Crawford, Gillian; Tyler, Emma; McBride, Donna; Lucassen, Anneke; S, O. M.; Barjhoux, Laure; Giraud, Sophie; Mazoyer, Sylvie; S-L, D.; Gauthier-Villars, Marion; Houdayer, Claude; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; B-d-P, B.; R, A.; Byrde, Veronque; Capoulade, Corinne; L, G. M.; Bignon, Yves-Jean; Uhrhammer, Nancy; Lasset, Christine; Bonadona, Valeri; Hardouin, Agnes; Berthet, Pascaline; Sobol, Hagay; Bourdon, Violaine; Eisinger, Francos; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Coupier, Isabelle; Peyrat, Jean-Philippe; Fournier, Joelle; Vennin, Philippe; Adenis, Claude; Rouleau, Etienne; Lidereau, Rosette; Demange, Liliane; Nogues, Catherine; Muller, Daniel; Fricker, Jean-Pierre; L, M.; S, N.; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Leroux, Dominique; Dreyfus, Helene; Rebischung, Christine; Olivier-Faivre, Laurence; P, F.; Frena, Marc; Lynch, Henry T.; G, A. K.; S, R. K.; S, J.; Durocher, Francine; Laframboise, Rachel; Plante, Marie; Bridge, Peter; Parboosingh, Jilian; Chiquette, Jocelyne; Lesperance, Bernard; S, C. I.; F, L.; Eva, Machakova; Miroslava, Lukesova; de Paepe, Anne; Poppe, Bruce; K, P.; Nordling, Margareta; Bergman, Annika; Einbeigi, Zakaria; Stenmark-Askmalm, Marie; Liedgren, Sigrun; Borg, Ake; Loman, Niklas; Olsson, Hakan; Kristoffersson, Ulf; Jernstrom, Helena; H, K.; Henrisson, Karin; Lindblom, Annika; Arver, Brita; von Wachenfeldt, Anna; Liljegren, Annelie; B-B, G.; R, J.; A, A.

    2009-01-01

    Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and

  10. Randomized trial of pragmatic education for low-risk COPD patients: impact on hospitalizations and emergency department visits.

    Science.gov (United States)

    Siddique, Haamid H; Olson, Raymond H; Parenti, Connie M; Rector, Thomas S; Caldwell, Michael; Dewan, Naresh A; Rice, Kathryn L

    2012-01-01

    Most interventions aimed at reducing hospitalizations and emergency department (ED) visits in patients with chronic obstructive pulmonary disease (COPD) have employed resource-intense programs in high-risk individuals. Although COPD is a progressive disease, little is known about the effectiveness of proactive interventions aimed at preventing hospitalizations and ED visits in the much larger population of low-risk (no known COPD-related hospitalizations or ED visits in the prior year) patients, some of whom will eventually become high-risk. We tested the effect of a simple educational and self-efficacy intervention (n = 2243) versus usual care (n = 2182) on COPD/breathing-related ED visits and hospitalizations in a randomized study of low-risk patients at three Veterans Affairs (VA) medical centers in the upper Midwest. Administrative data was used to track VA admissions and ED visits. A patient survey was used to determine health-related events outside the VA. Rates of COPD-related VA hospitalizations in the education and usual care group were not significantly different (3.4 versus 3.6 admissions per 100 person-years, respectively; 95% CI of difference -1.3 to 1.0, P = 0.77). The much higher patient-reported rates of non-VA hospitalizations for breathing-related problems were lower in the education group (14.0 versus 19.0 per 100 person-years; 95% CI -8.6 to -1.4, P = 0.006). Rates of COPD-related VA ED visits were not significantly different (6.8 versus 5.3; 95% CI -0.1 to 3.0, P = 0.07), nor were non-VA ED visits (32.4 versus 36.5; 95% CI -9.3 to 1.1, P = 0.12). All-cause VA admission and ED rates did not differ. Mortality rates (6.9 versus 8.3 per 100 person-years, respectively; 95% CI -3.0 to 0.4, P = 0.13) did not differ. An educational intervention that is practical for large numbers of low-risk patients with COPD may reduce the rate of breathing-related hospitalizations. Further research that more closely tracks hospitalizations to non-VA facilities is

  11. Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer

    Science.gov (United States)

    Dignam, James J.; Amin, Mahul B.; Bruner, Deborah W.; Low, Daniel; Swanson, Gregory P.; Shah, Amit B.; D’Souza, David P.; Michalski, Jeff M.; Dayes, Ian S.; Seaward, Samantha A.; Hall, William A.; Nguyen, Paul L.; Pisansky, Thomas M.; Faria, Sergio L.; Chen, Yuhchyau; Koontz, Bridget F.; Paulus, Rebecca; Sandler, Howard M.

    2016-01-01

    Purpose Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation—fewer treatments but at a higher dose per treatment—may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. Patients and Methods A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). Results A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. Conclusion In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT. PMID:27044935

  12. Attitudes toward anticoagulant treatment among nonvalvular atrial fibrillation patients at high risk of stroke and low risk of bleed

    Directory of Open Access Journals (Sweden)

    Crivera C

    2016-05-01

    Full Text Available Concetta Crivera,1 Winnie W Nelson,1 Jeff R Schein,1 Edward A Witt2 1Janssen Scientific Affairs, LLC, Raritan, 2Kantar Health, Princeton, NJ, USA Background: Atrial fibrillation (AF is associated with an increased risk of stroke. Anticoagulant (AC therapies are effective at treating AF, but carry with them an increased risk of bleed. Research suggests that a large proportion of AF patients who have high risk of stroke and low risk of bleeding are not currently receiving AC treatment. The goal of this study was to understand the reasons why these patients do not engage in this potentially life-saving treatment.Method: Through a self-report online survey, using validated instruments, 1,184 US adults who self-reported a diagnosis of AF were screened for the risk of stroke and bleed. Of these patients, 230 (19.4% were at high risk of stroke, low risk of bleed, and not currently using an AC treatment, and were asked follow-up questions to assess their reasons for nontreatment, attitudes toward treatment, and attitudes toward dosing regimens.Results: The most common reasons patients stopped AC treatment were concerns regarding bleeding (27.8% and other medical concerns (26.6%, whereas the most common reason cited for not being prescribed an AC in the first place was the use of antiplatelet therapy as an alternative (57.1%. In both cases, potentially erroneous decisions regarding perceived stoke and/or bleeding risk were also a factor. Finally, the largest factors regarding attitudes toward treatment and dosing regimen were instructions from an authority figure (eg, physician, pharmacist and ease of use, respectively.Conclusion: Results suggest that many AF patients who are at high risk of stroke but at low risk of bleed may not be receiving AC due to potentially inaccurate beliefs about risk. This study also found that AF patients place trust in physicians above other factors such as cost when making treatment decisions. Increased education of

  13. Shift-Variant Multidimensional Systems.

    Science.gov (United States)

    1985-05-29

    x,y;u,v) is the system response at (x,y) to an unit impulse applied at (u,v). The presence of additive noise in the preceding input-output model of a...space model developed works very effi- ciently to deblur images affected by 2-D linear shift- varying blurs, its use, in presence of noise needs to be...causal linear shift-variant (LSV) system, whose impulse res- ponse is a K-th order degenerate sequence, a K-th order state-space model was obtained

  14. Genetic variants at chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 influence the risk of breast cancer in men.

    Directory of Open Access Journals (Sweden)

    Nick Orr

    2011-09-01

    Full Text Available Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS have recently identified common single nucleotide polymorphisms (SNPs that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35 (odds ratio (OR  = 1.30, p = 7.98×10⁻⁴, rs10941679 (5p12 (OR = 1.26, p = 0.007, rs9383938 (6q25.1 (OR = 1.39, p = 0.004, rs2981579 (FGFR2 (OR = 1.18, p = 0.03, and rs3803662 (TOX3 (OR = 1.48, p = 4.04×10⁻⁶. Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs--rs13387042 (2q35, rs3803662 (TOX3, and rs6504950 (COX11--showed significant differences in ORs (p<0.05 between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development.

  15. Isolated port-site metastasis after surgical staging for low-risk endometrioid endometrial cancer: A case report.

    Science.gov (United States)

    Mautone, Daniele; Dall'asta, Andrea; Monica, Michela; Galli, Letizia; Capozzi, Vito Andrea; Marchesi, Federico; Giordano, Giovanna; Berretta, Roberto

    2016-07-01

    Port-site metastases (PSMs) are well-known potential complications of laparoscopic surgery for gynaecologic malignancies. The present case study reports PSM following laparoscopic surgery for Stage IA Grade 1 endometrioid endometrial cancer (EEC). The recurrence developed within 7 months following primary surgery and required surgical excision followed by adjuvant chemo-radio therapy. After 9 months, the patient remains disease-free. PSMs are rare complications following laparoscopic surgery. Amongst the 23 cases of endometrial cancer PSMs reported so far, only 4 followed EEC Stage IA Grade 1-2. The present study reports a rare case of PSM after Stage IA Grade 1 EEC. The clinical and prognostic relevance of PSMs has not been identified so far; and it is not known whether PSMs represent a local recurrence or a systemic recurrence. Surgeons should be aware that even low-risk EEC may be followed by PSMs and should take steps to prevent these rare recurrences.

  16. Severe adverse maternal outcomes among low risk women with planned home versus hospital births in the Netherlands: nationwide cohort study.

    Science.gov (United States)

    de Jonge, Ank; Mesman, Jeanette A J M; Manniën, Judith; Zwart, Joost J; van Dillen, Jeroen; van Roosmalen, Jos

    2013-06-13

    To test the hypothesis that low risk women at the onset of labour with planned home birth have a higher rate of severe acute maternal morbidity than women with planned hospital birth, and to compare the rate of postpartum haemorrhage and manual removal of placenta. Cohort study using a linked dataset. Information on all cases of severe acute maternal morbidity in the Netherlands collected by the national study into ethnic determinants of maternal morbidity in the netherlands (LEMMoN study), 1 August 2004 to 1 August 2006, merged with data from the Netherlands perinatal register of all births occurring during the same period. 146 752 low risk women in primary care at the onset of labour. Severe acute maternal morbidity (admission to an intensive care unit, eclampsia, blood transfusion of four or more packed cells, and other serious events), postpartum haemorrhage, and manual removal of placenta. Overall, 92 333 (62.9%) women had a planned home birth and 54 419 (37.1%) a planned hospital birth. The rate of severe acute maternal morbidity among planned primary care births was 2.0 per 1000 births. For nulliparous women the rate for planned home versus planned hospital birth was 2.3 versus 3.1 per 1000 births (adjusted odds ratio 0.77, 95% confidence interval 0.56 to 1.06), relative risk reduction 25.7% (95% confidence interval -0.1% to 53.5%), the rate of postpartum haemorrhage was 43.1 versus 43.3 (0.92, 0.85 to 1.00 and 0.5%, -6.8% to 7.9%), and the rate of manual removal of placenta was 29.0 versus 29.8 (0.91, 0.83 to 1.00 and 2.8%, -6.1% to 11.8%). For parous women the rate of severe acute maternal morbidity for planned home versus planned hospital birth was 1.0 versus 2.3 per 1000 births (0.43, 0.29 to 0.63 and 58.3%, 33.2% to 87.5%), the rate of postpartum haemorrhage was 19.6 versus 37.6 (0.50, 0.46 to 0.55 and 47.9%, 41.2% to 54.7%), and the rate of manual removal of placenta was 8.5 versus 19.6 (0.41, 0.36 to 0.47 and 56.9%, 47.9% to 66.3%). Low risk

  17. The Effect of Parenting Style on Social Smiling in Infants at High and Low Risk for ASD.

    Science.gov (United States)

    Harker, Colleen M; Ibañez, Lisa V; Nguyen, Thanh P; Messinger, Daniel S; Stone, Wendy L

    2016-07-01

    This study examined how parenting style at 9 months predicts growth in infant social engagement (i.e., social smiling) between 9 and 18 months during a free-play interaction in infants at high (HR-infants) and low (LR-infants) familial risk for autism spectrum disorder (ASD). Results indicated that across all infants, higher levels of maternal responsiveness were concurrently associated with higher levels of social smiling, while higher levels of maternal directiveness predicted slower growth in social smiling. When accounting for maternal directiveness, which was higher in mothers of HR-infants, HR-infants exhibited greater growth in social smiling than LR-infants. Overall, each parenting style appears to make a unique contribution to the development of social engagement in infants at high- and low-risk for ASD.

  18. Differences in Neural Correlates of Speech Perception in 3 Month Olds at High and Low Risk for Autism Spectrum Disorder.

    Science.gov (United States)

    Edwards, Laura A; Wagner, Jennifer B; Tager-Flusberg, Helen; Nelson, Charles A

    2017-10-01

    In this study, we investigated neural precursors of language acquisition as potential endophenotypes of autism spectrum disorder (ASD) in 3-month-old infants at high and low familial ASD risk. Infants were imaged using functional near-infrared spectroscopy while they listened to auditory stimuli containing syllable repetitions; their neural responses were analyzed over left and right temporal regions. While female low risk infants showed initial neural activation that decreased over exposure to repetition-based stimuli, potentially indicating a habituation response to repetition in speech, female high risk infants showed no changes in neural activity over exposure. This finding may indicate a potential neural endophenotype of language development or ASD specific to females at risk for the disorder.

  19. Identifying emergency department patients with chest pain who are at low risk for acute coronary syndromes [digest].

    Science.gov (United States)

    Markel, David; Kim, Jeremy

    2017-07-21

    Though a minority of patients presenting to the emergency department with chest pain have acute coronary syndromes,identifying the patients who may be safely discharged and determining whether further testing is needed remains challenging. From the prehospital care setting to disposition and follow-up, this systematic review addresses the fundamentals of the emergency department evaluation of patients determined to be at low risk for acute coronary syndromes or adverse outcomes. Clinical risk scores are discussed, as well as the evidence and indications for confirmatory testing. The emerging role of new technologies, such as high-sensitivity troponin assays and advanced imaging techniques, are also presented. [Points & Pearls is a digest of Emergency Medicine Practice].

  20. Outcomes of Low-Risk Ductal Carcinoma In Situ in Southeast Asian Women Treated With Breast Conservation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Fuh Yong, E-mail: fuhyong@yahoo.com [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); Wang, Fuqiang [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); Chen, John Ju [Department of Cancer Informatics, National Cancer Centre Singapore (Singapore); Tan, Chiew Har [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); Tan, Puay Hoon [Department of Pathology, Singapore General Hospital (Singapore)

    2014-04-01

    Purpose: To examine the outcomes of Southeast Asian (SEA) women with low-risk ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and adjuvant radiation therapy. Methods and Materials: Retrospective chart reviews of patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were included. Most patients received adjuvant radiation therapy (RT) consisting of whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed. Results: Of 744 patients with pathologic diagnosis of pure DCIS identified, 273 met the selection criteria: low-intermediate grade (LIG), n=219; high grade (HG), n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%, respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not. There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT. The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5 years, giving an estimated IBTR rate of 4.5% at 10 years. Conclusions: SEA women with screen-detected DCIS have exceedingly low rates of IBTR after BCS, comparable to that observed in reports of similar patients with low-risk DCIS treated with adjuvant radiation.

  1. Outcomes of Low-Risk Ductal Carcinoma In Situ in Southeast Asian Women Treated With Breast Conservation Therapy

    International Nuclear Information System (INIS)

    Wong, Fuh Yong; Wang, Fuqiang; Chen, John Ju; Tan, Chiew Har; Tan, Puay Hoon

    2014-01-01

    Purpose: To examine the outcomes of Southeast Asian (SEA) women with low-risk ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and adjuvant radiation therapy. Methods and Materials: Retrospective chart reviews of patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were included. Most patients received adjuvant radiation therapy (RT) consisting of whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed. Results: Of 744 patients with pathologic diagnosis of pure DCIS identified, 273 met the selection criteria: low-intermediate grade (LIG), n=219; high grade (HG), n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%, respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not. There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT. The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5 years, giving an estimated IBTR rate of 4.5% at 10 years. Conclusions: SEA women with screen-detected DCIS have exceedingly low rates of IBTR after BCS, comparable to that observed in reports of similar patients with low-risk DCIS treated with adjuvant radiation

  2. Factors contributing to postpartum blood-loss in low-risk mothers through expectant management in Japanese birth centres.

    Science.gov (United States)

    Eto, Hiromi; Hasegawa, Ayako; Kataoka, Yaeko; Porter, Sarah E

    2017-08-01

    To describe aspects of expectant midwifery care for low-risk women conducted in midwifery-managed birth centres during the first two critical hours after delivery and to compare differences between midwifery care, client factors and postpartum blood loss volume. As a secondary analysis from a larger study, this descriptive retrospective study examined data from birth records of 4051 women who birthed from 2001 to 2006 at nine (21%) of the 43 midwifery centres in Tokyo. Nonparametric and parametric analyses identified factors related to increased blood loss. Interviews to establish sequence of midwifery care were conducted. The midwifery centres provided care based on expectant management principles from birth to after expulsion of the placenta. Approximately 63.3% of women were within the normal limits of blood loss volume under 500g. A minority of women (12.9%) experienced blood loss between 500 and 800g and 4% had blood loss exceeding 1000g. Blood loss volume tended to increase with infant birth weight and duration of delivery. The total blood loss volume was significantly higher for primiparas than for multiparas during the critical two hours after delivery and for immediately after delivery, yet blood loss volume was significantly higher for multiparas than for primiparas during the first hour after delivery. Preventive uterine massage and umbilical cord clamping after placenta expulsion resulted in statistically significant less blood loss. Identified were two patterns of midwifery care based on expectant management principles from birth to after expulsion of the placenta. The practice of expectant management was not a significant factor for increased postpartum blood loss. These results detail specific midwifery practices and highlight the clinical significance of expectant management with low risk pregnant women experiencing a normal delivery. Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  3. Less-Restrictive Food Intake During Labor in Low-Risk Singleton Pregnancies: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Ciardulli, Andrea; Saccone, Gabriele; Anastasio, Hannah; Berghella, Vincenzo

    2017-03-01

    To evaluate benefits and harms of food intake during labor. Electronic databases such as MEDLINE and ClinicalTrials.gov were searched from their inception until October 2016. We included randomized trials comparing a policy of less-restrictive food intake with a policy of more restrictive food intake during labor. The primary outcome was the mean duration of labor. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of either a relative risk or a mean difference with 95% confidence interval (CI). Ten trials, including 3,982 laboring women, were included. All the studies involved laboring singletons considered at low risk because they had no obstetric or medical complications that would increase the likelihood of cesarean delivery. In three studies, women were allowed to select from a low-residue diet throughout the course of labor. One study had honey date syrup as the allowed food intake. Five studies had carbohydrate drinks as food intake in labor. The last one was the only trial that allowed unrestrictive food intake. In the included studies, all women in the intervention group were allowed the assigned food intake until delivery, whereas women in a control group were allowed only ice chips, water, or sips of water until delivery. A policy of less-restrictive food intake was associated with a significantly shorter duration of labor (mean difference -16 minutes, 95% CI -25 to -7). No other benefits or harms in obstetric or neonatal outcome were noticed. Regurgitation during general anesthesia and Mendelson syndrome did not occur in either group. Women with low-risk singleton pregnancies who were allowed to eat more freely during labor had a shorter duration of labor. A policy of less-restrictive food intake during labor did not influence other obstetric or neonatal outcomes nor did it increase the incidence of vomiting. Operative delivery rates were similar.

  4. The value of routine mid-trimester ultrasound in low-risk pregnancies at primary care level

    Directory of Open Access Journals (Sweden)

    B van Dyk

    2008-12-01

    Full Text Available This study investigated the effect of routine second-trimester ultrasound scanning on obstetric management and pregnancy outcomes. This was an open cluster, randomised, controlled trial. Clusters of women with low-risk pregnancies presenting in the second trimester were randomised to receive an ultrasound scan followed by usual antenatal care, or to an unscanned control group undergoing conventional antenatal care only. Out of the 962 women randomised, follow-up was successful for 804 (83.6%, with 416 allocated to the ultrasound scan group and 388 controls. There were no significant differences between the ultrasound scan group and the control group in terms of prenatal hospitalisation, mode of delivery, miscarriage, perinatal mortality rate and low birthweight rate. Ultrasound dating was associated with a lower rate of induction of labour for post-term pregnancy (1.4% vs. 3.6%; P=0.049. However, ultrasound scanning in low-risk pregnancies was not associated with improvements in pregnancy outcome. Opsomming Hierdie studie het die effek van roetine mid-trimester ultraklankskandering op swangerskapsorg en –uitkomste ondersoek. Dit was ’n oop tros, lukrake, beheerde proef. Groepe vroue met laerisikoswanger- skap in die midtrimester is lukraak toegewys vir ’n ultraklank-skandering, gevolg deur voorgeskrewe voorgeboor-tesorg, of vir ’n kontrolegroep wat voorgeboortesorg volgens nasionaal voorgeskrewe protokol sonder skandering ontvang het. Van die 962 vroue wat aan die steekproef deelgeneem het kon data vir 804 (83.6% suksesvol opgevolg word, met 416 in die ultraklankgroep en 388 in die kontrolegroep. Geen beduidende verskille is tussen die twee groepe gevind ten opsigte van voorgeboorte-hospitalisasie, geboortemetode, miskraamstatistiek, perinatale komplikasies of laegeboortegewig nie. Ultraklankdatering van swangerskappe is met minder kraaminduksie (1.4% teen 3.6%; P=0.049 vir natrimesterswangerskap geassosieer. Roetine ultraklankskandering

  5. Omission of Breast Radiotherapy in Low-risk Luminal A Breast Cancer: Impact on Health Care Costs.

    Science.gov (United States)

    Han, K; Yap, M L; Yong, J H E; Mittmann, N; Hoch, J S; Fyles, A W; Warde, P; Gutierrez, E; Lymberiou, T; Foxcroft, S; Liu, F F

    2016-09-01

    The economic burden of cancer care is substantial, including steep increases in costs for breast cancer management. There is mounting evidence that women age ≥ 60 years with grade I/II T1N0 luminal A (ER/PR+, HER2- and Ki67 ≤ 13%) breast cancer have such low local recurrence rates that adjuvant breast radiotherapy might offer limited value. We aimed to determine the total savings to a publicly funded health care system should omission of radiotherapy become standard of care for these patients. The number of women aged ≥ 60 years who received adjuvant radiotherapy for T1N0 ER+ HER2- breast cancer in Ontario was obtained from the provincial cancer agency. The cost of adjuvant breast radiotherapy was estimated through activity-based costing from a public payer perspective. The total saving was calculated by multiplying the estimated number of luminal A cases that received radiotherapy by the cost of radiotherapy minus Ki-67 testing. In 2010, 748 women age ≥ 60 years underwent surgery for pT1N0 ER+ HER2- breast cancer; 539 (72%) underwent adjuvant radiotherapy, of whom 329 were estimated to be grade I/II luminal A subtype. The cost of adjuvant breast radiotherapy per case was estimated at $6135.85; the cost of Ki-67 at $114.71. This translated into an annual saving of about $2.0million if radiotherapy was omitted for all low-risk luminal A breast cancer patients in Ontario and $5.1million across Canada. There will be significant savings to the health care system should omission of radiotherapy become standard practice for women with low-risk luminal A breast cancer. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  6. Outcomes of peptic ulcer bleeding following treatment with proton pump inhibitors in routine clinical practice: 935 patients with high- or low-risk stigmata.

    Science.gov (United States)

    Lanas, Angel; Carrera-Lasfuentes, Patricia; García-Rodríguez, Luis A; García, Santiago; Arroyo-Villarino, María Teresa; Ponce, Julio; Bujanda, Luis; Calleja, José L; Polo-Tomas, Mónica; Calvet, Xavier; Feu, Faust; Perez-Aisa, Angeles

    2014-10-01

    To assess rates of further bleeding, surgery and mortality in patients hospitalized owing to peptic ulcer bleeding. Consecutive patients hospitalized for peptic ulcer bleeding and treated with a proton pump inhibitor (PPI) (esomeprazole or pantoprazole) were identified retrospectively in 12 centers in Spain. Patients were included if they had high-risk stigmata (Forrest class Ia-IIb, underwent therapeutic endoscopy and received intravenous PPI ≥120 mg/day for ≥24 h) or low-risk stigmata (Forrest class IIc-III, underwent no therapeutic endoscopy and received intravenous or oral PPI [any dose]). Of 935 identified patients, 58.3% had high-risk stigmata and 41.7% had low-risk stigmata. After endoscopy, 88.3% of high-risk patients and 22.1% of low-risk patients received intravenous PPI therapy at doses of at least 160 mg/day. Further bleeding within 72 h occurred in 9.4% and 2.1% of high- and low-risk patients, respectively (p peptic ulcer bleeding and treated with PPIs, patients with high-risk stigmata have a higher risk of further bleeding and surgery, but not of death, than those with low-risk stigmata.

  7. Different pituitary. beta. -endorphin and adrenal cortisol response to ethanol in individuals with high and low risk for future development of alcoholism

    Energy Technology Data Exchange (ETDEWEB)

    Gianoulakis, C.G.; Beliveau, D.; Angelogianni, P.; Meaney, M.; Thavundayil, J.; Tawar, V.; Dumas, M. (McGill Univ., Quebec (Canada))

    1989-01-01

    The purpose of the present studies was to investigate the activity of the adrenal gland and the pituitary {beta}-endorphin system in individuals from families with a 3 generation history of alcoholism, High Risk group, or from families without history of alcoholism, Low Risk group. On the day of testing, blood sample was taken at 9:00 a.m., then the subject drank a placebo drink or an ethanol solution. Additional blood samples were taken at 15, 45 and 120 minutes post-drink. Results indicated that individuals of the High Risk group had lower basal levels of {beta}-endorphin like immunoreactivity ({beta}-EPLIR) than individuals of the Low Risk group. The dose of 0.5 g ethanol/kg B.Wt. induced an induce an increase in the plasma content of {beta}-EPLIR of the High Risk group, but not of the Low Risk group. In the Low Risk group ethanol did not induce an increase above the 9:00 a.m. levels, however, it attenuated the {beta}-endorphin decrease overtime, observed following the placebo drink. Analysis of {beta}-endorphin-like peptides in the plasma of the High Risk group, with Sephadex G-75 chromatography indicated that the major component of the plasma {beta}-EPLIR was {beta}-lipotropin. Plasma cortisol levels, following ethanol intake, presented a small increase in the High Risk group but not in the Low Risk group.

  8. Monotherapy of aspirin or warfarin for prevention of ischemic stroke in low-risk atrial fibrillation: A Easter Asian population-based study.

    Science.gov (United States)

    Liu, Chieh-Yu; Chen, Hui-Chun

    2018-05-02

    This study aimed to investigate the effectiveness of monotherapy aspirin and warfarin for stroke prevention in low-risk atrial fibrillation (AF) by using a population-based cohort study in Taiwan. A newly diagnosed low-risk AF patient cohort were identified by using National Health Insurance Research Database (NHIRD) in Taiwan in 2008. The study cohort was observed with a follow-up of 2 years to examine the onset of ischemic stroke (IS) (to 2010). The longitudinal data were analyzed by using generalized estimation equations (GEE). A total of 8,065 newly-diagnosed low-risk AF patients were identified in 2008. 7.4% were prescribed with aspirin and 4.6% were prescribed with warfarin. The GEE results showed that low-risk AF patients with hypertension who received warfarin were associated with a statistically significant 58.4% reduction of IS risk (OR = 0.416, p = 0.024, 95% CI 0.194-0.891). Additionally, low-risk AF patients with hyperlipidemia who received warfarin were associated with a 69.3% reduction of IS risk (OR = 0.307, p = 0.044, 95% CI 0.097-0.969). Warfarin is suggested to be prescribed in preventing ischemic stroke for low-stroke-risk atrial fibrillation patients with hypertension and hyperlipidemia.

  9. Effects of caesarean section on maternal health in low risk nulliparous women: a prospective matched cohort study in Shanghai, China

    Directory of Open Access Journals (Sweden)

    Gao Xiao-ling

    2010-12-01

    Full Text Available Abstract Background Rates of caesarean section are progressively increasing in many parts of the world. As a result of psychosocial factors there has been an increasing tendency for pregnant women without justifiable medical indications for caesarean section to ask for this procedure in China. A critical examination of this issue in relation to maternal outcomes is important. At present there are no clinical trials to help assess the risks and benefits of caesarean section in low risk women. To fill the gap left by trials, this indication-matched cohort study was carried out to examine prospectively the outcomes of caesarean section on women with no absolute obstetric indication compared with similar women who had vaginal delivery. Methods An indication-matched cohort study was undertaken to compare maternal outcomes following caesarean section with those undergoing vaginal delivery, in which the two groups were matched for non-absolute indications. 301 nulliparous women with caesarean section were matched successfully with 301 women who delivered vaginally in the Maternal and Children's Hospitals (MCHs in Shanghai, China. Logistic regression model or binomial regression model was used to estimate the relative risk (RR directly. Adjusted RRs were calculated adjusting for propensity score and medical indications. Results The incidence of total complications was 2.2 times higher in the caesarean section group during hospitalization post-partum, compared with the vaginal delivery group (RR = 2.2; 95% CI: 1.1-4.4. The risk of haemorrhage from the start of labour until 2 hours post-partum was significantly higher in the caesarean group (RR = 5.6; 95% CI: 1.2-26.9. The risk of chronic abdominal pain was significantly higher for the caesarean section group (RR = 3.6; 95% CI: 1.2-10.9 than for the vaginal delivery group within 12 months post-partum. The two groups had similar incidences of anaemia and complicating infections such as wound complications

  10. Planned home versus planned hospital births in women at low-risk pregnancy: A systematic review with meta-analysis.

    Science.gov (United States)

    Rossi, A Cristina; Prefumo, Federico

    2018-03-01

    New interest in home birth have recently arisen in women at low risk pregnancy. Maternal and neonatal morbidity of women planning delivery at home has yet to be comprehensively quantified. We aimed to quantify pregnancy outcomes following planned home (PHB) versus planned hospital birth (PHos). We did a systematic review of maternal and neonatal morbidity following planned home (PHB) versus planned hospital birth (PHos). We included prospective, retrospective, cohort and case-control studies of low risk pregnancy outcomes according to planning place of birth, identified from January 2000 to June 2017. We excluded studies in which high-risk pregnancy and composite morbidity were included. Outcomes of interest were: maternal and neonatal morbidity/mortality, medical interventions, and delivery mode. We pooled estimates of the association between outcomes and planning place of birth using meta-analyses. The study protocol is registered with PROSPERO, protocol number CRD42017058016. We included 8 studies of the 4294 records identified, consisting in 14,637 (32.6%) in PHB and 30,177 (67.4%) in PHos group. Spontaneous delivery was significantly higher in PHB than PHos group (OR: 2.075; 95%CI:1.654-2.063) group. Women in PHB group were less likely to undergo cesarean section compared with women in PHos (OR:0.607; 95%CI:0.553-0.667) group. PHB group was less likely to receive medical interventions than PHos group. The risk of fetal dystocia was lower in PHB than PHos group (OR:0.287; 95%CI:0.133-0.618). The risk of post-partum hemorrhage was lower in PHB than PHos group (OR:0.692; 95% CI.0.634-0.755). The two groups were similar with regard to neonatal morbidity and mortality. Births assisted at hospital are more likely to receive medical interventions, fetal monitoring and prompt delivery in case of obstetrical complications. Further studies are needed in order to clarify whether home births are as safe as hospital births. Copyright © 2018 Elsevier B.V. All rights

  11. Developing consistent pronunciation models for phonemic variants

    CSIR Research Space (South Africa)

    Davel, M

    2006-09-01

    Full Text Available Pronunciation lexicons often contain pronunciation variants. This can create two problems: It can be difficult to define these variants in an internally consistent way and it can also be difficult to extract generalised grapheme-to-phoneme rule sets...

  12. Semantic prioritization of novel causative genomic variants

    KAUST Repository

    Boudellioua, Imene

    2017-04-17

    Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.

  13. Semantic prioritization of novel causative genomic variants

    KAUST Repository

    Boudellioua, Imene; Mohamad Razali, Rozaimi; Kulmanov, Maxat; Hashish, Yasmeen; Bajic, Vladimir B.; Goncalves-Serra, Eva; Schoenmakers, Nadia; Gkoutos, Georgios V.; Schofield, Paul N.; Hoehndorf, Robert

    2017-01-01

    Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.

  14. Fundamental Characteristics of Industrial Variant Specification Systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars

    2004-01-01

    fundamental concepts related to this task, which are relevant to understand for academia and practitioners working with the subject. This is done through a description of variant specification tasks and typical aspects of system solutions. To support the description of variant specification tasks and systems...

  15. Characterization of form variants of Xenorhabdus luminescens.

    NARCIS (Netherlands)

    Gerritsen, L.J.M.; Raay, de G.; Smits, P.H.

    1992-01-01

    From Xenorhabdus luminescens XE-87.3 four variants were isolated. One, which produced a red pigment and antibiotics, was luminescent, and could take up dye from culture media, was considered the primary form (XE-red). A pink-pigmented variant (XE-pink) differed from the primary form only in

  16. CLEVER: Clique-Enumerating Variant Finder

    NARCIS (Netherlands)

    Marschall, T.; Costa, I.; Canzar, S.; bauer, m; Klau, G.W.; Schliep, A.; Schönhuth, A.

    2012-01-01

    Motivation: Next-generation sequencing techniques have facilitated a large-scale analysis of human genetic variation. Despite the advances in sequencing speed, the computational discovery of structural variants is not yet standard. It is likely that many variants have remained undiscovered in most

  17. Variant Review with the Integrative Genomics Viewer.

    Science.gov (United States)

    Robinson, James T; Thorvaldsdóttir, Helga; Wenger, Aaron M; Zehir, Ahmet; Mesirov, Jill P

    2017-11-01

    Manual review of aligned reads for confirmation and interpretation of variant calls is an important step in many variant calling pipelines for next-generation sequencing (NGS) data. Visual inspection can greatly increase the confidence in calls, reduce the risk of false positives, and help characterize complex events. The Integrative Genomics Viewer (IGV) was one of the first tools to provide NGS data visualization, and it currently provides a rich set of tools for inspection, validation, and interpretation of NGS datasets, as well as other types of genomic data. Here, we present a short overview of IGV's variant review features for both single-nucleotide variants and structural variants, with examples from both cancer and germline datasets. IGV is freely available at https://www.igv.org Cancer Res; 77(21); e31-34. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Local binary patterns new variants and applications

    CERN Document Server

    Jain, Lakhmi; Nanni, Loris; Lumini, Alessandra

    2014-01-01

    This book introduces Local Binary Patterns (LBP), arguably one of the most powerful texture descriptors, and LBP variants. This volume provides the latest reviews of the literature and a presentation of some of the best LBP variants by researchers at the forefront of textual analysis research and research on LBP descriptors and variants. The value of LBP variants is illustrated with reported experiments using many databases representing a diversity of computer vision applications in medicine, biometrics, and other areas. There is also a chapter that provides an excellent theoretical foundation for texture analysis and LBP in particular. A special section focuses on LBP and LBP variants in the area of face recognition, including thermal face recognition. This book will be of value to anyone already in the field as well as to those interested in learning more about this powerful family of texture descriptors.

  19. Congenital anomalies and normal skeletal variants

    International Nuclear Information System (INIS)

    Guebert, G.M.; Yochum, T.R.; Rowe, L.J.

    1987-01-01

    Congenital anomalies and normal skeletal variants are a common occurrence in clinical practice. In this chapter a large number of skeletal anomalies of the spine and pelvis are reviewed. Some of the more common skeletal anomalies of the extremities are also presented. The second section of this chapter deals with normal skeletal variants. Some of these variants may simulate certain disease processes. In some instances there are no clear-cut distinctions between skeletal variants and anomalies; therefore, there may be some overlap of material. The congenital anomalies are presented initially with accompanying text, photos, and references, beginning with the skull and proceeding caudally through the spine to then include the pelvis and extremities. The normal skeletal variants section is presented in an anatomical atlas format without text or references

  20. Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study.

    Science.gov (United States)

    Kazemier, Brenda M; Schneeberger, Caroline; De Miranda, Esteriek; Van Wassenaer, Aleid; Bossuyt, Patrick M; Vogelvang, Tatjana E; Reijnders, Frans J L; Delemarre, Friso M C; Verhoeven, Corine J M; Oudijk, Martijn A; Van Der Ven, Jeanine A; Kuiper, Petra N; Feiertag, Nicolette; Ott, Alewijn; De Groot, Christianne J M; Mol, Ben Willem J; Geerlings, Suzanne E

    2012-06-21

    The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality. We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥105 colony forming units (CFU)/mL of a single microorganism or two different colonies but one ≥105 CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind). Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs. This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16-22 weeks of pregnancy and subsequent nitrofurantoin treatment. Dutch trial registry: NTR-3068.

  1. Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study

    Directory of Open Access Journals (Sweden)

    Kazemier Brenda M

    2012-06-01

    Full Text Available Abstract Background The prevalence of asymptomatic bacteriuria (ASB in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality. Methods/Design We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥105 colony forming units (CFU/mL of a single microorganism or two different colonies but one ≥105 CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind. Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs. Discussion This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16–22 weeks of pregnancy and subsequent nitrofurantoin treatment. Trial registration Dutch trial registry: NTR-3068

  2. The effects of a "low-risk" diet on cell proliferation and enzymatic parameters of preneoplastic rat colon.

    Science.gov (United States)

    Goettler, D; Rao, A V; Bird, R P

    1987-01-01

    The relationship between various dietary constituents and colon cancer has been demonstrated by previous research. This study was conducted to investigate the combined effects of several dietary constituents on the preneoplastic stage of azoxymethane (AOM)-induced colon cancer in rats. A nutritionally adequate, "low-risk" (LR) diet was formulated through the modulation of dietary fat, fiber, protein, vitamins A and E, and selenium. Female F344 rats were given three weekly subcutaneous injections of AOM and were maintained on either the LR diet or a "high-risk" (HR) diet. After 12 weeks, the rats were killed and the following parameters were determined: pH of colon contents, fecal beta-glucuronidase activity, tissue ornithine decarboxylase (ODC) activity, and colonic labeling index. The pH of the colon contents and incremental labeling index were lower in the group given the LR diet and treated with AOM compared with the group given the HR diet and treated with AOM; however, no statistically significant dietary effects were observed for beta-glucuronidase and ODC activities. The results of this study indicated that the colons of rats fed the LR diet exhibited different proliferative characteristics than did the colons of rats fed the HR diet.

  3. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-28

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  4. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  5. Psychological Distress in Healthy Low-Risk First-Time Mothers during the Postpartum Period: An Exploratory Study

    Directory of Open Access Journals (Sweden)

    Christina Murphey

    2017-01-01

    Full Text Available Psychological distress, defined as depression, anxiety, and insomnia in this study, can occur following the birth of a baby as new mothers, in addition to marked physiological changes, are faced with adapting to new roles and responsibilities. We investigated the cooccurrence of stress, depression, anxiety, and insomnia in mothers during the postpartum period; tested the feasibility of study methods and procedures for use in this population; and identified new mothers interest in using cranial electrotherapy stimulation (CES as an intervention for reducing psychological distress. We recruited healthy, low-risk, English speaking first-time mothers, ages 18–32 years, with healthy babies (N=33, within 12 months of an uncomplicated birth. Participants completed the PSS, HAM-D14, HAM-A17, and PSQI19. No problems were encountered with study procedures. Mothers reported a high interest (4.9 in the potential use of CES to treat or prevent the occurrence of psychological distress. All participants (N=33 reported moderate levels of depression and anxiety, while 75.8% (n=25 reported insomnia. PSS scores were within the norms for healthy women. Further research is recommended to investigate if our findings can be replicated or if different patterns of associations emerge. Implications for clinical practice are addressed.

  6. Trichomonas vaginalis infection in a low-risk women attended in Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre

    Institute of Scientific and Technical Information of China (English)

    Norhayati Moktar; Nor Liyana Ismail; Phoy Cheng Chun; Mohamad Asyrab Sapie; Nor Farahin Abdul Kahar; Yusof Suboh; Noraina Abdul Rahim; Nor Azlin Mohamed Ismail; Tengku Shahrul Anuar

    2016-01-01

    Objective: To investigate the presence of trichomoniasis among women attending the Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre.Methods: A total of 139 high vaginal swabs were taken from the subjects and sent to the laboratory in Amies gel transport media. The specimens were examined for the presence of Trichomonas vaginalis using wet mount, Giemsa staining and cultured in Diamond’s medium. Sociodemographic characteristics and gynaecological complaints were obtained in private using structured questionnaire applied by one investigator.Results: The median age was 32 years, with an interquartile interval of 9.96. Most of the subjects were Malays(76.9%) and the remaining were Chinese(15.1%), Indians(2.2%)and other ethnic groups(5.8%). One hundred and thirty eight(99.3%) of the women were married and 98.6% had less than 6 children. More than half(75.5%) of the women’s last child birth was less than 6 years ago. Forty seven percent of them were involved in supporting administrative work and 64.7% of the women gave a history of previous or current vaginal discharge.Conclusions: The present study reported zero incidence rate of trichomoniasis. The low incidence rate was postulated due to all women who participated in this study were categorized into a low-risk group.

  7. Trichomonas vaginalis infection in a low-risk women attended in Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre

    Institute of Scientific and Technical Information of China (English)

    Norhayati Moktar; Nor Liyana Ismail; Phoy Cheng Chun; Mohamad Asyrab Sapie; Nor Farahin Abdul Kahar; Yusof Suboh; Noraina Abdul Rahim; Nor Azlin Mohamed Ismail; Tengku Shahrul Anuar

    2016-01-01

    Objective: To investigate the presence of trichomoniasis among women attending the Obstetrics and Gynaecology Clinic, Universiti Kebangsaan Malaysia Medical Centre. Methods: A total of 139 high vaginal swabs were taken from the subjects and sent to the laboratory in Amies gel transport media. The specimens were examined for the presence of Trichomonas vaginalis using wet mount, Giemsa staining and cultured in Diamond's medium. Sociodemographic characteristics and gynaecological complaints were obtained in private using structured questionnaire applied by one investigator. Results: The median age was 32 years, with an interquartile interval of 9.96. Most of the subjects were Malays (76.9%) and the remaining were Chinese (15.1%), Indians (2.2%) and other ethnic groups (5.8%). One hundred and thirty eight (99.3%) of the women were married and 98.6%had less than 6 children. More than half (75.5%) of the women's last child birth was less than 6 years ago. Forty seven percent of them were involved in supporting administrative work and 64.7% of the women gave a history of previous or current vaginal discharge. Conclusions: The present study reported zero incidence rate of trichomoniasis. The low incidence rate was postulated due to all women who participated in this study were categorized into a low-risk group.

  8. Accuracy of simple urine tests for diagnosis of urinary tract infections in low-risk pregnant women.

    Science.gov (United States)

    Feitosa, Danielle Cristina Alves; da Silva, Márcia Guimarães; de Lima Parada, Cristina Maria Garcia

    2009-01-01

    Anatomic and physiological alterations during pregnancy predispose pregnant women to urinary tract infections (UTI). This study aimed to identify the accuracy of the simple urine test for UTI diagnosis in low-risk pregnant women. Diagnostic test performance was conducted in Botucatu, SP, involving 230 pregnant women, between 2006 and 2008. Results showed 10% UTI prevalence. Sensitivity, specificity and accuracy of the simple urine test were 95.6%, 63.3% and 66.5%, respectively, in relation to UTI diagnoses. The analysis of positive (PPV) and negative (NPV) predictive values showed that, when a regular simple urine test was performed, the chance of UTI occurrence was small (NPV 99.2%). In view of an altered result for such a test, the possibility of UTI existence was small (PPV 22.4%). It was concluded that the accuracy of the simple urine test as a diagnostic means for UTI was low, and that performing a urine culture is essential for appropriate diagnosis.

  9. Morbidity in early adulthood among low-risk very low birth weight children in Turkey: a preliminary study.

    Science.gov (United States)

    Can, Gülay; Bilgin, Leyla; Tatli, Burak; Saydam, Reyhan; Coban, Asuman; Ince, Zeynep

    2012-01-01

    The objective of this study was to assess low-risk very low birth weight (VLBW) children, before the era of modern neonatal intensive care in Turkey, during adolescence. Forty-one VLBW adolescents were compared with 40 adolescents who had normal birth weight. The physical and neuromotor development, educational achievement and psychosocial status were assessed at a mean age of 17 +/- 1.6 years. VLBW adolescents were shorter than normal birth weight adolescents (p = 0.01). A major neurological abnormality (cerebral palsy) was seen in 12% and a minor neurological abnormality (tremor, coordination, behavioral and speech disorders) in 17%. VLBW adolescents had higher rates of visual problems (56% vs. 5%). School failure was present in 27%. There were no differences in behavioral problems or quality of life between the two groups, but VLBW adolescents did have a lower self-esteem score. Neurodevelopment and growth sequelae were a significant problem in VLBW adolescents. As early intervention might help to prevent or ameliorate potential problems, long-term follow-up is essential.

  10. Poster - 47: A parametrized prediction model of rectal toxicity in focal SBRT of low risk prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, Todd; Bauman, Glenn [Saint John Regional Hospital, London Regional Cancer Program (Canada)

    2016-08-15

    There has been a recent trend towards watchful waiting in place of intervention for early stage prostate cancer (CaP). However, this approach can allow for disease progression, and subsequent whole-gland therapies such as prostatectomy and whole gland irradiation can result in functional deficits or rectal toxicities or both. A controversial alternative approach for this patient cohort is the use of focal therapy, where the treatment is focussed on an identified dominant index lesion (DIL). This work aims to investigate the treatment parameters for focal SBRT of the prostate under which clinically acceptable rectal NTCP levels can be achieved. For each of 25 low risk CaP patients, a hypothetical 2 cc DIL was modeled in the right-posterior quadrant of the prostate, and was used to build a PTV as the target for SBRT simulation. An SBRT prescriptions of 41 Gy and 37 Gy in 5 fractions were chosen, corresponding to the boost levels used in previous CaP dose escalation studies. DVH data were exported and used to calculate rectal NTCP values based on the Lyman-Kutcher-Burman (LKB) model using the QUANTEC reccommended model parameters. Rectal NTCP dependence on DIL-to-rectum separation, dose level, and DIL volume were investigated. The final goal of this ongoing work is to create a map of the maximum allowable prescription dose for a given patient geometry that achieves a clinically acceptable rectal NTCP level.

  11. Characterization of the transport signals that mediate the nucleocytoplasmic traffic of low risk HPV11 E7

    Energy Technology Data Exchange (ETDEWEB)

    McKee, Courtney H.; Onder, Zeynep; Ashok, Aditya; Cardoso, Rebeca; Moroianu, Junona, E-mail: moroianu@bc.edu

    2013-08-15

    We previously discovered that nuclear import of low risk HPV11 E7 is mediated by its zinc-binding domain via a pathway that is independent of karyopherins/importins (Piccioli et al., 2010. Virology 407, 100–109). In this study we mapped and characterized a leucine-rich nuclear export signal (NES), {sub 76}IRQLQDLLL{sub 84}, within the zinc-binding domain that mediates the nuclear export of HPV11 E7 in a CRM1-dependent manner. We also identified a mostly hydrophobic patch {sub 65}VRLVV{sub 69} within the zinc-binding domain that mediates nuclear import of HPV11 E7 via hydrophobic interactions with the FG-repeats domain of Nup62. Substitutions of hydrophobic residues to alanine within the {sub 65}VRLVV{sub 69} sequence disrupt the nuclear localization of 11E7, whereas the R66A mutation has no effect. Overall the data support a model of nuclear entry of HPV11 E7 protein via hydrophobic interactions with FG nucleoporins at the nuclear pore complex. - Highlights: • HPV11 E7 has a leucine-rich nuclear export signal that mediates its nuclear export via CRM1. • HPV11 E7 interacts via its unique cNLS with the FG domain of Nup62. • Identification of a hydrophobic patch essential for nuclear localization of HPV11 E7.

  12. Characterization of the transport signals that mediate the nucleocytoplasmic traffic of low risk HPV11 E7

    International Nuclear Information System (INIS)

    McKee, Courtney H.; Onder, Zeynep; Ashok, Aditya; Cardoso, Rebeca; Moroianu, Junona

    2013-01-01

    We previously discovered that nuclear import of low risk HPV11 E7 is mediated by its zinc-binding domain via a pathway that is independent of karyopherins/importins (Piccioli et al., 2010. Virology 407, 100–109). In this study we mapped and characterized a leucine-rich nuclear export signal (NES), 76 IRQLQDLLL 84 , within the zinc-binding domain that mediates the nuclear export of HPV11 E7 in a CRM1-dependent manner. We also identified a mostly hydrophobic patch 65 VRLVV 69 within the zinc-binding domain that mediates nuclear import of HPV11 E7 via hydrophobic interactions with the FG-repeats domain of Nup62. Substitutions of hydrophobic residues to alanine within the 65 VRLVV 69 sequence disrupt the nuclear localization of 11E7, whereas the R66A mutation has no effect. Overall the data support a model of nuclear entry of HPV11 E7 protein via hydrophobic interactions with FG nucleoporins at the nuclear pore complex. - Highlights: • HPV11 E7 has a leucine-rich nuclear export signal that mediates its nuclear export via CRM1. • HPV11 E7 interacts via its unique cNLS with the FG domain of Nup62. • Identification of a hydrophobic patch essential for nuclear localization of HPV11 E7

  13. Incidence of low risk human papillomavirus in oral cancer: a real time PCR study on 278 patients.

    Science.gov (United States)

    Palmieri, A; Scapoli, L; Martinelli, M; Pezzetti, F; Girardi, A; Spinelli, G; Lucchese, A; Carinci, F

    2011-01-01

    Squamous cell carcinoma is the most frequent malignant tumour of the oral cavity. It is widely known that tobacco and alcohol consumption are the major causes of the development of oral squamous cell carcinoma (OSCC). The human papilloma virus infection has also been postulated as a risk factor for squamous cell carcinoma, although conflicting results have been reported. The aim of this study is to evaluate the presence of high-risk and low-risk type human papillomavirus in a large sample of squamous cell carcinoma limited to the oral cavity by means of quantitative real-time polymerase chain reaction. Data were obtained from 278 squamous cell carcinoma limited to oral cavity proper. Sequencing revealed that 5 samples were positive for HPV type 16, 5 for HPV type 11, and 1 for HPV type 6. Human papillomavirus 11 was detected in 5 tumours out of the 278 examined. The prevalence rate for Human papillomavirus 11 was 1.8% (C.I. 0.7-3.9). The matched case-controls analysis indicated that the prevalence among controls did not significantly differ with respect to cases and that Human papillomavirus 11 alone did not correlate with squamous cell carcinoma.

  14. Impaired Expression of Focal Adhesion Kinase in Mesenchymal Stromal Cells from Low-Risk Myelodysplastic Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Yuenv Wu

    2017-08-01

    Full Text Available The pathogenic role of mesenchymal stromal cells (MSCs in myelodysplastic syndromes (MDS development and progression has been investigated by numerous studies, yet, it remains controversial in some aspects (1, 2. In the present study, we found distinct features of MSCs from low-risk (LR-MDS stromal microenvironment as compared to those from healthy subjects. At the molecular level, focal adhesion kinase, a key tyrosine kinase in control of cell proliferation, survival, and adhesion process, was found profoundly suppressed in expression and activation in LR-MDS MSC. At a functional level, LR-MDS MSCs showed impaired growth and clonogenic capacity, which were independent of cellular senescence and apoptosis. The pro-adipogenic differentiation and attenuated osteogenic capacity along with reduced SDF-1 expression could be involved in creating an unfavorable microenvironment for hematopoiesis. In conclusion, our experiments support the theory that the stromal microenvironment is fundamentally altered in LR-MDS, and these preliminary data offer a new perspective on LR-MDS pathophysiology.

  15. Management of Adolescent Low-Risk Classical Hodgkin Lymphoma: Which Chemotherapy Backbone Gives the Best Chance of Omitting Radiotherapy Safely.

    Science.gov (United States)

    Algiraigri, Ali H; Essa, Mohammed F

    2016-03-01

    Even though more than 90% of adolescents with low-risk classical Hodgkin lymphoma (LRcHL) will be cured with first-line therapy, many will suffer serious late toxic effects from radiotherapy (RT). The goals for care have shifted toward minimizing late toxic effects without compromising the outstanding cure rates by adapting a risk and response-based therapy. Recent published and ongoing randomized clinical trials, using functional imaging, may allow for better identification of those patients for whom RT may be safely omitted while maintaining excellent cure rates. To evaluate the best chemotherapy regimens with a reasonable toxicity profile and that are expected to have a high chance of omitting RT based on a response-directed therapy while maintaining high cure rates, a mini review was conducted of the recent clinical trials in pediatric and adult LRcHL. The UK RAPID trial chemotherapy backbone (3 × ABVD) followed by a response-based positron emission tomography scan offers up to a 75% chance of safely omitting RT without compromising the cure rate, which remained well above 90%.

  16. Comparison of the MASCC and CISNE scores for identifying low-risk neutropenic fever patients: analysis of data from three emergency departments of cancer centers in three continents.

    Science.gov (United States)

    Ahn, Shin; Rice, Terry W; Yeung, Sai-Ching J; Cooksley, Tim

    2018-05-01

    Patients with febrile neutropenia are a heterogeneous group with a minority developing serious medical complications. Outpatient management of low-risk febrile neutropenia has been shown to be safe and cost-effective. Scoring systems, such as the Multinational Association for Supportive Care in Cancer (MASCC) score and Clinical Index of Stable Febrile Neutropenia (CISNE), have been developed and validated to identify low-risk patients. We aimed to compare the performance of these two scores in identifying low-risk febrile neutropenic patients. We performed a pooled analysis of patients presenting with febrile neutropenia to three tertiary cancer emergency centers in the USA, UK, and South Korea in 2015. The primary outcome measures were the occurrence of serious complications. Admission to an intensive care unit (ICU) and 30-day mortality were secondary outcomes. The predictive performance of each score was analyzed. Five hundred seventy-one patients presented with febrile neutropenia. With MASCC risk index, 508 (89.1%) were classified as low-risk febrile neutropenia, compared to 60 (10.5%) with CISNE classification. Overall, the MASCC score had a greater discriminatory power in the detection of low-risk patients than the CISNE score (AUC 0.772, 95% CI 0.726-0.819 vs. 0.681, 95% CI 0.626-0.737, p = 0.0024). Both MASCC and CISNE scores have reasonable discriminatory value in predicting patients with low-risk febrile neutropenia. Risk scores should be used in conjunction with clinical judgment for the identification of patients suitable for outpatient management of neutropenic fever. Developing more accurate scores, validated in prospective settings, will be useful in facilitating more patients being managed in an outpatient setting.

  17. Somatic cancer variant curation and harmonization through consensus minimum variant level data

    Directory of Open Access Journals (Sweden)

    Deborah I. Ritter

    2016-11-01

    Full Text Available Abstract Background To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG of the Clinical Genome Resource (ClinGen, in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD. MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods We developed MVLD through a consensus approach by i reviewing clinical actionability interpretations from institutions participating in the WG, ii conducting extensive literature search of clinical somatic interpretation schemas, and iii survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP, can be incorporated into MVLD. Results Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of

  18. Synthesis of spatially variant lattices.

    Science.gov (United States)

    Rumpf, Raymond C; Pazos, Javier

    2012-07-02

    It is often desired to functionally grade and/or spatially vary a periodic structure like a photonic crystal or metamaterial, yet no general method for doing this has been offered in the literature. A straightforward procedure is described here that allows many properties of the lattice to be spatially varied at the same time while producing a final lattice that is still smooth and continuous. Properties include unit cell orientation, lattice spacing, fill fraction, and more. This adds many degrees of freedom to a design such as spatially varying the orientation to exploit directional phenomena. The method is not a coordinate transformation technique so it can more easily produce complicated and arbitrary spatial variance. To demonstrate, the algorithm is used to synthesize a spatially variant self-collimating photonic crystal to flow a Gaussian beam around a 90° bend. The performance of the structure was confirmed through simulation and it showed virtually no scattering around the bend that would have arisen if the lattice had defects or discontinuities.

  19. Different Variants of Fundamental Portfolio

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    Tarczyński Waldemar

    2014-06-01

    Full Text Available The paper proposes the fundamental portfolio of securities. This portfolio is an alternative for the classic Markowitz model, which combines fundamental analysis with portfolio analysis. The method’s main idea is based on the use of the TMAI1 synthetic measure and, in limiting conditions, the use of risk and the portfolio’s rate of return in the objective function. Different variants of fundamental portfolio have been considered under an empirical study. The effectiveness of the proposed solutions has been related to the classic portfolio constructed with the help of the Markowitz model and the WIG20 market index’s rate of return. All portfolios were constructed with data on rates of return for 2005. Their effectiveness in 2006- 2013 was then evaluated. The studied period comprises the end of the bull market, the 2007-2009 crisis, the 2010 bull market and the 2011 crisis. This allows for the evaluation of the solutions’ flexibility in various extreme situations. For the construction of the fundamental portfolio’s objective function and the TMAI, the study made use of financial and economic data on selected indicators retrieved from Notoria Serwis for 2005.

  20. Ultrasonographic imaging of papillary thyroid carcinoma variants

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    Shin, Jung Hee [Dept. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2017-04-15

    Ultrasonography (US) is routinely used to evaluate thyroid nodules. The US features of papillary thyroid carcinoma (PTC), the most common thyroid malignancy, include hypoechogenicity, spiculated/microlobulated margins, microcalcifications, and a nonparallel orientation. However, many PTC variants have been identified, some of which differ from the classic type of PTC in terms of biological behavior and clinical outcomes. This review describes the US features and clinical implications of the variants of PTC. With the introduction of active surveillance replacing immediate biopsy or surgical treatment of indolent, small PTCs, an understanding of the US characteristics of PTC variants will facilitate the individualized management of patients with PTC.

  1. Long-Term Outcomes From a Prospective Trial of Stereotactic Body Radiotherapy for Low-Risk Prostate Cancer

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    King, Christopher R.; Brooks, James D.; Gill, Harcharan; Presti, Joseph C.

    2012-01-01

    Purpose: Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The results of a prospective trial of stereotactic body radiotherapy (SBRT) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented. Methods and Materials: From 2003 through 2009, 67 patients with clinically localized low-risk prostate cancer were enrolled. Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology. No patient received hormone therapy. Patient self-reported bladder and rectal toxicities were graded on the Radiation Therapy Oncology Group scale (RTOG). Results: Median follow-up was 2.7 years. There were no grade 4 toxicities. Radiation Therapy Oncology Group Grade 3, 2, and 1 bladder toxicities were seen in 3% (2 patients), 5% (3 patients), and 23% (13 patients) respectively. Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity. Urinary incontinence, complete obstruction, or persistent hematuria was not observed. Rectal Grade 3, 2, and 1 toxicities were seen in 0, 2% (1 patient), and 12.5% (7 patients), respectively. Persistent rectal bleeding was not observed. Low-grade toxicities were substantially less frequent with QOD vs. QD dose regimen (p = 0.001 for gastrointestinal and p = 0.007 for genitourinary). There were two prostate-specific antigen (PSA), biopsy-proven failures with negative metastatic workup. Median PSA at follow-up was 0.5 ± 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94% (95% confidence interval, 85%–102%). Conclusion: Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. PSA relapse-free survival compares favorably with other definitive treatments. The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer.

  2. Long-Term Outcomes From a Prospective Trial of Stereotactic Body Radiotherapy for Low-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, Christopher R., E-mail: crking@mednet.ucla.edu [Departments of Radiation Oncology and Urology, University of California Los Angeles School of Medicine, Los Angeles, CA (United States); Brooks, James D.; Gill, Harcharan; Presti, Joseph C. [Department of Urology, Stanford University School of Medicine, Stanford, CA (United States)

    2012-02-01

    Purpose: Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The results of a prospective trial of stereotactic body radiotherapy (SBRT) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented. Methods and Materials: From 2003 through 2009, 67 patients with clinically localized low-risk prostate cancer were enrolled. Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology. No patient received hormone therapy. Patient self-reported bladder and rectal toxicities were graded on the Radiation Therapy Oncology Group scale (RTOG). Results: Median follow-up was 2.7 years. There were no grade 4 toxicities. Radiation Therapy Oncology Group Grade 3, 2, and 1 bladder toxicities were seen in 3% (2 patients), 5% (3 patients), and 23% (13 patients) respectively. Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity. Urinary incontinence, complete obstruction, or persistent hematuria was not observed. Rectal Grade 3, 2, and 1 toxicities were seen in 0, 2% (1 patient), and 12.5% (7 patients), respectively. Persistent rectal bleeding was not observed. Low-grade toxicities were substantially less frequent with QOD vs. QD dose regimen (p = 0.001 for gastrointestinal and p = 0.007 for genitourinary). There were two prostate-specific antigen (PSA), biopsy-proven failures with negative metastatic workup. Median PSA at follow-up was 0.5 {+-} 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94% (95% confidence interval, 85%-102%). Conclusion: Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. PSA relapse-free survival compares favorably with other definitive treatments. The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer.

  3. Maternal Medical Complexity: Impact on Prenatal Health Care Spending among Women at Low Risk for Cesarean Section.

    Science.gov (United States)

    Cunningham, Shayna D; Herrera, Carolina; Udo, Ifeyinwa E; Kozhimannil, Katy B; Barrette, Eric; Magriples, Urania; Ickovics, Jeannette R

    Obstetric procedures are among the most expensive health care services, yet relatively little is known about health care spending among pregnant women, particularly the commercially-insured. The objective of this study was to examine the association between maternal medical complexity, as a result of having one or more comorbid conditions, and health care spending during the prenatal period among a national sample of 95,663 commercially-insured women at low risk for cesarean delivery. We conducted secondary analyses of 2010-2011 inpatient, outpatient, and professional claims for health care services from the Health Care Cost Institute. Allowed charges were summed for the prenatal and childbirth periods. Ordinary least squares regressions tested associations between maternal health conditions and health care expenditures during pregnancy. Thirty-four percent of pregnant women had one or more comorbidities; 8% had two or more. Pregnant women with one or more comorbidities had significantly higher allowed charges than those without comorbidities (p prenatal period was nearly three times higher for women with preexisting diabetes compared with women with no comorbid conditions. Average levels of prenatal period spending associated with maternal comorbidities were similar for women who had vaginal and cesarean deliveries. Patient characteristics accounted for 30% of the variance in prenatal period expenditures. The impact of maternal comorbidities, and in particular preexisting diabetes, on prenatal care expenditures should be taken into account as provider payment reforms, such as pay-for performance incentives and bundled payments for episodes of care, extend to maternal and child health-related services. Copyright © 2017 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  4. Energy density at a buffet-style lunch differs for adolescents born at high and low risk of obesity.

    Science.gov (United States)

    Kral, Tanja V E; Stunkard, Albert J; Berkowitz, Robert I; Stettler, Nicolas; Stallings, Virginia A; Kabay, April; Faith, Myles S

    2009-12-01

    The energy density (ED; kcal/g) of foods, when manipulated in the laboratory, affects short-term energy intake. The aim of this study was to examine if, when given a choice, dietary ED (foods only) and energy intake (expressed as a percentage of subjects' estimated daily energy requirement; EER) at a self-selected, single meal differ for teens born with a different familial predisposition to obesity and as a function of their sex. Subjects (13 males, 17 females) were 12years of age and born at high risk (HR; n=15) or low risk (LR; n=15) for obesity based on maternal pre-pregnancy body mass index (BMI; kg/m(2)). The buffet meal, served for lunch and consumed ad libitum, consisted of a variety of foods and beverages with a range in ED. HR subjects consumed a more energy-dense meal (foods only) than LR subjects (1.84 vs. 1.42kcal/g; P=0.02) and males consumed a more energy-dense meal than females (1.83 vs. 1.43kcal/g; P=0.03). Total energy intake, when expressed as a percentage of subjects' daily EER, did not differ between HR and LR subjects (42% vs. 33%; P=0.16). Males, compared to females, consumed ~59% more energy from foods and beverages during the meal (46 vs. 29%; P=0.008). During a single multi-item lunch meal, teens with a familial predisposition to obesity and males, independent of their obesity risk status, self-selected a more energy-dense meal. Familial risk for obesity, through either genetic or environmental pathways, may facilitate a more energy-dense diet.

  5. Using low-risk factors to generate non-integrated human induced pluripotent stem cells from urine-derived cells.

    Science.gov (United States)

    Wang, Linli; Chen, Yuehua; Guan, Chunyan; Zhao, Zhiju; Li, Qiang; Yang, Jianguo; Mo, Jian; Wang, Bin; Wu, Wei; Yang, Xiaohui; Song, Libing; Li, Jun

    2017-11-02

    Because the lack of an induced pluripotent stem cell (iPSC) induction system with optimal safety and efficiency limits the application of these cells, development of such a system is important. To create such an induction system, we screened a variety of reprogrammed plasmid combinations and multiple compounds and then verified the system's feasibility using urine cells from different individuals. We also compared large-scale iPSC chromosomal variations and expression of genes associated with genomic stability between this system and the traditional episomal system using karyotype and quantitative reverse transcription polymerase chain reaction analyses. We developed a high-efficiency episomal system, the 6F/BM1-4C system, lacking tumorigenic factors for human urine-derived cell (hUC) reprogramming. This system includes six low-risk factors (6F), Oct4, Glis1, Klf4, Sox2, L-Myc, and the miR-302 cluster. Transfected hUCs were treated with four compounds (4C), inhibitor of lysine-demethylase1, methyl ethyl ketone, glycogen synthase kinase 3 beta, and histone deacetylase, within a short time period. Comparative analysis revealed significantly decreased chromosomal variation in iPSCs and significantly increased Sirt1 expression compared with iPSCs induced using the traditional episomal system. The 6F/BM1-4C system effectively induces reprogramming of urine cells in samples obtained from different individuals. iPSCs induced using the 6F/BM1-4C system are more stable at the cytogenetic level and have potential value for clinical application.

  6. The effect of ABO blood incompatibility on corneal transplant failure in conditions with low-risk of graft rejection.

    Science.gov (United States)

    Dunn, Steven P; Stark, Walter J; Stulting, R Doyle; Lass, Jonathan H; Sugar, Alan; Pavilack, Mark A; Smith, Patricia W; Tanner, Jean Paul; Dontchev, Mariya; Gal, Robin L; Beck, Roy W; Kollman, Craig; Mannis, Mark J; Holland, Edward J

    2009-03-01

    To determine whether corneal graft survival over a 5-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs dystrophy or pseudophakic corneal edema, conditions at low-risk for graft rejection. Multi-center prospective, double-masked, clinical trial. ABO blood group compatibility was determined for 1,002 donors and recipients. During a 5-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were attributable to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects. ABO donor-recipient incompatibility was not associated with graft failure attributable to any cause including graft failure because of rejection, or with the occurrence of a rejection episode. The 5-year cumulative incidence of graft failure attributable to rejection was 32 (6%) for recipients with ABO recipient-donor compatibility and 12 (4%) for those with ABO incompatibility (hazard ratio, 0.65; 95% confidence interval, 0.33 to 1.25; P = .20). The 5-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 64 (12%) for ABO compatible compared with 25 (8%) for ABO incompatible cases (P = .09). Among clear grafts at 5 years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases. In patients undergoing penetrating keratoplasty for Fuchs dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure attributable to graft rejection.

  7. A Comparison of Postpartum Depression among Low-risk-pregnant Women with Emotion- and Problem-focused Coping Strategies

    Directory of Open Access Journals (Sweden)

    Habibeh Salehi

    2013-03-01

    Full Text Available Background and Objectives: Postpartum depression is one of most important health problems in women. This study was performed with the purpose of comparing the frequency of postpartum depression in pregnant women with emotion and problem-focused coping strategies. Methods: This study was conducted as a prospective cohort study on 200 pregnant women with stress (low and high levels. The samples were pregnant women referred to all health-treatment, centers of Ardabil, which were selected using a multi-stage sampling method; and according to coping strategy, they were divided into two groups: emotion-focused and problem-focused. Low-risk pregnant women completed questionnaires about demographic characteristics, perceived stress, and Billings and Moos coping strategies in the 38th to 42th week of their pregnancy, and completed the Edinburgh depression scale in the 3th to 4th weeks after childbirth. Data were analyzed using chi 2 and t tests. p<0.05 considered significant.Results: In this study, 170 participant women (85% used emotion-focused strategy and 30 women (15% used problem-focused strategy. Frequency of postpartum depression was 6.7% in the problem-focused group and 8.2% in the emotion-focused group. There was no significant difference in the frequency of postpartum depression between women with the problem- and emotion-focused strategies. Relative risk for postpartum depression was 1.2 times more among the women used emotion-focused strategy than women used problem-focused strategy (p<0.05.Conclusion: According to the results of this study, there was no significant relationship between postpartum depression and the two emotion-focused and problem-focused coping strategies. This can be due to high influence of postpartum specific endocrine factors in the etiology of this type of depression compared to other depressions.

  8. Planned home compared with planned hospital births in the Netherlands: intrapartum and early neonatal death in low-risk pregnancies.

    Science.gov (United States)

    van der Kooy, Jacoba; Poeran, Jashvant; de Graaf, Johanna P; Birnie, Erwin; Denktasş, Semiha; Steegers, Eric A P; Bonsel, Gouke J

    2011-11-01

    The purpose of our study was to compare the intrapartum and early neonatal mortality rate of planned home birth with planned hospital birth in community midwife-led deliveries after case mix adjustment. The perinatal outcome of 679,952 low-risk women was obtained from the Netherlands Perinatal Registry (2000-2007). This group represents all women who had a choice between home and hospital birth. Two different analyses were performed: natural prospective approach (intention-to-treat-like analysis) and perfect guideline approach (per-protocol-like analysis). Unadjusted and adjusted odds ratios (ORs) were calculated. Case mix was based on the presence of at least one of the following: congenital abnormalities, small for gestational age, preterm birth, or low Apgar score. We also investigated the potential risk role of intended place of birth. Multivariate stepwise logistic regression was used to investigate the potential risk role of intended place of birth. Intrapartum and neonatal death at 0-7 days was observed in 0.15% of planned home compared with 0.18% in planned hospital births (crude relative risk 0.80, 95% confidence interval [CI] 0.71-0.91). After case mix adjustment, the relation is reversed, showing nonsignificant increased mortality risk of home birth (OR 1.05, 95% CI 0.91-1.21). In certain subgroups, additional mortality may arise at home if risk conditions emerge at birth (up to 20% increase). Home birth, under routine conditions, is generally not associated with increased intrapartum and early neonatal death, yet in subgroups, additional risk cannot be excluded.

  9. Role of prostate specific antigen and immediate confirmatory biopsy in predicting progression during active surveillance for low risk prostate cancer.

    Science.gov (United States)

    Adamy, Ari; Yee, David S; Matsushita, Kazuhito; Maschino, Alexandra; Cronin, Angel; Vickers, Andrew; Guillonneau, Bertrand; Scardino, Peter T; Eastham, James A

    2011-02-01

    We evaluated predictors of progression after starting active surveillance, especially the role of prostate specific antigen and immediate confirmatory prostate biopsy. A total of 238 men with prostate cancer met active surveillance eligibility criteria and were analyzed for progression with time. Cox proportional hazards regression was used to evaluate predictors of progression. Progression was evaluated using 2 definitions, including no longer meeting 1) full and 2) modified criteria, excluding prostate specific antigen greater than 10 ng/ml as a criterion. Using full criteria 61 patients progressed during followup. The 2 and 5-year progression-free probability was 80% and 60%, respectively. With prostate specific antigen included in progression criteria prostate specific antigen at confirmatory biopsy (HR 1.29, 95% CI 1.14-1.46, p <0.0005) and positive confirmatory biopsy (HR 1.75, 95% CI 1.01-3.04, p = 0.047) were independent predictors of progression. Of the 61 cases 34 failed due to increased prostate specific antigen, including only 5 with subsequent progression by biopsy criteria. When prostate specific antigen was excluded from progression criteria, only 32 cases progressed, and 2 and 5-year progression-free probability was 91% and 76%, respectively. Using modified criteria as an end point positive confirmatory biopsy was the only independent predictor of progression (HR 3.16, 95% CI 1.41-7.09, p = 0.005). Active surveillance is feasible in patients with low risk prostate cancer and most patients show little evidence of progression within 5 years. There is no clear justification for treating patients in whom prostate specific antigen increases above 10 ng/ml in the absence of other indications of tumor progression. Patients considering active surveillance should undergo confirmatory biopsy to better assess the risk of progression. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Prostate MRI findings in patients treated for testosterone deficiency while on active surveillance for low-risk prostate cancer

    Science.gov (United States)

    Hashimoto, Takeshi; Rahul, Krishnan; Takeda, Toshikazu; Benfante, Nicole; Mulhall, John P.; Hricak, Hedvig; Eastham, James A.; Vargas, Hebert Alberto

    2017-01-01

    Objective To investigate the multiparametric prostate magnetic resonance imaging (mpMRI) findings in patients treated with testosterone replacement therapy (TRT) while on active surveillance (AS) for low-risk prostate cancer. Methods We retrospectively reviewed 12 patients who underwent mpMRI before and after TRT while on AS. Changes in serum testosterone level, prostate specific antigen (PSA), prostate biopsy findings, prostate volume and Prostate Imaging Reporting and Data System Version 2 (PI-RADSv2) score before and after TRT were summarized. Results Following TRT, there was a significant increase in serum testosterone (516.5 ng/dl vs. 203.0 ng/dl), PSA (4.2 ng/ml vs. 3.3 ng/ml) and prostate volume (55.2 cm3 vs. 39.4 cm3). Two patients had biopsy progression during the study periods. The PI-RADSv2 scores before and after TRT were unchanged in 10/12 patients; none of these demonstrated biopsy progression on post TRT. The PI-RADSv2 scores increased after TRT in 2/12 patients; both showed Gleason score upgrade on follow-up biopsy. One of these two patients underwent radical treatment due to clinical progression. The area under the curve calculated from PI-RADSv2 score after TRT was 0.90, which was better than that calculated from post TRT PSA level (0.48). Conclusions After TRT, mpMRI findings remained stable in patients without biopsy progression, while PI-RADSv2 score increase was identified in patients with Gleason score upgrade on follow-up biopsy. PMID:27665357

  11. Can Single Positive Core Prostate Cancer at biopsy be Considered a Low-Risk Disease after Radical Prostatectomy?

    Directory of Open Access Journals (Sweden)

    Ricardo Kupka da Silva

    2013-12-01

    Full Text Available Purpose Single positive core in a prostate biopsy is usually associated with indolent prostate cancer (PCa and is one of the active surveillance (AS inclusion criteria. We investigated whether single positive core PCa at biopsy could define an archetype of low-risk disease. Materials and Methods A total of 1320 consecutive patients were enrolled. Among them, 249 patients with single positive core PCa were followed up, and the clinical and pathological parameters influencing prognosis were analyzed. Results Out of the 249 patients, 172 (69.0% had pathological findings ≥ pT2c and 87 (34.9% had an undergraded Gleason Score (GS based on the biopsy. Positive surgical margins (PSMs, extraprostatic extension (EPE and seminal vesicle invasion (SVI were found in 20.8%, 10.0% and 6.0% of patients, respectively. In a comparative analysis, we found that the PSA level, prostate weight and number of cores at biopsy are essential to correctly predict an indolent PCa. A total of 125 patients (67.3% with nonpalpable tumors became high-risk tumors (pT2c-T3. Analyzing only nonpalpable tumors with a GS of 6 at biopsy (156 patients, we noted that 106 (67.9% of cT1 progressed from cT1c to pT2c-pT3. Conclusions Single core PCa have clinically significant disease in the Radical Prostatectomy specimens, with considerable rates of overgrading for the GS, pT2c-pT3, PSMs, EPE and SVI. The treatment plan must be evaluated individually for patients with single core PCa and must take into account other prognostic factors when determining whether a patient should be managed with AS.

  12. Alcohol consumption and low-risk drinking guidelines among adults: a cross-sectional analysis from Alberta's Tomorrow Project.

    Science.gov (United States)

    Brenner, Darren R; Haig, Tiffany R; Poirier, Abbey E; Akawung, Alianu; Friedenreich, Christine M; Robson, Paula J

    2017-12-01

    Moderate to heavy alcohol consumption is a risk factor for all-cause mortality and cancer incidence. Although cross-sectional data are available through national surveys, data on alcohol consumption in Alberta from a large prospective cohort were not previously available. The goal of these analyses was to characterize the levels of alcohol consumption among adults from the Alberta's Tomorrow Project in the context of cancer prevention guidelines. Furthermore, we conducted analyses to examine the relationships between alcohol consumption and other high-risk or risk-related behaviours. Between 2001 and 2009, 31 072 men and women aged 35 to 69 years were enrolled into Alberta's Tomorrow Project, a large provincial cohort study. Data concerning alcohol consumption in the past 12 months were obtained from 26 842 participants who completed self-administered health and lifestyle questionnaires. We conducted cross-sectional analyses on daily alcohol consumption and cancer prevention guidelines for alcohol use in relation to sociodemographic factors. We also examined the combined prevalence of alcohol consumption and tobacco use, obesity and comorbidities. Approximately 14% of men and 12% of women reported alcohol consumption exceeding recommendations for cancer prevention. Higher alcohol consumption was reported in younger age groups, urban dwellers, those with higher incomes and those who consumed more red meat. Moreover, volume of daily alcohol consumption was positively associated with current tobacco use in both men and women. Overall, men were more likely to fall in the moderate and high-risk behavioural profiles and show higher daily alcohol consumption patterns compared to women. Despite public health messages concerning the adverse impact of alcohol consumption, a sizeable proportion of Alberta's Tomorrow Project participants consumed alcohol in excess of cancer prevention recommendations. Continued strategies to promote low-risk drinking among those who choose to

  13. Preferences for a third-trimester ultrasound scan in a low-risk obstetric population: a discrete choice experiment.

    Science.gov (United States)

    Lynn, Fiona A; Crealey, Grainne E; Alderdice, Fiona A; McElnay, James C

    2015-10-01

    Establish maternal preferences for a third-trimester ultrasound scan in a healthy, low-risk pregnant population. Cross-sectional study incorporating a discrete choice experiment. A large, urban maternity hospital in Northern Ireland. One hundred and forty-six women in their second trimester of pregnancy. A discrete choice experiment was designed to elicit preferences for four attributes of a third-trimester ultrasound scan: health-care professional conducting the scan, detection rate for abnormal foetal growth, provision of non-medical information, cost. Additional data collected included age, marital status, socio-economic status, obstetric history, pregnancy-specific stress levels, perceived health and whether pregnancy was planned. Analysis was undertaken using a mixed logit model with interaction effects. Women's preferences for, and trade-offs between, the attributes of a hypothetical scan and indirect willingness-to-pay estimates. Women had significant positive preference for higher rate of detection, lower cost and provision of non-medical information, with no significant value placed on scan operator. Interaction effects revealed subgroups that valued the scan most: women experiencing their first pregnancy, women reporting higher levels of stress, an adverse obstetric history and older women. Women were able to trade on aspects of care and place relative importance on clinical, non-clinical outcomes and processes of service delivery, thus highlighting the potential of using health utilities in the development of services from a clinical, economic and social perspective. Specifically, maternal preferences exhibited provide valuable information for designing a randomized trial of effectiveness and insight for clinical and policy decision makers to inform woman-centred care. © 2013 Blackwell Publishing Ltd.

  14. Maternal hormone levels and risk of cryptorchism among populations at high and low risk of testicular germ cell tumors.

    Science.gov (United States)

    McGlynn, Katherine A; Graubard, Barry I; Nam, Jun-Mo; Stanczyk, Frank Z; Longnecker, Matthew P; Klebanoff, Mark A

    2005-07-01

    Cryptorchism is one of the few well-described risk factors for testicular cancer. It has been suggested that both conditions are related to increased in utero estrogen exposure. The evidence supporting the "estrogen hypothesis" has been inconsistent, however. An alternative hypothesis suggests that higher in utero androgen exposure may protect against the development of cryptorchism and testicular cancer. In order to examine both hypotheses, we studied maternal hormone levels in two populations at diverse risks of testicular cancer; Black Americans (low-risk) and White Americans (high-risk). The study population of 200 mothers of cryptorchid sons and 200 mothers of noncryptorchid sons was nested within the Collaborative Perinatal Project, a cohort study of pregnant women and their children. Third trimester serum levels of estradiol (total, free, bioavailable), estriol, testosterone (total, free, bioavailable), sex hormone-binding globulin, alpha-fetoprotein, and the ratios of estradiols to testosterones were compared between the case and control mothers. The results found no significant differences in the levels of testosterone (total, free, bioavailable), alpha-fetoprotein, sex hormone-binding globulin, or in the ratios of estrogens to androgens. Total estradiol, however, was significantly lower in the cases versus the controls (P = 0.03) among all mothers and, separately, among White mothers (P = 0.05). Similarly, estriol was significantly lower among all cases (P = 0.05) and among White cases (P = 0.05). These results do not support either the estrogen or the androgen hypothesis. Rather, lower estrogens in case mothers may indicate that a placental defect increases the risk of cryptorchism and, possibly, testicular cancer.

  15. Attractive toxic sugar baits: Control of mosquitoes with the low risk active ingredient dinotefuran and potential impacts on non-target organisms in Morocco

    Science.gov (United States)

    We evaluated the efficacy of ATSB in the laboratory and the field with the low risk active ingredient dinotefuran against mosquito populations. Assays indicated that dinotefuran in solution with the sugar baits was ingested and resulted in high mortality of female Culex quinquefasciatus and Aedes a...

  16. Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

    NARCIS (Netherlands)

    de Bont, ESJM; Vellenga, E; Swaanenburg, JCJM; Fidler, [No Value; Visser-van Brummen, PJ; Kamps, WA

    The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. Ih this study plasma

  17. Ultrasound assessment of placental function: the effectiveness of placental biometry in a low-risk population as a predictor of a small for gestational age neonate.

    LENUS (Irish Health Repository)

    McGinty, Patricia

    2012-07-01

    The aims of the study were to establish reference ranges for placental length and thickness in a low-risk obstetric population and to assess the likelihood of a small for gestational age (SGA) neonate on the basis of placental length at 18-24 weeks\\' gestation.

  18. Risk score for identifying adults with CSF pleocytosis and negative CSF Gram stain at low risk for an urgent treatable cause

    NARCIS (Netherlands)

    Hasbun, Rodrigo; Bijlsma, Merijn; Brouwer, Matthijs C.; Khoury, Nabil; Hadi, Christiane M.; van der Ende, Arie; Wootton, Susan H.; Salazar, Lucrecia; Hossain, Md Monir; Beilke, Mark; van de Beek, Diederik

    2013-01-01

    We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Patients with CSF pleocytosis and a negative CSF Gram stain were stratified into a prospective derivation (n = 193)

  19. Perinatal and maternal outcomes by planned place of birth for healthy women with low risk pregnancies: the Birthplace in England national prospective cohort study.

    NARCIS (Netherlands)

    Brocklehurst, P.; Kwee, A.; Birthplace in England Collaborative Group

    2011-01-01

    Objective: To compare perinatal outcomes, maternal outcomes, and interventions in labour by planned place of birth at the start of care in labour for women with low risk pregnancies. Design: Prospective cohort study. Setting: England: all NHS trusts providing intrapartum care at home,

  20. Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

    NARCIS (Netherlands)

    de Bont, ESJM; Vellenga, E; Swaanenburg, JCJM; Fidler, [No Value; Visser-van Brummen, PJ; Kamps, WA

    1999-01-01

    The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. Ih this study plasma

  1. Predictive value of general movements' quality in low-risk infants for minor neurological dysfunction and behavioural problems at preschool age

    NARCIS (Netherlands)

    Bennema, Anne N; Schendelaar, Pamela; Seggers, Jorien; Haadsma, Maaike L; Heineman, Maas Jan; Hadders-Algra, Mijna

    Background: General movement (GM) assessment is a well-established tool to predict cerebral palsy in high-risk infants. Little is known on the predictive value of GM assessment in low-risk populations. Aims: To assess the predictive value of GM quality in early infancy for the development of the

  2. Preventing Preterm Birth with Progesterone in Women with a Short Cervical Length from a Low-Risk Population: A Multicenter Double-Blind Placebo-Controlled Randomized Trial

    NARCIS (Netherlands)

    van Os, M.A.; van der Ven, A.J.; Kleinrouweler, C.E.; Schuit, E.; Kazemier, B.M.; Verhoeven, C.J.M.; de Miranda, E.; van Wassenaer-Leemhuis, A.G.; Sikkema, J.M.; Woiski, M.D.; Bossuyt, P.M.; Pajkrt, E.; de Groot, C.J.M.; Mol, B.W.J.; Haak, M.C.

    2015-01-01

    Objective The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth (PTB) in low-risk pregnant women with a short cervical length (CL). Study Design Women with a singleton pregnancy without a history of PTB

  3. RAGE splicing variants in mammals.

    Science.gov (United States)

    Sterenczak, Katharina Anna; Nolte, Ingo; Murua Escobar, Hugo

    2013-01-01

    The receptor for advanced glycation end products (RAGE) is a multiligand receptor of environmental stressors which plays key roles in pathophysiological processes, including immune/inflammatory disorders, Alzheimer's disease, diabetic arteriosclerosis, tumorigenesis, and metastasis. Besides the full-length RAGE protein in humans nearly 20 natural occurring RAGE splicing variants were described on mRNA and protein level. These naturally occurring isoforms are characterized by either N-terminally or C-terminally truncations and are discussed as possible regulators of the full-length RAGE receptor either by competitive ligand binding or by displacing the full-length protein in the membrane. Accordingly, expression deregulations of the naturally occurring isoforms were supposed to have significant effect on RAGE-mediated disorders. Thereby the soluble C-truncated RAGE isoforms present in plasma and tissues are the mostly focused isoforms in research and clinics. Deregulations of the circulating levels of soluble RAGE forms were reported in several RAGE-associated pathological disorders including for example atherosclerosis, diabetes, renal failure, Alzheimer's disease, and several cancer types. Regarding other mammalian species, the canine RAGE gene showed high similarities to the corresponding human structures indicating RAGE to be evolutionary highly conserved between both species. Similar to humans the canine RAGE showed a complex and extensive splicing activity leading to a manifold pattern of RAGE isoforms. Due to the similarities seen in several canine and human diseases-including cancer-comparative structural and functional analyses allow the development of RAGE and ligand-specific therapeutic approaches beneficial for human and veterinary medicine.

  4. Isolation of a variant of Candida albicans.

    Science.gov (United States)

    Buckley, H R; Price, M R; Daneo-Moore, L

    1982-01-01

    During the course of Candida albicans antigen production, a variant of this organism was encountered which did not produce hyphae at 37 degrees C. Presented here are some of the characteristics of this variant. It produces hyphae at 25 degrees C on cornmeal agar and synthetic medium plus N-acetylglucosamine and Tween 80. At 37 degrees C, it does not produce hyphae on these media, although C. albicans normally does produce hyphae under these circumstances. In liquid synthetic medium, this variant does not produce hyphae at 37 degrees C. The variant strain was analyzed for DNA, RNA, protein content, and particle size. After 50 to 70 h in balanced exponential-phase growth, particle size distribution was narrow, and there were no differences in the DNA, RNA, or protein content per particle in the two strains. When balanced exponential-phase cultures were brought into stationary phase, both strains contained the same amount of DNA per cell. Images PMID:6752021

  5. Isolation of a variant of Candida albicans.

    Science.gov (United States)

    Buckley, H R; Price, M R; Daneo-Moore, L

    1982-09-01

    During the course of Candida albicans antigen production, a variant of this organism was encountered which did not produce hyphae at 37 degrees C. Presented here are some of the characteristics of this variant. It produces hyphae at 25 degrees C on cornmeal agar and synthetic medium plus N-acetylglucosamine and Tween 80. At 37 degrees C, it does not produce hyphae on these media, although C. albicans normally does produce hyphae under these circumstances. In liquid synthetic medium, this variant does not produce hyphae at 37 degrees C. The variant strain was analyzed for DNA, RNA, protein content, and particle size. After 50 to 70 h in balanced exponential-phase growth, particle size distribution was narrow, and there were no differences in the DNA, RNA, or protein content per particle in the two strains. When balanced exponential-phase cultures were brought into stationary phase, both strains contained the same amount of DNA per cell.

  6. Genetic variants of ghrelin in metabolic disorders.

    Science.gov (United States)

    Ukkola, Olavi

    2011-11-01

    An increasing understanding of the role of genes in the development of obesity may reveal genetic variants that, in combination with conventional risk factors, may help to predict an individual's risk for developing metabolic disorders. Accumulating evidence indicates that ghrelin plays a role in regulating food intake and energy homeostasis and it is a reasonable candidate gene for obesity-related co-morbidities. In cross-sectional studies low total ghrelin concentrations and some genetic polymorphisms of ghrelin have been associated with obesity-associated diseases. The present review highlights many of the important problems in association studies of genetic variants and complex diseases. It is known that population-specific differences in reported associations exist. We therefore conclude that more studies on variants of ghrelin gene are needed to perform in different populations to get deeper understanding on the relationship of ghrelin gene and its variants to obesity. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. TREM2 Variants in Alzheimer's Disease

    Science.gov (United States)

    Guerreiro, Rita; Wojtas, Aleksandra; Bras, Jose; Carrasquillo, Minerva; Rogaeva, Ekaterina; Majounie, Elisa; Cruchaga, Carlos; Sassi, Celeste; Kauwe, John S.K.; Younkin, Steven; Hazrati, Lilinaz; Collinge, John; Pocock, Jennifer; Lashley, Tammaryn; Williams, Julie; Lambert, Jean-Charles; Amouyel, Philippe; Goate, Alison; Rademakers, Rosa; Morgan, Kevin; Powell, John; St. George-Hyslop, Peter; Singleton, Andrew; Hardy, John

    2013-01-01

    BACKGROUND Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia. METHODS We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice. RESULTS We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P = 0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P = 0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease. CONCLUSIONS Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.) PMID:23150934

  8. Investigation of HOXA9 promoter methylation as a biomarker to distinguish oral cancer patients at low risk of neck metastasis

    International Nuclear Information System (INIS)

    Uchida, Kenichiro; Veeramachaneni, Ratna; Huey, Bing; Bhattacharya, Aditi; Schmidt, Brian L; Albertson, Donna G

    2014-01-01

    Metastasis to the cervical (neck) lymph nodes is one of the most significant clinical factors responsible for death from oral squamous cell carcinoma (SCC). Therefore, the lymph nodes are frequently removed when the tumor is excised (neck dissection), even though the majority of patients will not benefit from the extra surgery. Two subtypes of oral SCC distinguished by the presence of tumor genomic aberrations +3q, -8p, +8q and/or +20 differ in risk for metastasis – high for the 3q8pq20 subtype, harboring one or more of the aberrations and low for the non-3q8pq20 subtype, lacking these alterations. A prior analysis of the literature suggested genes differentially methylated in the two subtypes. Therefore, the goal of this study was to further investigate the methylation status of candidate biomarkers of the non-3q8pq20 subtype, and evaluate their utility for identifying patients at low risk for metastasis. Methylation status of genes in a cohort of 52 oral SCC patients with at least five year follow up was determined by pyrosequencing. Gene expression levels were determined by quantitative RT-PCR. Growth following re-expression of HOXA9 in cultured oral SCC cells was assessed by proliferation and colony formation assays. A pilot study evaluating methylation levels of HOXA9, MT1A and HOXA11 promoters in DNA from 12 tumors (six each of the 3q8pq20 and non-3q8pq20 subtypes) revealed that only HOXA9 was differentially methylated. Significant differences in methylation levels of HOXA9 were observed amongst the 52 oral SCCs with respect to genomic subtype and nodal status (p = 0.014, and p = 0.024, respectively, Wilcoxon rank sum test). High levels of HOXA9 methylation and low levels of expression in oral SCC cell lines were observed compared to HaCaT, a non-tumorigenic keratinocyte cell line. Re-expression of HOXA9 in the SCC4 oral cancer cell line resulted in diminished proliferation and colony formation. HOXA9 methylation is frequent in oral cancers and levels are

  9. The Design and Operation of Suborbital Low Cost and Low Risk Vehicle to the Edge of Space (SOLVES)

    Science.gov (United States)

    Ridzuan Zakaria, Norul; Nasrun, Nasri; Rashidy Zulkifi, Mohd; Izmir Yamin, Mohd; Othman, Jamaludin; Rafidi Zakaria, Norul

    2013-09-01

    Inclusive in the planning of Spaceport Malaysia are 2 local suborbital vehicles development. One of the vehicles is called SOLVES or Suborbital Low Cost and Low Risk Vehicle to the Edge of Space. The emphasis on the design and operation of SOLVES is green and robotic technology, where both green technology and robotic technology are used to protect the environment and enhance safety. As SOLVES climbs, its center of gravity stabilizes and remains at the bottom as its propellant being used until it depletes, due to the position of the vehicle's passenger cabin and its engines at its lower end. It will reach 80km from sea level generally known as "the edge of space" due to its momentum although its propellant will be depleted at a lower altitude. As the suborbital vehicle descends tail first, its wings automatically extend and rotate at horizontal axes perpendicular to the fuselage. These naturally and passively rotating wings ensure controlled low velocity and stable descend of the vehicle. The passenger cabin also rotates automatically at a steady low speed at the centerline of its fuselage as it descends, caused naturally by the lift force, enabling its passengers a surrounding 360 degrees view. SOLVES is steered automatically to its landing point by an electrical propulsion system with a vectoring nozzle. The electrical propulsion minimizes space and weight and is free of pollution and noise. Its electrical power comes from a battery aided by power generated by the naturally rotating wings. When the vehicle lands, it is in the safest mode as its propellant is depleted and its center of gravity remains at the bottom of its cabin. The cabin, being located at the bottom of the fuselage, enables very convenient, rapid and safe entry and exit of its passengers. SOLVES will be a robotic suborbital vehicle with green technology. The vehicle will carry 4 passengers and each passenger will be trained to land the vehicle manually if the fully automated landing system fails

  10. Reference intervals for hemoglobin and hematocrit in a low-risk pregnancy cohort: implications of racial differences.

    Science.gov (United States)

    Chiossi, Giuseppe; Palomba, Stefano; Costantine, Maged M; Falbo, Angela I; Harirah, Hassan M; Saade, George R; La Sala, Giovanni B

    2018-03-23

    As anemia in pregnancy is associated with adverse perinatal outcomes, we sought to define the mean and the fifth percentile of Hb and Ht using a contemporary multiethnic large cohort of low-risk pregnancies, and assess potential racial differences. We conducted a retrospective cohort study on women who delivered between 1 January 2008 and 31 December 2013 in Reggio Emilia County, Italy. Linear mixed effects models were used to describe changes in mean Hb and Ht, while quantile regression with matrix-design bootstrap defined changes in the fifth percentile of Hb and Ht, controlling for race, maternal age, smoking, and pregnancy number. We analyzed 23,657 hemograms from 7318 pregnancies and 6870 women. Multivariate analysis showed that when compared to Caucasians', African women's mean Hb and Ht were respectively 0.24 (95%CI 0.3-0.17) g/dl and 0.7 (95%CI 0.8-0.5) % lower, while Asian mothers' were 0.11 (95%CI 0.19-0.03) g/dl and 0.3 (95%CI 0.5-0.1) % inferior. Similarly, both African and Asian women had lower fifth Ht percentiles (-1, 95%CI -1.3 to -0.6, and -0.4, 95%CI -0.7 to -0.04) than Caucasians, while African mothers also had lower fifth Hb percentile (0.3, 95%CI 0.5-0.1). The fifth percentile for Hb and Ht were, respectively, 11.3 (95%CI 11-11.5) g/dl and 32.8 (95%CI 32.3-33.4) % in the first trimester, 10.4 (95%CI 10.1-10.6) g/dl and 30.2 (95%CI 29.6-30.8) % in the second trimester, 10.1 (95%CI 9.8-10.3) g/dl and 30.6 (95%CI 30-31.1) % in the third trimester. We provided contemporary references to define anemia in pregnancy, and we confirmed that even in pregnancy, African and Asian women have lower Hb and Ht than Caucasian. Racial and population-specific references may have significant clinical and public health implication for more accurate disease diagnosis and appropriate treatment.

  11. Beta-glucosidase variants and polynucleotides encoding same

    Science.gov (United States)

    Wogulis, Mark; Harris, Paul; Osborn, David

    2017-06-27

    The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.

  12. Word Variant Identification in Old French

    Directory of Open Access Journals (Sweden)

    Peter Willett

    1997-01-01

    Full Text Available Increasing numbers of historical texts are available in machine-readable form, which retain the original spelling, which can be very different from the modern-day equivalents due to the natural evolution of a language, and because the concept of standardisation in spelling is comparatively modern. Among medieval vernacular writers, the same word could be spelled in different ways and the same author (or scribe might even use several alternative spellings in the same passage. Thus, we do not know,a priori, how many variant forms of a particular word there are in such texts, let alone what these variants might be. Searching on the modern equivalent, or even the commonest historical variant, of a particular word may thus fail to retrieve an appreciable number of occurrences unless the searcher already has an extensive knowledge of the language of the documents. Moreover, even specialist scholars may be unaware of some idiosyncratic variants. Here, we consider the use of computer methods to retrieve variant historical spellings.

  13. Evaluation of a Low-risk Mild Traumatic Brain Injury and Intracranial Hemorrhage Emergency Department Observation Protocol.

    Science.gov (United States)

    Yun, Brian J; Borczuk, Pierre; Wang, Lulu; Dorner, Stephen; White, Benjamin A; Raja, Ali S

    2017-11-20

    ] = 0.25-0.82, p = 0.009) in the observation unit. After a stay in the EDOU, 26% (37/143) of patients required an inpatient admission before implementation of the protocol and 13% (20/153) of patients required an inpatient admission after protocol implementation. There was no statistically significant difference in log transformed EDOU length of stay (LOS) between the groups after adjusting for propensity score (p = 0.34). While there was no difference in EDOU LOS, implementing a low-risk mild TBI and ICH protocol in the EDOU may decrease the rate of inpatient admissions from the EDOU. A protocol-driven observation unit may help physicians by standardizing eligibility criteria and by providing guidance on management. As the propensity score method limits our ability to create a straightforward predictive model, a future larger study should validate the results. © 2017 by the Society for Academic Emergency Medicine.

  14. Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic

    DEFF Research Database (Denmark)

    Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y

    2015-01-01

    by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts and thus can be considered pathogenic (c.4987A>T/p.Met1663Leu, c.4988T>A/p.Met1663Lys, c.5072C>T/p.Thr1691Ile, c......Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently...... needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined...

  15. Decision Support and Shared Decision Making About Active Surveillance Versus Active Treatment Among Men Diagnosed with Low-Risk Prostate Cancer: a Pilot Study.

    Science.gov (United States)

    Myers, Ronald E; Leader, Amy E; Censits, Jean Hoffman; Trabulsi, Edouard J; Keith, Scott W; Petrich, Anett M; Quinn, Anna M; Den, Robert B; Hurwitz, Mark D; Lallas, Costas D; Hegarty, Sarah E; Dicker, Adam P; Zeigler-Johnson, Charnita M; Giri, Veda N; Ayaz, Hasan; Gomella, Leonard G

    2018-02-01

    This study aimed to explore the effects of a decision support intervention (DSI) and shared decision making (SDM) on knowledge, perceptions about treatment, and treatment choice among men diagnosed with localized low-risk prostate cancer (PCa). At a multidisciplinary clinic visit, 30 consenting men with localized low-risk PCa completed a baseline survey, had a nurse-mediated online DS session to clarify preference for active surveillance (AS) or active treatment (AT), and met with clinicians for SDM. Participants also completed a follow-up survey at 30 days. We assessed change in treatment knowledge, decisional conflict, and perceptions and identified predictors of AS. At follow-up, participants exhibited increased knowledge (p decision. Perceived support of the decision facilitated patient choice of AS.

  16. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    Directory of Open Access Journals (Sweden)

    Kirtan Nautiyal

    2015-01-01

    Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

  17. Thymic epithelial tumors: Comparison of CT and MR imaging findings of low-risk thymomas, high-risk thymomas, and thymic carcinomas

    International Nuclear Information System (INIS)

    Sadohara, Junko; Fujimoto, Kiminori; Mueller, Nestor L.; Kato, Seiya; Takamori, Shinzo; Ohkuma, Kazuaki; Terasaki, Hiroshi; Hayabuchi, Naofumi

    2006-01-01

    Objective: To assess the CT and magnetic resonance (MR) imaging findings of thymic epithelial tumors classified according to the current World Health Organization (WHO) histologic classification and to determine useful findings in differentiating the main subtypes. Materials and methods: Sixty patients with thymic epithelial tumor who underwent both CT and MR imaging were reviewed retrospectively. All cases were classified according to the 2004 WHO classification. The following findings were assessed in each case on both CT and MRI: size of tumor, contour, perimeter of capsule; homogeneity, presence of septum, hemorrhage, necrotic or cystic component within tumor; presence of mediastinal lymphadenopathy, pleural effusion, and great vessel invasion. These imaging characteristics of 30 low-risk thymomas (4 type A, 12 type AB, and 14 type B1), 18 high-risk thymomas (11 type B2 and seven type B3), and 12 thymic carcinomas on CT and MR imaging were compared using the chi-square test. Comparison between CT and MR findings was performed by using McNemar test. Results: On both CT and MR imaging, thymic carcinomas were more likely to have irregular contours (P < .001), necrotic or cystic component (P < .05), heterogeneous contrast-enhancement (P < .05), lymphadenopathy (P < .0001), and great vessel invasion (P < .001) than low-risk and high-risk thymomas. On MR imaging, the findings of almost complete capsule, septum, and homogenous enhancement were more commonly seen in low-risk thymomas than high-risk thymomas and thymic carcinomas (P < .05). MR imaging was superior to CT in the depiction of capsule, septum, or hemorrhage within tumor (all comparison, P < .05). Conclusion: The presence of irregular contour, necrotic or cystic component, heterogeneous enhancement, lymphadenopathy, and great vessel invasion on CT or MR imaging are strongly suggestive of thymic carcinomas. On MR imaging, the findings of contour, capsule, septum, and homogenous enhancement are helpful in

  18. Comparative effectiveness of laparoscopic versus open prostatectomy for men with low-risk prostate cancer: a matched case-control study

    Science.gov (United States)

    Patel, Amil; Kim, Sinae; Kim, Isaac Yi; Goyal, Sharad

    2017-01-01

    Background: Little data exist on effect of undergoing laparoscopic prostatectomy(LP) versus open prostatectomy(OP) upon 30-day mortality rates among low-risk prostate cancer patients. Materials and methods: Using the National Cancer Database, we identified men (2004 to 2013) with biopsy-proven, low-risk prostate cancer who met the eligibility criteria: N0, M0, T-stage≤2A, PSA≤10 ng/mL, and Gleason score=6. We utilized a 1:N matched case-control study, with cases and controls matched by race, insurance status, Charlson-Deyo comorbidity score, surgical margin status, and facility type to investigate the short-term comparative effectiveness of LP versus OP. Results: Among the 448,773 patients in the National Cancer Database with low-risk prostate cancer, 116,359 patients met the above inclusion criteria. The target group was restricted to patients who received LP or OP, thus, leaving 44,720 patients for the study. The use of LP (compared with OP) was associated with patients with privately insured patients, treatment at an academic/research centers, high-volume hospitals, and white race (all Popen) was estimated at 0.31 (95% confidence interval, 0.135–0.701; P<0.05). Thus, the risk of death within 30 days was 69% lower with LP compared with OP. Conclusions: We found that the 30-day mortality rate among low-risk prostate cancer patients is significantly lower among patients who received LP when compared with OP, with various clinicopathologic parameters associated with its preferential use. PMID:29177226

  19. Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women.

    Science.gov (United States)

    Robison, Katina; Cronin, Beth; Bregar, Amy; Luis, Christine; DiSilvestro, Paul; Schechter, Steven; Pisharodi, Latha; Raker, Christina; Clark, Melissa

    2015-12-01

    To compare the prevalence of abnormal anal cytology and high-risk human papillomavirus (HPV) among women with a history of HPV-related genital neoplasia with women without a history of HPV-related genital neoplasia. A cross-sectional cohort study was performed from December 2012 to February 2014. Women were recruited from outpatient clinics at an academic medical center. Women with a history of high-grade cervical, vulvar, or vaginal cytology, dysplasia, or cancer were considered the high-risk group. Women with no history of high-grade anogenital dysplasia or cancer were considered the low-risk group. Human immunodeficiency virus-positive women were excluded. Anal cytology and HPV genotyping were performed. Women with abnormal anal cytology were referred for high-resolution anoscopy. There were 190 women in the high-risk group and 83 in the low-risk group. The high-risk group was slightly older: 57 years compared with 47 years (P=.045); 21.7% of low-risk women had abnormal anal cytology compared with 41.2% of high-risk women (P=.006). High-risk HPV was detected in the anal canal of 1.2% of the low-risk group compared with 20.8% of the high-risk group (PHuman immunodeficiency virus-negative women with a history of lower genital tract neoplasia are more likely to have positive anal cytology, anal high-risk HPV, and anal intraepithelial neoplasia. Anal cancer screening should be considered for these high-risk women. II.

  20. The genesis of breast cancer is a two-step phenomenon. II. Dissociation of two biomarkers in cancer patients from a low risk area of Japan.

    Science.gov (United States)

    Kodama, M; Kodama, T; Murakami, M; Kobayashi, S; Akita, T; Nakamura, Y

    1992-01-01

    The association of dual steroidal disorders with breast cancer, as proposed on the basis of a case-control study in a high risk area of Japan, was tested for its validity in breast cancer patients from a low risk area of Japan. A state of glucocorticoid excess, the first hormonal trait of a breast cancer patient, was assessed using a urinary steroid parameter (a reduction of the androsterone to tetrahydrocortisol ratio by definition), and/or using a physical parameter (an elevation of the waist to hip circumference ratio by definition). Inclination to ovulation failure, the second hormonal trait, was tested using another urinary steroid parameter (a specified disorder of progestin metabolism by definition), and/or a demographic parameter (a reduction in the number of live births by definition). Results obtained are as follows: 1) premenopausal breast cancer patients from a low risk area were found to have the second trait but not the first trait, as tested using 2 parameters for each trait. 2) Postmenopausal cancer patients from a low risk area as well as pre- and post-menopausal cancer patients from a high risk area had both the 2 hormonal traits. 3) There was no discrepancy of results between any 2 test systems with the identification of 2 hormonal traits in 4 cancer patient groups. The significance of the dissociation of 2 hormonal traits, as observed in premenopausal cancer patients from a low risk area, is discussed in favor of the two-step carcinogenesis theory. Possible interaction of heredity and environment in the genesis of breast cancer is also taken into consideration.

  1. Mode of birth and medical interventions among women at low risk of complications: A cross-national comparison of birth settings in England and the Netherlands.

    Directory of Open Access Journals (Sweden)

    Ank de Jonge

    Full Text Available To compare mode of birth and medical interventions between broadly equivalent birth settings in England and the Netherlands.Data were combined from the Birthplace study in England (from April 2008 to April 2010 and the National Perinatal Register in the Netherlands (2009. Low risk women in England planning birth at home (16,470 or in freestanding midwifery units (11,133 were compared with Dutch women with planned home births (40,468. Low risk English women with births planned in alongside midwifery units (16,418 or obstetric units (19,096 were compared with Dutch women with planned midwife-led hospital births (37,887.CS rates varied across planned births settings from 6.5% to 15.5% among nulliparous and 0.6% to 5.1% among multiparous women. CS rates were higher among low risk nulliparous and multiparous English women planning obstetric unit births compared to Dutch women planning midwife-led hospital births (adjusted (adj OR 1.89 (95% CI 1.64 to 2.18 and 3.66 (2.90 to 4.63 respectively. Instrumental vaginal birth rates varied from 10.7% to 22.5% for nulliparous and from 0.9% to 5.7% for multiparous women. Rates were lower in the English comparison groups apart from planned births in obstetric units. Transfer, augmentation and episiotomy rates were much lower in England compared to the Netherlands for all midwife-led groups. In most comparisons, epidural rates were higher among English groups.When considering maternal outcomes, findings confirm advantages of giving birth in midwife-led settings for low risk women. Further research is needed into strategies to decrease rates of medical intervention in obstetric units in England and to reduce rates of avoidable transfer, episiotomy and augmentation of labour in the Netherlands.

  2. Early Discharge in Low-Risk Patients Hospitalized for Acute Coronary Syndromes: Feasibility, Safety and Reasons for Prolonged Length of Stay.

    Directory of Open Access Journals (Sweden)

    Marie-Eva Laurencet

    Full Text Available Length of hospital stay (LHS is an indicator of clinical effectiveness. Early hospital discharge (≤72 hours is recommended in patients with acute coronary syndromes (ACS at low risk of complications, but reasons for prolonged LHS poorly reported.We collected data of ACS patients hospitalized at the Geneva University Hospitals from 1st July 2013 to 30th June 2015 and used the Zwolle index score to identify patients at low risk (≤ 3 points. We assessed the proportion of eligible patients who were successfully discharged within 72 hours and the reasons for prolonged LHS. Outcomes were defined as adherence to recommended therapies, major adverse events at 30 days and patients' satisfaction using a Likert-scale patient-reported questionnaire.Among 370 patients with ACS, 255 (68.9% were at low-risk of complications but only 128 (50.2%were eligible for early discharge, because of other clinical reasons for prolonged LHS (e.g. staged coronary revascularization, cardiac monitoring in 127 patients (49.8%. Of the latter, only 45 (35.2% benefitted from an early discharge. Reasons for delay in discharge in the remaining 83 patients (51.2% were mainly due to delays in additional investigations, titration of medical therapy, admission or discharge during weekends. In the early discharge group, at 30 days, only one patient (2.2% had an adverse event (minor bleeding, 97% of patients were satisfied by the medical care.Early discharge was successfully achieved in one third of eligible ACS patients at low risk of complications and appeared sufficiently safe while being overall appreciated by the patients.

  3. Early Discharge in Low-Risk Patients Hospitalized for Acute Coronary Syndromes: Feasibility, Safety and Reasons for Prolonged Length of Stay.

    Science.gov (United States)

    Laurencet, Marie-Eva; Girardin, François; Rigamonti, Fabio; Bevand, Anne; Meyer, Philippe; Carballo, David; Roffi, Marco; Noble, Stéphane; Mach, François; Gencer, Baris

    2016-01-01

    Length of hospital stay (LHS) is an indicator of clinical effectiveness. Early hospital discharge (≤72 hours) is recommended in patients with acute coronary syndromes (ACS) at low risk of complications, but reasons for prolonged LHS poorly reported. We collected data of ACS patients hospitalized at the Geneva University Hospitals from 1st July 2013 to 30th June 2015 and used the Zwolle index score to identify patients at low risk (≤ 3 points). We assessed the proportion of eligible patients who were successfully discharged within 72 hours and the reasons for prolonged LHS. Outcomes were defined as adherence to recommended therapies, major adverse events at 30 days and patients' satisfaction using a Likert-scale patient-reported questionnaire. Among 370 patients with ACS, 255 (68.9%) were at low-risk of complications but only 128 (50.2%)were eligible for early discharge, because of other clinical reasons for prolonged LHS (e.g. staged coronary revascularization, cardiac monitoring) in 127 patients (49.8%). Of the latter, only 45 (35.2%) benefitted from an early discharge. Reasons for delay in discharge in the remaining 83 patients (51.2%) were mainly due to delays in additional investigations, titration of medical therapy, admission or discharge during weekends. In the early discharge group, at 30 days, only one patient (2.2%) had an adverse event (minor bleeding), 97% of patients were satisfied by the medical care. Early discharge was successfully achieved in one third of eligible ACS patients at low risk of complications and appeared sufficiently safe while being overall appreciated by the patients.

  4. Systematic review with meta-analysis: the incidence of advanced neoplasia after polypectomy in patients with and without low-risk adenomas.

    Science.gov (United States)

    Hassan, C; Gimeno-García, A; Kalager, M; Spada, C; Zullo, A; Costamagna, G; Senore, C; Rex, D K; Quintero, E

    2014-05-01

    Patients with one to two tubular adenomas advanced neoplasia as those with no neoplasia at baseline colonoscopy. To compare incidence of metachronous advanced neoplasia between patients in the low-risk adenoma group and those without neoplasia at index colonoscopy. Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1992-2013. Studies comparing the incidence of post-polypectomy advanced neoplasia (adenomas ≥10 mm/high-grade dysplasia/villous or cancer) between the low-risk group and patients without colorectal neoplasia at the first colonoscopy were included. Detection rates for advanced neoplasia at endoscopic surveillance were extracted. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was produced based on random-effect models. Inter-study heterogeneity was assessed using the I(2) statistic. Seven studies provided data on 11 387 patients. Mean surveillance periods ranged between 2 and 5 years. Altogether, 267 patients with post-polypectomy advanced neoplasia were detected in the two groups. The incidence of advanced neoplasia was 1.6% (119/7308) in those without neoplasia and 3.6% (148/4079) in those with low-risk adenoma, respectively, corresponding to a relative risk of 1.8 (95% CI: 1.3-2.6). Inter-study heterogeneity was only moderate (I(2) : 37%). No publication bias was present. Patients with low-risk adenomas at baseline had a higher risk of metachronous advanced neoplasia than the group with no adenomas at baseline, though the absolute risk was low in both groups. © 2014 John Wiley & Sons Ltd.

  5. Pathological and Biochemical Outcomes among African-American and Caucasian Men with Low Risk Prostate Cancer in the SEARCH Database: Implications for Active Surveillance Candidacy.

    Science.gov (United States)

    Leapman, Michael S; Freedland, Stephen J; Aronson, William J; Kane, Christopher J; Terris, Martha K; Walker, Kelly; Amling, Christopher L; Carroll, Peter R; Cooperberg, Matthew R

    2016-11-01

    Racial disparities in the incidence and risk profile of prostate cancer at diagnosis among African-American men are well reported. However, it remains unclear whether African-American race is independently associated with adverse outcomes in men with clinical low risk disease. We retrospectively analyzed the records of 895 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database in whom clinical low risk prostate cancer was treated with radical prostatectomy. Associations of African-American and Caucasian race with pathological biochemical recurrence outcomes were examined using chi-square, logistic regression, log rank and Cox proportional hazards analyses. We identified 355 African-American and 540 Caucasian men with low risk tumors in the SEARCH cohort who were followed a median of 6.3 years. Following adjustment for relevant covariates African-American race was not significantly associated with pathological upgrading (OR 1.33, p = 0.12), major upgrading (OR 0.58, p = 0.10), up-staging (OR 1.09, p = 0.73) or positive surgical margins (OR 1.04, p = 0.81). Five-year recurrence-free survival rates were 73.4% in African-American men and 78.4% in Caucasian men (log rank p = 0.18). In a Cox proportional hazards analysis model African-American race was not significantly associated with biochemical recurrence (HR 1.11, p = 0.52). In a cohort of patients at clinical low risk who were treated with prostatectomy in an equal access health system with a high representation of African-American men we observed no significant differences in the rates of pathological upgrading, up-staging or biochemical recurrence. These data support continued use of active surveillance in African-American men. Upgrading and up-staging remain concerning possibilities for all men regardless of race. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Management of low-risk early-stage cervical cancer: Should conization, simple trachelectomy, or simple hysterectomy replace radical surgery as the new standard of care?

    Science.gov (United States)

    Ramirez, Pedro T.; Pareja, Rene; Rendón, Gabriel J.; Millan, Carlos; Frumovitz, Michael; Schmeler, Kathleen M.

    2014-01-01

    The standard treatment for women with early-stage cervical cancer (IA2-IB1) remains radical hysterectomy with pelvic lymphadenectomy. In select patients interested in future fertility, the option of radical trachelectomy with pelvic lymphadenectomy is also considered a viable option. The possibility of less radical surgery may be appropriate not only for patients desiring to preserve fertility but also for all patients with low-risk early-stage cervical cancer. Recently, a number of studies have explored less radical surgical options for early-stage cervical cancer, including simple hysterectomy, simple trachelectomy, and cervical conization with or without sentinel lymph node biopsy and pelvic lymph node dissection. Such options may be available for patients with low-risk early-stage cervical cancer. Criteria that define this low-risk group include: squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma, tumor size <2 cm, stromal invasion <10mm, and no lymph-vascular space invasion. In this report, we provide a review of the existing literature on the conservative management of cervical cancer and describe ongoing multi-institutional trials evaluating the role of conservative surgery in selected patients with early-stage cervical cancer. PMID:24041877

  7. KIT Mutation and Loss of 14q May Be Sufficient for the Development of Clinically Symptomatic Very Low-Risk GIST.

    Directory of Open Access Journals (Sweden)

    Olaf Karl Klinke

    Full Text Available The aim of this study was to determine the minimal set of genetic alterations required for the development of a very low risk clinically symptomatic gastro-intestinal stromal tumour within the stomach wall. We studied the genome of a very low-risk gastric gastro-intestinal stromal tumour by whole-genome sequencing, comparative genomic hybridisation and methylation profiling. The studied tumour harboured two typical genomic lesions: loss of the long arm of chromosome 14 and an activating mutation in exon 11 of KIT. Besides these genetic lesions, only two point mutations that may affect tumour progression were identified: A frame-shift deletion in RNF146 and a missense mutation in a zinc finger of ZNF407. Whilst the frameshift deletion in RNF146 seemed to be restricted to this particular tumour, a similar yet germline mutation in ZNF407 was found in a panel of 52 gastro-intestinal stromal tumours from different anatomical sites and different categories. Germline polymorphisms in the mitotic checkpoint proteins Aurora kinase A and BUB1 kinase B may have furthered tumour growth. The epigenetic profile of the tumour matches that of other KIT-mutant tumours. We have identified mutations in three genes and loss of the long arm of chromosome 14 as the so far minimal set of genetic abnormalities sufficient for the development of a very low risk clinically symptomatic gastric stromal tumour.

  8. Evaluating the use of antibiotic prophylaxis during open reduction and internal fixation surgery in patients at low risk of surgical site infection.

    Science.gov (United States)

    Xu, Sheng-Gen; Mao, Zhao-Guang; Liu, Bin-Sheng; Zhu, Hui-Hua; Pan, Hui-Lin

    2015-02-01

    Widespread overuse and inappropriate use of antibiotics contribute to increasingly antibiotic-resistant pathogens and higher health care costs. It is not clear whether routine antibiotic prophylaxis can reduce the rate of surgical site infection (SSI) in low-risk patients undergoing orthopaedic surgery. We designed a simple scorecard to grade SSI risk factors and determined whether routine antibiotic prophylaxis affects SSI occurrence during open reduction and internal fixation (ORIF) orthopaedic surgeries in trauma patients at low risk of developing SSI. The SSI risk scorecard (possible total points ranged from 5 to 25) was designed to take into account a patient's general health status, the primary cause of fractures, surgical site tissue condition or wound class, types of devices implanted, and surgical duration. Patients with a low SSI risk score (≤8 points) who were undergoing clean ORIF surgery were divided into control (routine antibiotic treatment, cefuroxime) and evaluation (no antibiotic treatment) groups and followed up for 13-17 months after surgery. The infection rate was much higher in patients with high SSI risk scores (≥9 points) than in patients with low risk scores assigned to the control group (10.7% vs. 2.2%, Prisk score. Implementation of this scoring system could guide the rational use of perioperative antibiotics and ultimately reduce antibiotic resistance, health care costs, and adverse reactions to antibiotics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Is {sup 131}I ablation necessary for patients with low-risk papillary thyroid carcinoma and slightly elevated stimulated thyroglobulin after thyroidectomy?

    Energy Technology Data Exchange (ETDEWEB)

    Rosario, Pedro Weslley; Mourao, Gabriela Franco, E-mail: pedrowsrosario@gmail.com [Santa Casa de Belo Horizonte, MG (Brazil). Instituto de Ensino e Pesquisa

    2016-02-15

    Objective: This prospective study evaluated the recurrence rate in low-risk patients with papillary thyroid cancer (PTC) who presented slightly elevated thyroglobulin (Tg) after thyroidectomy and who did not undergo ablation with {sup 131}I. Subjects and methods: The study included 53 low-risk patients (non aggressive histology; pT1b-3, cN0pNx, M0) with slightly elevated Tg after thyroidectomy (> 1 ng/mL, but ≤ 5 ng/mL after levothyroxine withdrawal or ≤ 2 ng/mL after recombinant human TSH). Results: The time of follow-up ranged from 36 to 96 months. Lymph node metastases were detected in only one patient (1.9%). Fifty-two patients continued to present negative neck ultrasound. None of these patients without apparent disease presented an increase in Tg. Conclusions: Low-risk patients with PTC who present slightly elevated Tg after thyroidectomy do not require ablation with {sup 131}I. (author)

  10. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  11. Hemoglobin Variants: Biochemical Properties and Clinical Correlates

    Science.gov (United States)

    Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

    2013-01-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

  12. [Clinico-pathogenetic variants of chronic gastritis].

    Science.gov (United States)

    Chernin, V V; Dzhulaĭ, G S

    2004-01-01

    To evaluate specific features of the course of chronic gastritis (CG), morphofunctional condition of gastric mucosa, vegetative regulation, adrenergic and cholinergic shifts, histamine metabolism and effects of exogenic and endogenic risk factors in CG patients; to study clinicopathogenetic variants of CG. A total of 311 CG patients aged from 16 to 72 years were studied. They were divided into three groups by their gastric mucosa condition. The control group consisted of 30 healthy donors. The following parameters were studied: visual and histological condition of gastric mucosa, total acidity, the levels of free hydrochloric acid, pepsin, bioelectric gastric activity, general autonomic tonicity, cholinesterase activity. Three clinicopathogenetic variants of the disease have been identified. Variant 1 was characterized by a recurrent course, subjective manifestation of the disease only in exacerbation, surface (primarily antral) mucosal affection, normal or enhanced secretory and motor functions of the stomach, adequate reaction of acid production to caffeine and histamine stimulation, parasympathicotonia, absolute hyperhistaminemia, relative hypoacetylcholinemia, subnormal urinary excretion of adrenalin. Variant 2 manifested with rare recurrences, longer and more severe exacerbations, frequent spontaneous and provoked aggravations, moderate focal atrophy of the mucosa, secretory insufficiency with adequate reaction to histamine and minor to caffeine stimuli, hypomotor gastric dyskinesia, vegetative eutonia, normohistaminemia, absolute hypoacetylcholinemia, subnormal urinary excretion of noradrenaline. Variant 3 runs without definite remissions and exacerbations, with continuous abdominal pain and dyspepsia, frequent spontaneous aggravations, marked extended mucosal atrophy with secretory insufficiency up to achlorhydria, no stimulation of acid production in response to caffeine and histamine, gastric hypomotility, sympathicotonia, absolute hypohistaminemia

  13. BRCA1 and BRCA2 missense variants of high and low clinical significance influence lymphoblastoid cell line post-irradiation gene expression.

    Directory of Open Access Journals (Sweden)

    Nic Waddell

    2008-05-01

    Full Text Available The functional consequences of missense variants in disease genes are difficult to predict. We assessed if gene expression profiles could distinguish between BRCA1 or BRCA2 pathogenic truncating and missense mutation carriers and familial breast cancer cases whose disease was not attributable to BRCA1 or BRCA2 mutations (BRCAX cases. 72 cell lines from affected women in high-risk breast ovarian families were assayed after exposure to ionising irradiation, including 23 BRCA1 carriers, 22 BRCA2 carriers, and 27 BRCAX individuals. A subset of 10 BRCAX individuals carried rare BRCA1/2 sequence variants considered to be of low clinical significance (LCS. BRCA1 and BRCA2 mutation carriers had similar expression profiles, with some subclustering of missense mutation carriers. The majority of BRCAX individuals formed a distinct cluster, but BRCAX individuals with LCS variants had expression profiles similar to BRCA1/2 mutation carriers. Gaussian Process Classifier predicted BRCA1, BRCA2 and BRCAX status, with a maximum of 62% accuracy, and prediction accuracy decreased with inclusion of BRCAX samples carrying an LCS variant, and inclusion of pathogenic missense carriers. Similarly, prediction of mutation status with gene lists derived using Support Vector Machines was good for BRCAX samples without an LCS variant (82-94%, poor for BRCAX with an LCS (40-50%, and improved for pathogenic BRCA1/2 mutation carriers when the gene list used for prediction was appropriate to mutation effect being tested (71-100%. This study indicates that mutation effect, and presence of rare variants possibly associated with a low risk of cancer, must be considered in the development of array-based assays of variant pathogenicity.

  14. Normal variants of skin in neonates

    Directory of Open Access Journals (Sweden)

    Kulkarni M

    1996-01-01

    Full Text Available 2221 consecutive live births taking place between March 1994 and February 1995 were evaluated for a minimum period of 5 days to note for the occurrence of various normal anatomical variants specially those of skin. Birth weight, gestational age, maternal age, socio-economic status and consanguinity were carefully recorded in all the cases. Mongolian spots (72%, Epstein pearls (43.8%, Milia (26.2% and Erythema toxicum (25.2%, were the common dermatological variants noted. Maturity of the babies and possibly genetic factors (consanguinity are important factors in their causation as ordered in our study.

  15. The curation of genetic variants: difficulties and possible solutions.

    Science.gov (United States)

    Pandey, Kapil Raj; Maden, Narendra; Poudel, Barsha; Pradhananga, Sailendra; Sharma, Amit Kumar

    2012-12-01

    The curation of genetic variants from biomedical articles is required for various clinical and research purposes. Nowadays, establishment of variant databases that include overall information about variants is becoming quite popular. These databases have immense utility, serving as a user-friendly information storehouse of variants for information seekers. While manual curation is the gold standard method for curation of variants, it can turn out to be time-consuming on a large scale thus necessitating the need for automation. Curation of variants described in biomedical literature may not be straightforward mainly due to various nomenclature and expression issues. Though current trends in paper writing on variants is inclined to the standard nomenclature such that variants can easily be retrieved, we have a massive store of variants in the literature that are present as non-standard names and the online search engines that are predominantly used may not be capable of finding them. For effective curation of variants, knowledge about the overall process of curation, nature and types of difficulties in curation, and ways to tackle the difficulties during the task are crucial. Only by effective curation, can variants be correctly interpreted. This paper presents the process and difficulties of curation of genetic variants with possible solutions and suggestions from our work experience in the field including literature support. The paper also highlights aspects of interpretation of genetic variants and the importance of writing papers on variants following standard and retrievable methods. Copyright © 2012. Published by Elsevier Ltd.

  16. Magnetic resonance angiography: infrequent anatomic variants

    International Nuclear Information System (INIS)

    Trejo, Mariano; Meli, Francisco; Lambre, Hector; Blessing, Ricardo; Gigy Traynor, Ignacio; Miguez, Victor

    2002-01-01

    We studied through RM angiography (3D TOF) with high magnetic field equipment (1.5 T) different infrequent intracerebral vascular anatomic variants. For their detection we emphasise the value of post-processed images obtained after conventional angiographic sequences. These post-processed images should be included in routine protocols for evaluation of the intracerebral vascular structures. (author)

  17. Report of a rare anatomic variant

    DEFF Research Database (Denmark)

    De Brucker, Y; Ilsen, B; Muylaert, C

    2015-01-01

    We report the CT findings in a case of partial anomalous pulmonary venous return (PAPVR) from the left upper lobe in an adult. PAPVR is an anatomic variant in which one to three pulmonary veins drain into the right atrium or its tributaries, rather than into the left atrium. This results in a left...

  18. Analysis of the energy development variants

    International Nuclear Information System (INIS)

    Tsvetanov, P.

    1990-01-01

    Analysis of the variants of energy development is made as the third stage of a procedure of energy-economy interrelations dynamics study, the other two stages being the scenarios description and the formulation of the variants. This stage includes a research on the dimensions and the dynamics of the resources demands, the general features and the trends of the national energy development. There is a presentation of a comparative analysis of the variants in terms of economic indices and energy values, computed by the model IMPACT-B. A resource evaluation of the development variants is given in terms of investments, requirements (direct, indirect and total) and limited national resources demands of the energy system. The trends of the national energy development discussed are: trends characterizing the changes in the structure of the energy consumption, resulting from changes in the economy; trends of the energy system impact on the productivity of labor; general trends of the proportionality in the industrial, the household and services sector development. 16 refs., 16 figs., 4 tabs. (R.Ts.)

  19. Cellobiohydrolase I gene and improved variants

    Science.gov (United States)

    Adney, William S [Golden, CO; Decker, Stephen R [Berthoud, CO; Mc Carter, Suzanne [San Carlos, CA; Baker, John O [Golden, CO; Nieves, Raphael [Lakewood, CO; Himmel, Michael E [Littleton, CO; Vinzant, Todd B [Golden, CO

    2008-05-20

    The disclosure provides a method for preparing an active exoglucanase in a heterologous host of eukaryotic origin. The method includes mutagenesis to reduce glycosylation of the exoglucanase when expressed in a heterologous host. It is further disclosed a method to produce variant cellobiohydrolase that is stable at high temperature through mutagenesis.

  20. XVCL: XML-based Variant Configuration Language

    DEFF Research Database (Denmark)

    Jarzabek, Stan; Basset, Paul; Zhang, Hongyu

    2003-01-01

    XVCL (XML-based Variant Configuration Language) is a meta-programming technique and tool that provides effective reuse mechanisms. XVCL is an open source software developed at the National University of Singapore. Being a modern and versatile version of Bassett's frames, a technology that has...

  1. Glucose 6-phosphate dehydrogenase variants in Japan.

    Science.gov (United States)

    Miwa, S

    1980-01-01

    Fifty-four cases of glucose 6-phosphate dehydrogenase (G6PD) deficiency have so far been reported in Japan. Among them, 21 G6PD variants have been characterized. Nineteen out of the 21 variants were characterized in our laboratory and G6PD Heian and "Kyoto" by others. G6PD Tokyo, Tokushima, Ogikubo, Kurume, Fukushima, Yokohama, Yamaguchi, Wakayama, Akita, Heian and "Kyoto" were classified as Class 1, because all these cases showed chronic hemolytic anemia and severe enzyme deficiency. All these variants showed thermal instability. G6PD Mediterranean-like, Ogori, Gifu and Fukuoka were classified as Class 2, whereas G6PD Hofu, B(-) Chinese, Ube, Konan, Kamiube and Kiwa belonged to Class 3. All the 6 Class 3 variants were found as the results of the screening tests. The incidence of the deficiency in Japanese seems to be 0.1-0.5% but that of the cases which may slow drug-induced hemolysis would be much less. G6PD Ube and Konan appear to be relatively common in Japan.

  2. Genetic variants influencing phenotypic variance heterogeneity.

    Science.gov (United States)

    Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa

    2018-03-01

    Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.

  3. Genetic variants associated with lung function

    DEFF Research Database (Denmark)

    Thyagarajan, Bharat; Wojczynski, Mary; Minster, Ryan L

    2014-01-01

    with exceptional longevity have not been identified. METHOD: We conducted a genome wide association study (GWAS) to identify novel genetic variants associated with lung function in the Long Life Family Study (LLFS) (n = 3,899). Replication was performed using data from the CHARGE/SpiroMeta consortia...

  4. Influenza A (H3N2) Variant Virus

    Science.gov (United States)

    ... Swine Variant Pandemic Other Influenza A (H3N2) Variant Virus Language: English (US) Español Recommend on Facebook Tweet Share Compartir Influenza viruses that normally circulate in pigs are called “variant” ...

  5. Treatment of spelling variants in Setswana monolingual dictionaries

    African Journals Online (AJOL)

    user

    . ..... Table 8: Variants of Names of persons and places. Setswana variants. English. Aforika, Aferika. Africa. Baebele, Babele, Beibele. Bible. Ennyelane, Engelane ..... MWEs. As in variation amongst individual words, the MWEs such as idioms.

  6. Gateway Effects: Why the Cited Evidence Does Not Support Their Existence for Low-Risk Tobacco Products (and What Evidence Would

    Directory of Open Access Journals (Sweden)

    Carl V. Phillips

    2015-05-01

    Full Text Available It is often claimed that low-risk drugs still create harm because of “gateway effects”, in which they cause the use of a high-risk alternative. Such claims are popular among opponents of tobacco harm reduction, claiming that low-risk tobacco products (e.g., e-cigarettes, smokeless tobacco cause people to start smoking, sometimes backed by empirical studies that ostensibly support the claim. However, these studies consistently ignore the obvious alternative causal pathways, particularly that observed associations might represent causation in the opposite direction (smoking causes people to seek low-risk alternatives or confounding (the same individual characteristics increase the chance of using any tobacco product. Due to these complications, any useful analysis must deal with simultaneity and confounding by common cause. In practice, existing analyses seem almost as if they were designed to provide teaching examples about drawing simplistic and unsupported causal conclusions from observed associations. The present analysis examines what evidence and research strategies would be needed to empirically detect such a gateway effect, if there were one, explaining key methodological concepts including causation and confounding, examining the logic of the claim, identifying potentially useful data, and debunking common fallacies on both sides of the argument, as well as presenting an extended example of proper empirical testing. The analysis demonstrates that none of the empirical studies to date that are purported to show a gateway effect from tobacco harm reduction products actually does so. The observations and approaches can be generalized to other cases where observed association of individual characteristics in cross-sectional data could result from any of several causal relationships.

  7. Written Informed Consent for Computed Tomography of the Abdomen/Pelvis is Associated with Decreased CT Utilization in Low-Risk Emergency Department Patients

    Directory of Open Access Journals (Sweden)

    Lisa H. Merck

    2015-12-01

    Full Text Available Introduction: The increasing rate of patient exposure to radiation from computerized tomography (CT raises questions about appropriateness of utilization. There is no current standard to employ informed consent for CT (ICCT. Our study assessed the relationship between informed consent and CT utilization in emergency department (ED patients. Methods: An observational multiphase before-after cohort study was completed from 4/2010-5/2011. We assessed CT utilization before and after (Time I/ Time II the implementation of an informed consent protocol. Adult patients were included if they presented with symptoms of abdominal/pelvic pathology or completed ED CT. We excluded patients with pregnancy, trauma, or altered mental status. Data on history, exam, diagnostics, and disposition were collected via standard abstraction tool. We generated a multivariate logistic model via stepwise regression, to assess CT utilization across risk groups. Logistic models, stratified by risk, were generated to include study phase and a propensity score that controlled for potential confounders of CT utilization. Results: 7,684 patients met inclusion criteria. In PHASE 2, there was a 24% (95% CI [10-36%] reduction in CT utilization in the low-risk patient group (p<0.002. ICCT did not affect CT utilization in the high-risk group (p=0.16. In low-risk patients, the propensity score was significant (p<0.001. There were no adverse events reported during the study period. Conclusion: The implementation of ICCT was associated with reduced CT utilization in low-risk ED patients. ICCT has the potential to increase informed, shared decision making with patients, as well as to reduce the risks and cost associated with CT.

  8. Comparison of seed brachytherapy or external beam radiotherapy (70 Gy or 74 Gy) in 919 low-risk prostate cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Goldner, G.; Poetter, R.; Schmid, M.P.; Kirisits, C. [University Hospital of Vienna (Austria). Dept. of Radiotherapy and Radiobiology; Battermann, J.J.; Sljivic, S.; Vulpen, M. van [University Medical Center Utrecht (Netherlands). Dept. of Radiation Oncology

    2012-04-15

    The aim of this analysis was to compare the biochemical no evidence of disease (bNED) rates in low-risk prostate cancer patients treated at two centers of excellence using different approaches: seed brachytherapy (BT) and external beam radiotherapy (EBRT). Materials and methods: A total of 919 low-risk prostate cancer patients, treated from 1998-2008, were identified in the two databases. In Utrecht, 667 patients received I-125 BT applying a dose of 144 Gy. In Vienna, 252 patients were treated with EBRT, applying a local dose of 70 Gy in 82 patients and 74 Gy in 170 patients. bNED rates (Phoenix definition) were assessed. Results: The median follow-up was 46 months (range 1-148 months). The 5-year actuarial bNED rates were 94% for BT patients and 88% for EBRT patients (p = 0.002) - 84% for patients receiving 70 Gy and 91% for patients receiving 74 Gy, respectively. In the univariate analysis, patients receiving 70 Gy showed significantly worse outcome compared to BT (p = 0.001) and a difference close to significance compared to 74 Gy (p = 0.06). In the multivariate analysis including tumor stage, Gleason score, initial PSA, hormonal therapy, and dose, patients receiving 70 Gy EBRT showed significantly worse bNED rates compared to BT patients. Conclusion: Low-risk prostate cancer patients receiving 74 Gy by EBRT show comparable biochemical control rates to patients receiving seed brachytherapy, whereas patients receiving 70 Gy show significantly worse outcome. (orig.)

  9. No survival difference after successful {sup 131}I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Verburg, Frederik Anton [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Stokkel, Marcel P.M.; Verkooijen, Robbert B.T. [Leiden University Medical Center, Department of Radiology, Division of Nuclear Medicine, Leiden (Netherlands); Dueren, Christian; Reiners, Christoph [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Maeder, Uwe [University of Wuerzburg, Comprehensive Cancer Center, Wuerzburg (Germany); Isselt, Johannes W. van [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Marlowe, Robert J. [Spencer-Fontayne Corporation, Jersey City, NJ (United States); Smit, Johannes W. [Leiden University Medical Center, Department of Endocrinology, Leiden (Netherlands); Luster, Markus [University of Ulm, Department of Nuclear Medicine, Ulm (Germany)

    2010-02-15

    To compare disease-specific survival and recurrence-free survival (RFS) after successful {sup 131}I ablation in patients with differentiated thyroid carcinoma (DTC) between those defined before ablation as low-risk and those defined as high-risk according to the European Thyroid Association 2006 consensus statement. Retrospective data from three university hospitals were pooled. Of 2009 consecutive patients receiving ablation, 509 were identified as successfully ablated based on both undetectable stimulated serum thyroglobulin in the absence of antithyroglobulin antibodies and a negative diagnostic whole-body scan in a follow-up examination conducted 8.1{+-}4.6 months after ablation. Of these 509 patients, 169 were defined as high-risk. After a mean follow-up of 81{+-}64 months (range 4-306 months), only three patients had died of DTC, rendering assessment of disease-specific survival differences impossible. Of the 509 patients, 12 (2.4%) developed a recurrence a mean 35 months (range 12-59 months) after ablation. RFS for the duration of follow-up was 96.6% according to the Kaplan-Meier method. RFS did not differ between high-risk and low-risk patients (p=0.68). RFS differed slightly but significantly between those with papillary and those with follicular thyroid carcinoma (p=0.03) and between those aged {<=}45 years those aged >45 years at diagnosis (p=0.018). After (near) total thyroidectomy and successful {sup 131}I ablation, RFS does not differ between patients classified as high-risk and those classified as low-risk based on TNM stage at diagnosis. Consequently, the follow-up protocol should be determined on the basis of the result of initial treatment rather than on the initial tumour classification. (orig.)

  10. Outpatient thyroid remnant ablation using repeated low 131-iodine activities (740 MBq/20 mCix2) in patients with low-risk differentiated thyroid cancer.

    Science.gov (United States)

    Clerc, Jérôme; Bienvenu-Perrard, Marie; de Malleray, Caroline Pichard; Dagousset, Françoise; Delbot, Thierry; Dreyfuss, Marc; Groussin, Lionel; Marlowe, Robert J; Leger, Françoise Aubène; Chevalier, Alain

    2012-03-01

    In low-risk differentiated thyroid cancer (DTC), postoperative (131)I remnant ablation should employ a minimum effective activity; reports increasingly suggest efficacy of low activities, e.g. 1110 MBq/30 mCi. OBJECTIVES, DESIGN, PATIENTS, AND INTERVENTIONS: We retrospectively studied the ablation capability and diagnostic utility of the Minidose protocol, two 740-MBq/20 mCi outpatient administrations, 6-18 months apart, plus related diagnostic procedures, in 160 consecutive (near-) totally thyroidectomized low-risk DTC (pT1/N0-Nx) patients. Successful ablation comprised negative 740-MBq whole-body scintigraphy with cervical uptake below 0.1%, negative stimulated thyroglobulin (STg) (<1 ng/ml, negative thyroglobulin antibodies), and negative Doppler ultrasonography (performed around Minidose 2). The study took place at a referral center. Minidose imaging found unsuspected nodal or distant metastases in nine of 160 patients (5.6%). Ablation success rates after one (two) 740-MBq activity (activites) were 75.9% (90.2%) in 145 (132) evaluable imaging-negative patients. Compared with thyroid hormone withdrawal, recombinant human TSH stimulation was associated with higher urinary iodine excretion/creatinine, lower cervical uptake, and more frequent ablation success after the first 740 MBq; success rates no longer differed significantly after both administrations. Patients with STg below 10 ng/ml at Minidose 1 were oftener ablated at Minidose 2 (odds ratio=13.9, 95% confidence interval=2.5-76.4, P<0.003), attaining 92.0% final ablation success after recombinant human TSH preparation, suggesting that one 740-MBq activity should suffice in this subgroup. All 81 evaluable patients with prolonged follow-up (mean 41.8±21.9 months after Minidose 1) had no evidence of disease at the last visit. The Minidose outpatient ablation protocol is effective and diagnostically useful in low-risk DTC.

  11. Body mass index was associated with upstaging and upgrading in patients with low-risk prostate cancer who met the inclusion criteria for active surveillance.

    Science.gov (United States)

    de Cobelli, Ottavio; Terracciano, Daniela; Tagliabue, Elena; Raimondi, Sara; Galasso, Giacomo; Cioffi, Antonio; Cordima, Giovanni; Musi, Gennaro; Damiano, Rocco; Cantiello, Francesco; Detti, Serena; Victor Matei, Deliu; Bottero, Danilo; Renne, Giuseppe; Ferro, Matteo

    2015-05-01

    Obesity is associated with an increased risk of high-grade prostate cancer (PCa). The effect of body mass index (BMI) as a predictor of progression in men with low-risk PCa has been only poorly assessed. In this study, we evaluated the association of BMI with progression in patients with low-risk PCa who met the inclusion criteria for the active surveillance (AS) protocol. We assessed 311 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level pT2) and upgraded (Gleason score ≥ 7; primary Gleason pattern 4) disease. Seminal vesicle invasion, positive lymph nodes, and tumor volume ≥ 0.5 ml were also recorded. We found that high BMI was significantly associated with upgrading, upstaging, and seminal vesicle invasion, whereas it was not associated with positive lymph nodes or large tumor volume. At multivariate analysis, 1 unit increase of BMI significantly increased the risk of upgrading, upstaging, seminal vesicle invasion, and any outcome by 21%, 23%, 27%, and 20%, respectively. The differences between areas under the receiver operating characteristics curves comparing models with and without BMI were statistically significant for upgrading (P = 0.0002), upstaging (P = 0.0007), and any outcome (P = 0.0001). BMI should be a selection criterion for inclusion of patients with low-risk PCa in AS programs. Our results support the idea that obesity is associated with worse prognosis and suggest that a close AS program is an appropriate treatment option for obese subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The effects of standing, lifting and noise exposure on preterm birth, growth restriction, and perinatal death in healthy low-risk working military women.

    Science.gov (United States)

    Magann, Everett F; Evans, Sharon F; Chauhan, Suneet P; Nolan, Thomas E; Henderson, Jenni; Klausen, Jack H; Newnham, John P; Morrison, John C

    2005-09-01

    The effects of standing, lifting and noise in low-risk, healthy pregnant women are uncertain. In the past, the heterogeneity of the populations studied, the limitations of the designs of the retrospective and case control studies, and a failure of some of the larger investigations to evaluate all the potential confounding variables has hampered many studies. The purpose of this investigation was to evaluate, throughout pregnancy, the effects of standing, repetitive lifting, and noise in the workplace compared with no standing, lifting or noise exposure, on maternal and perinatal outcomes in a large prospective study of a low-risk healthy population of working women cared for by a single group of health providers. This prospective observational study used an extensive questionnaire to collect antepartum, intrapartum, and postpartum information. Information was collected on the initial visit, each subsequent visit, and immediately after delivery. The participating women were divided into groups based on the amount of time spent standing, the amount and extent of repetitive lifting, and noise exposure in the workplace. Eight hundred and fourteen low-risk active duty women participated in this investigation over a 4-year period. Multivariate analysis with non-exposure compared with exposure reinforced the effect of standing on preterm labor (OR 1.80, 95% CI 1.05, 3.16) and preterm birth (OR 1.69, 95% CI 1.03, 2.80) and showed a trend toward an effect of noise exposure on preterm labor (OR 1.76, 95% CI 0.78, 3.39) after controlling for other exposures. This investigation suggests an association of occupational standing with preterm labor and preterm birth.

  13. Predictive value of general movements' quality in low-risk infants for minor neurological dysfunction and behavioural problems at preschool age.

    Science.gov (United States)

    Bennema, Anne N; Schendelaar, Pamela; Seggers, Jorien; Haadsma, Maaike L; Heineman, Maas Jan; Hadders-Algra, Mijna

    2016-03-01

    General movement (GM) assessment is a well-established tool to predict cerebral palsy in high-risk infants. Little is known on the predictive value of GM assessment in low-risk populations. To assess the predictive value of GM quality in early infancy for the development of the clinically relevant form of minor neurological dysfunction (complex MND) and behavioral problems at preschool age. Prospective cohort study. A total of 216 members of the prospective Groningen Assisted Reproductive Techniques (ART) cohort study were included in this study. ART did not affect neurodevelopmental outcome of these relatively low-risk infants born to subfertile parents. GM quality was determined at 2 weeks and 3 months. At 18 months and 4 years, the Hempel neurological examination was used to assess MND. At 4 years, parents completed the Child Behavior Checklist; this resulted in the total problem score (TPS), internalizing problem score (IPS), and externalizing problem score (EPS). Predictive values of definitely (DA) and mildly (MA) abnormal GMs were calculated. DA GMs at 2 weeks were associated with complex MND at 18 months and atypical TPS and IPS at 4 years (all ppredictive value of DA GMs at 2 weeks were rather low (13%-60%); specificity and negative predictive value were excellent (92%-99%). DA GMs at 3 months occurred too infrequently to calculate prediction. MA GMs were not associated with outcome. GM quality as a single predictor for complex MND and behavioral problems at preschool age has limited clinical value in children at low risk for developmental disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin.

    Science.gov (United States)

    Li, Quan; Cohn, David; Waller, Allyson; Backes, Floor; Copeland, Larry; Fowler, Jeffrey; Salani, Ritu; O'Malley, David

    2014-10-01

    The primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). This was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment with 4-step, one-solution desensitization protocols in the outpatient infusion center were included. Patients with delayed HSRs or immediate high-risk, moderate or severe HSRs were excluded. The primary end point was the rate of successful administrations of each course of platinums. From January 2011 to June 2013, eighteen eligible patients were evaluated for outpatient 4-step, one-solution desensitization. Thirteen patients had a history of HSRs to carboplatin and 5 with HSRs to cisplatin. All of 18 patients successfully completed 94 (98.9%) of 95 desensitization courses in the outpatient infusion center. Eight of 8 (100%) patients with initial mild HSRs completed 29/29 (100%) desensitization courses, and 9 of 10 (90%) of patients with initial moderate HSRs completed 65/66 (94%) desensitization courses. In total, 65/95 (68%) desensitizations resulted in no breakthrough reactions, and mild, moderate and severe breakthrough reactions were seen in 19%, 12% and 1% desensitizations, respectively. No patients were hospitalized during desensitization. The outpatient rapid, 4-step, one-solution desensitization protocol was effective and appeared safe among gynecologic oncology patients who experienced mild to low-risk, moderate HSRs to carboplatin/cisplatin. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Restrictions on Oral and Parenteral Intake for Low-risk Labouring Women in Hospitals Across Canada: A Cross-Sectional Study.

    Science.gov (United States)

    Chackowicz, Ariel; Spence, Andrea R; Abenhaim, Haim A

    2016-11-01

    The dietary intake allowed during the latent and active phases of labour varies between Canadian hospitals. Our objective was to document current restrictions on oral and parenteral intake for low-risk labouring women in hospitals across Canada. We carried out a cross-sectional study of 118 Canadian hospitals that have specialized birthing centres. Information on dietary protocols for low-risk women in labour was obtained from each hospital via a brief telephone interview with the head nurse of each birthing centre. Data were presented by stage of labour, both with and without epidural anaesthesia, and also by dextrose supplementation of intravenous fluids. If epidural anaesthesia was not used during the active phase of labour, oral intake was restricted to clear fluids and/or ice chips in 50.9% of surveyed hospitals and oral intake could include solid food in 38.1%. However, when epidural anaesthesia was used during the active phase of labour, oral intake was restricted to clear fluids and ice chips in 82.8% of surveyed hospitals, while oral intake could include solid food in 7.2%. Furthermore, in 77.5% of hospitals, not only was oral intake during active labour with epidural anaesthesia limited to clear fluids and/or ice chips, but in addition this restrictive diet was not supplemented with parenteral dextrose. The majority of low-risk pregnant women in Canadian hospitals are subjected to caloric restriction during the active phase of labour, especially when epidural anaesthesia is administered. Further studies on this subject are warranted because such pervasive practices may have important population effects on labouring women. Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

  16. Combined analyses of 20 common obesity susceptibility variants

    DEFF Research Database (Denmark)

    Sandholt, Camilla Helene; Sparsø, Thomas; Grarup, Niels

    2010-01-01

    Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes.......Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes....

  17. Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy

    International Nuclear Information System (INIS)

    Vainshtein, Jeffrey; Hamstra, Daniel A; Abu-Isa, Eyad; Olson, Karin B; Ray, Michael E; Sandler, Howard M; Normolle, Dan; Litzenberg, Dale W; Masi, Kathryn; Pan, Charlie

    2012-01-01

    Low-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT), while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ), we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT) could improve urinary health-related quality of life (HRQOL) while maintaining high rates of PCa control. Patients with National Comprehensive Cancer Network (NCCN) defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S-) IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3–5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC) Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months. From June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was −0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52). Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05). At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9–86). Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease. Compared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical control. The high rate of PSA failure and contralateral local failures in US-IMRT patients, despite

  18. Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy

    Directory of Open Access Journals (Sweden)

    Vainshtein Jeffrey

    2012-06-01

    Full Text Available Abstract Background Low-risk prostate cancer (PCa patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT, while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ, we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT could improve urinary health-related quality of life (HRQOL while maintaining high rates of PCa control. Methods Patients with National Comprehensive Cancer Network (NCCN defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S- IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3–5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months. Results From June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was −0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52. Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05. At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9–86. Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease. Conclusions Compared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical

  19. Development of industrial variant specification systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer

    be developed from a holistic and strategically anchored point of view. Another assumption is that this is a challenge for many industrial companies. Even though the literature presents many considerations on general issues covering new information technology, little work is found on the business perspectives...... are discussed. A list of structural variables and solution components has been created. These are related to four design aspects in the holistic system design covering the aspects of process design, selection of resources (such as hardware, software and humans), the design of information structures...... solution elements and structural variables to be used in the design of variant specification systems. The thesis presents a “top-down” procedure to be used to develop variant specification systems from a strategically anchored and holistic point of view. A methodology and related task variables...

  20. The Saccharomyces Genome Database Variant Viewer.

    Science.gov (United States)

    Sheppard, Travis K; Hitz, Benjamin C; Engel, Stacia R; Song, Giltae; Balakrishnan, Rama; Binkley, Gail; Costanzo, Maria C; Dalusag, Kyla S; Demeter, Janos; Hellerstedt, Sage T; Karra, Kalpana; Nash, Robert S; Paskov, Kelley M; Skrzypek, Marek S; Weng, Shuai; Wong, Edith D; Cherry, J Michael

    2016-01-04

    The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is the authoritative community resource for the Saccharomyces cerevisiae reference genome sequence and its annotation. In recent years, we have moved toward increased representation of sequence variation and allelic differences within S. cerevisiae. The publication of numerous additional genomes has motivated the creation of new tools for their annotation and analysis. Here we present the Variant Viewer: a dynamic open-source web application for the visualization of genomic and proteomic differences. Multiple sequence alignments have been constructed across high quality genome sequences from 11 different S. cerevisiae strains and stored in the SGD. The alignments and summaries are encoded in JSON and used to create a two-tiered dynamic view of the budding yeast pan-genome, available at http://www.yeastgenome.org/variant-viewer. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Angiography of histopathologic variants of synovial sarcoma

    International Nuclear Information System (INIS)

    Lois, J.F.; Fischer, H.J.; Mirra, J.M.; Gomes, A.S.; California Univ., Los Angeles

    1986-01-01

    Synovial sarcomas are rare soft tissue tumors which histopathologically can be divided into monophasic, biphasic and mixed variants. As part of a protocol for intra-arterial chemotherapy 12 patients with biopsy proven synovial sarcoma underwent angiography. The angiograms on these patients were reviewed to determine whether synovial sarcomas and their variants demonstrated a characteristic angiographic appearance. Synovial sarcomas appeared angiographically as soft tissue masses which showed a fine network of tumor vessels with an inhomogeneous capillary blush. Their degree of vascularity varied according to their histopathology. Monophasic synovial sarcomas demonstrated in general a higher degree of neovascularity than the biphasic form. This finding was also suggested by histopathologic analysis of the vessels in the tumor. Although angiography did not show a distinctive vascular pattern it may be useful to evaluate tumor size and vascularity. (orig.)

  2. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  3. Glucose oxidase variants with improved properities

    OpenAIRE

    Fischer, Rainer; Ostafe, Raluca; Prodanovic, Radivoje

    2014-01-01

    Source: WO14173822A3 [EN] The technology provided herein relates to novel variants of microbial glucose oxidase with improved properties, more specifically to polypeptides having glucose oxidase activity as their major enzymatic activity; to nucleic acid molecules encoding said glucose oxidases; vectors and host cells containing the nucleic acids and methods for producing the glucose oxidase; compositions comprising said glucose oxidase; methods for the preparation and production of such enzy...

  4. Unusual variant of Cantrell′s pentalogy?

    Directory of Open Access Journals (Sweden)

    Kumar Basant

    2008-01-01

    Full Text Available A 12-hour-old male infant presented with prolapsed abdominal content through a defect on left side of chest wall with respiratory distress. A thorough clinical examination suggested absence of ectopia cordis, abdominal wall defect, and any bony anomaly. The child expired after 6 hours of admission because of respiratory distress and electrolyte imbalance. Is congenital defect of chest wall associated with diaphragmatic hernia without ectopia cordis and omphalocele, an unusual variant of Cantrell′s pentalogy?

  5. Random Plant Viral Variants Attain Temporal Advantages During Systemic Infections and in Turn Resist other Variants of the Same Virus.

    Science.gov (United States)

    Zhang, Xiao-Feng; Guo, Jiangbo; Zhang, Xiuchun; Meulia, Tea; Paul, Pierce; Madden, Laurence V; Li, Dawei; Qu, Feng

    2015-10-20

    Infection of plants with viruses containing multiple variants frequently leads to dominance by a few random variants in the systemically infected leaves (SLs), for which a plausible explanation is lacking. We show here that SL dominance by a given viral variant is adequately explained by its fortuitous lead in systemic spread, coupled with its resistance to superinfection by other variants. We analyzed the fate of a multi-variant turnip crinkle virus (TCV) population in Arabidopsis and N. benthamiana plants. Both wild-type and RNA silencing-defective plants displayed a similar pattern of random dominance by a few variant genotypes, thus discounting a prominent role for RNA silencing. When introduced to plants sequentially as two subpopulations, a twelve-hour head-start was sufficient for the first set to dominate. Finally, SLs of TCV-infected plants became highly resistant to secondary invasions of another TCV variant. We propose that random distribution of variant foci on inoculated leaves allows different variants to lead systemic movement in different plants. The leading variants then colonize large areas of SLs, and resist the superinfection of lagging variants in the same areas. In conclusion, superinfection resistance is the primary driver of random enrichment of viral variants in systemically infected plants.

  6. The effect of prophylactic intravenous tranexamic acid on blood loss after vaginal delivery in women at low risk of postpartum haemorrhage: a double-blind randomised controlled trial.

    Science.gov (United States)

    Mirghafourvand, Mojgan; Mohammad-Alizadeh, Sakineh; Abbasalizadeh, Fatemeh; Shirdel, Mina

    2015-02-01

    To determine the effect of prophylactic tranexamic acid (TA) on calculated and measured blood loss after vaginal delivery in women at low risk of postpartum haemorrhage. In this double-blind randomised controlled trial, 120 women with a singleton pregnancy were randomly allocated to receive either one gram intravenous TA or placebo in addition to 10 IU oxytocin after delivery of the fetus. Calculated blood loss was determined based on haematocrit before delivery and 12-24 h postdelivery. The quantity of blood loss was measured during two time periods: from delivery of the fetus to placental expulsion and from placental expulsion to the end of the second hour after childbirth. The mean (SD) calculated total blood loss (519 (320) vs 659 (402) mL, P = 0.036) and measured blood loss from placental delivery to 2 h postpartum (69 (39) vs 108 (53) mL, P  1000 mL was lower in the TA group (7% vs 18%, P = 0.048). Prophylactic TA reduces blood loss after vaginal delivery in women with a low risk of postpartum haemorrhage. The prophylactic use of TA may reduce blood loss complications and enhance maternal health. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  7. Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

    Directory of Open Access Journals (Sweden)

    Kontny Udo

    2008-03-01

    Full Text Available Abstract Background Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. Methods A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. Results The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90% and specificity (85%. Conclusion These findings may have clinical implications for risk-based antimicrobial treatment strategies.

  8. Gender- and parity-specific reference charts for fetal size in low risk singleton pregnancies at the onset of the third trimester.

    Science.gov (United States)

    De Reu, Paul; Smits, Luc J; Oosterbaan, Herman P; Snijders, Rosalinde J; De Reu-Cuppens, Marga J; Nijhuis, Jan G

    2007-01-01

    To determine fetal growth in low risk pregnancies at the beginning of the third trimester and to assess the relative importance of fetal gender and maternal parity. Dutch primary care midwifery practice. Retrospective cohort study on 3641 singleton pregnancies seen at a primary care midwifery center in the Netherlands. Parameters used for analysis were fetal abdominal circumference (AC), fetal head circumference (HC), gestational age, fetal gender and maternal parity. Regression analysis was applied to describe variation in AC and HC with gestational age. Means and standard deviations in the present population were compared with commonly used reference charts. Multiple regression analysis was applied to examine whether gender and parity should be taken into account. The fetal AC and HC increased significantly between the 27th and the 33rd week of pregnancy (AC r2=0.3652, Pgender was a significant determinant for both AC (PParity contributed significantly to AC only but the difference was small (beta=0.00464). At the beginning of the third trimester, fetal size is associated with fetal gender and, to a lesser extent, with parity. Some fetal growth charts (e.g., Chitty et al.) are more suitable for the low-risk population in the Netherlands than others.

  9. Intelligent Structured Intermittent Auscultation (ISIA): evaluation of a decision-making framework for fetal heart monitoring of low-risk women

    Science.gov (United States)

    2014-01-01

    Background Research-informed fetal monitoring guidelines recommend intermittent auscultation (IA) for fetal heart monitoring for low-risk women. However, the use of cardiotocography (CTG) continues to dominate many institutional maternity settings. Methods A mixed methods intervention study with before and after measurement was undertaken in one secondary level health service to facilitate the implementation of an initiative to encourage the use of IA. The intervention initiative was a decision-making framework called Intelligent Structured Intermittent Auscultation (ISIA) introduced through an education session. Results Following the intervention, medical records review revealed an increase in the use of IA during labour represented by a relative change of 12%, with improved documentation of clinical findings from assessments, and a significant reduction in the risk of receiving an admission CTG (RR 0.75, 95% CI, 0.60 – 0.95, p = 0.016). Conclusion The ISIA informed decision-making framework transformed the practice of IA and provided a mechanism for knowledge translation that enabled midwives to implement evidence-based fetal heart monitoring for low risk women. PMID:24884597

  10. Outcome of planned home and hospital births among low-risk women in Iceland in 2005-2009: a retrospective cohort study.

    Science.gov (United States)

    Halfdansdottir, Berglind; Smarason, Alexander Kr; Olafsdottir, Olof A; Hildingsson, Ingegerd; Sveinsdottir, Herdis

    2015-03-01

    At 2.2 percent in 2012, the home birth rate in Iceland is the highest in the Nordic countries and has been rising rapidly in the new millennium. The objective of this study was to compare the outcomes of planned home births and planned hospital births in comparable low-risk groups in Iceland. The study is a retrospective cohort study comparing the total population of 307 planned home births in Iceland in 2005-2009 to a matched 1:3 sample of 921 planned hospital births. Regression analysis, adjusted for confounding variables, was performed for the primary outcome variables. The rate of oxytocin augmentation, epidural analgesia, and postpartum hemorrhage was significantly lower when labor started as a planned home birth. Differences in the rates of other primary outcome variables were not significant. The home birth group had lower rates of operative birth and obstetric anal sphincter injury. The rate of 5-minute Apgar score home and hospital birth groups, but the home birth group had a higher rate of neonatal intensive care unit admission. Intervention and adverse outcome rates in both study groups, including transfer rates, were higher among primiparas than multiparas. Oxytocin augmentation, epidural analgesia, and postpartum hemorrhage rates were significantly interrelated. This study adds to the growing body of evidence that suggests that planned home birth for low-risk women is as safe as planned hospital birth. © 2015 Wiley Periodicals, Inc.

  11. The impact of umbilical and uterine artery Doppler indices on antenatal course, labor and delivery in a low-risk primigravid population.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2012-02-01

    AIMS: To evaluate the impact of umbilical and uterine artery Doppler in the second and third trimester on antenatal course, labor and delivery in a low-risk primigravid population. METHODS: Prospective recruitment of 1011 low-risk primigravidas with uterine and umbilical artery Doppler assessment at 22-24 weeks and 36 weeks. All mothers and infants were reviewed postnatally with a retrospective analysis of ultrasound and clinical outcome data. RESULTS: Elevated uterine artery indices were associated with increased rates of threatened miscarriage, higher rates of pre-eclampsia (PET) and a higher incidence of fetal birth weight <2nd and 9th centile for gestation. Uterine artery pulsatility index (PI) >95th centile for gestation was associated with statistically higher rates of small-for-gestational age (SGA) infants. Elevated umbilical artery indices were associated with higher rates of induction of labor and a higher incidence of fetal birth weight infants <2nd and 9th centile for gestation. Umbilical artery PI >95th centile for gestation was associated with statistically higher rates of SGA infants. CONCLUSION: Elevated uterine and umbilical artery indices are associated with higher rates of maternal and fetal disease.

  12. Quality of antenatal care provided by nurse midwives in an Urban health centre with regard to low-risk antenatal mothers

    Directory of Open Access Journals (Sweden)

    Ruby Angeline Pricilla

    2017-01-01

    Full Text Available Background:India contributes to 19% of the global maternal deaths. Good quality antenatal care can prevent maternal deaths by early detection of complications and maintaining maternal health. There are few studies documenting quality of antenatal care in India. This study aimed to document the antenatal services provided by nurse midwives to low-risk pregnant mothers from an urban population. Aims: The primary objective was to describe the quality of the antenatal care provided by nurse midwives of an urban health centre with regard to low-risk mothers. The secondary objective was to document the maternal and early neonatal outcomes of the enrolled mothers during the period of study. Methods: This prospective cohort study was done on 200 pregnant women who had antenatal care by nurse midwives between April 2014 and November 2014. The quality of care was assessed by a checklist adapted from World Health Organization (WHO. Results: We report that the quality of antenatal care for all domains was above 90% except for the health education domain, which was poor with regard to breastfeeding and family planning in the enrolled 200 pregnant women. Conclusion: Our study concluded that trained nurse midwives when regularly monitored, audited and linked with reliable referral facilities can deliver good quality antenatal care.

  13. Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer

    International Nuclear Information System (INIS)

    Zeliadt, Steven B.; Potosky, Arnold L.; Penson, David F.; Etzioni, Ruth

    2006-01-01

    Background: The use of adjuvant androgen deprivation therapy (ADT) combined with radiotherapy has become common in low-risk patients, although clinical trials have focused primarily on high-risk patients. This study examines the effectiveness of adjuvant ADT combined with radiotherapy for a wide range of patients treated in the 1990s. Methods and Materials: Prostate cancer survival was examined in a population based cohort of 31,643 patients aged 65 to 85 years who were diagnosed with nonmetastatic prostate cancer and treated with external beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods were used to control for selection bias. Results: Patients with stage T3/T4 disease who received adjuvant ADT experienced improved 5-year and 8-year survival. No survival advantage was observed for men with T1/T2 disease during this interval. Conclusion: High-risk patients who receive primary radiotherapy have benefited from adjuvant ADT, whereas low-risk patients with disease confined to the prostate have not yet benefited from adjuvant therapy within the first 8 years after treatment. These findings are consistent with practice guidelines, which recommend adjuvant ADT for patients with high-risk disease

  14. Limiting overdiagnosis of low-risk prostate cancer through an evaluation of the predictive value of transrectal and power Doppler ultrasonography.

    Science.gov (United States)

    Sauvain, Jean Luc; Sauvain, Elise; Papavero, Roger; Louis, Didier; Rohmer, Paul

    2016-12-01

    Overdiagnosis induced by prostate cancer screening makes necessary a better selection of candidate patients for prostate biopsy. The objective of our study is to assess the probability of having a high- or low-risk lesion that could require active surveillance (AS) after biopsies and a normal or abnormal examination, including transrectal and power Doppler ultrasonography (TRUS-PDS). Four hundred and twenty-nine consecutive patients with a PSA level risk of a biological recurrence and Dall'Era's criteria to assess possible AS. The TRUS-PDS was considered positive if one biopsy was positive in the same sextant as the suspect image. One hundred and seventy-seven out of 429 (41 %) T1c cancers were diagnosed; 131 out of 177 (74 %) could be qualified as low risk, and 119 out of 177 (67 %) could require AS. The TRUS-PDS was normal in 285 of 429 patients (66 %). With a normal TRUS-PDS, the probability of not having cancer with a high or intermediate risk was 96 % (negative predictive value). With an abnormal TRUS-PDS, the probability of having a positive biopsy was 59 %, and the probability of having a significant cancer was 30 %, according to the Dall'Era criteria. When TRUS-PDS was normal, these probabilities significantly decreased to 32 and 5 %, respectively ( p  risk of high- or intermediate-risk cancer.

  15. Maternal and neonatal outcomes in birth centers versus hospitals among women with low-risk pregnancies in Japan: A retrospective cohort study.

    Science.gov (United States)

    Kataoka, Yaeko; Masuzawa, Yuko; Kato, Chiho; Eto, Hiromi

    2018-01-01

    In order for low-risk pregnant women to base birth decisions on the risks and benefits, they need evidence of birth outcomes from birth centers. The purpose of this study was to describe and compare the maternal and neonatal outcomes of low-risk women who gave birth in birth centers and hospitals in Japan. The participants were 9588 women who had a singleton vaginal birth at 19 birth centers and two hospitals in Tokyo. The data were collected from their medical records, including their age, parity, mode of delivery, maternal position at delivery, duration of labor, intrapartum blood loss, perineal trauma, gestational weeks at birth, birth weight, Apgar score, and stillbirths. For the comparison of birth centers with hospitals, adjusted odds ratios for the birth outcomes were estimated by using a logistic regression analysis. The number of women who had a total blood loss of >1 L was higher in the midwife-led birth centers than in the hospitals but the incidence of perineal lacerations was lower. There were fewer infants who were born at the midwife-led birth centers with Apgar scores of birth centers and hospitals. Additional research, using matched baseline characteristics, could clarify the comparisons for maternal and neonatal outcomes. © 2017 Japan Academy of Nursing Science.

  16. Spatially variant periodic structures in electromagnetics

    Science.gov (United States)

    Rumpf, Raymond C.; Pazos, Javier J.; Digaum, Jennefir L.; Kuebler, Stephen M.

    2015-01-01

    Spatial transforms are a popular technique for designing periodic structures that are macroscopically inhomogeneous. The structures are often required to be anisotropic, provide a magnetic response, and to have extreme values for the constitutive parameters in Maxwell's equations. Metamaterials and photonic crystals are capable of providing these, although sometimes only approximately. The problem still remains about how to generate the geometry of the final lattice when it is functionally graded, or spatially varied. This paper describes a simple numerical technique to spatially vary any periodic structure while minimizing deformations to the unit cells that would weaken or destroy the electromagnetic properties. New developments in this algorithm are disclosed that increase efficiency, improve the quality of the lattices and provide the ability to design aplanatic metasurfaces. The ability to spatially vary a lattice in this manner enables new design paradigms that are not possible using spatial transforms, three of which are discussed here. First, spatially variant self-collimating photonic crystals are shown to flow unguided waves around very tight bends using ordinary materials with low refractive index. Second, multi-mode waveguides in spatially variant band gap materials are shown to guide waves around bends without mixing power between the modes. Third, spatially variant anisotropic materials are shown to sculpt the near-field around electric components. This can be used to improve electromagnetic compatibility between components in close proximity. PMID:26217058

  17. Warty Carcinoma Penis: An Uncommon Variant

    Directory of Open Access Journals (Sweden)

    Sushma Thapa

    2017-01-01

    Full Text Available Penile carcinoma frequency varies widely in different parts of the world and comprises 1–10% of all the malignancies in males. Majority of the cases of penile carcinoma are squamous cell carcinoma of penis comprising 60% to 70% of all cases. Warty carcinoma of penis is an unusual neoplasm and a variant of penile squamous cell carcinoma comprising 5%–10% of all the variants. The other histological variants include basaloid, verrucous, papillary, sarcomatous, mixed, and adenosquamous carcinoma. The various histological entities with an exophytic papillary lesions including warty carcinoma are together referred to as the “verruciform” group of neoplasms. The warty carcinoma has to be differentiated from these lesions and is typically distinguished by histological features of hyperkeratosis, arborescent papillomatosis, acanthosis, and prominent koilocytosis with nuclear pleomorphism. We present a case of 65-year-old male with growth measuring 6×4 cm in the penis who underwent total penectomy and was diagnosed as warty carcinoma penis.

  18. Cryptanalysis of RSA and its variants

    CERN Document Server

    Hinek, M Jason

    2009-01-01

    Thirty years after RSA was first publicized, it remains an active research area. Although several good surveys exist, they are either slightly outdated or only focus on one type of attack. Offering an updated look at this field, Cryptanalysis of RSA and Its Variants presents the best known mathematical attacks on RSA and its main variants, including CRT-RSA, multi-prime RSA, and multi-power RSA. Divided into three parts, the book first introduces RSA and reviews the mathematical background needed for the majority of attacks described in the remainder of the text. It then brings together all of the most popular mathematical attacks on RSA and its variants. For each attack presented, the author includes a mathematical proof if possible or a mathematical justification for attacks that rely on assumptions. For the attacks that cannot be proven, he gives experimental evidence to illustrate their practical effectiveness. Focusing on mathematical attacks that exploit the structure of RSA and specific parameter choic...

  19. MR imaging of the ankle: Normal variants

    International Nuclear Information System (INIS)

    Noto, A.M.; Cheung, Y.; Rosenberg, Z.S.; Norman, A.; Leeds, N.E.

    1987-01-01

    Thirty asymptomatic ankles were studied with high-resolution surface coil MR imaging. The thirty ankles were reviewed for identification or normal structures. The MR appearance of the deltoid and posterior to talo-fibular ligaments, peroneous brevis and longus tendons, and posterior aspect of the tibial-talar joint demonstrated several normal variants not previously described. These should not be misinterpreted as pathologic processes. The specific findings included (1) cortical irregularity of the posterior tibial-talar joint in 27 of 30 cases which should not be mistaken for osteonecrois; (2) normal posterior talo-fibular ligament with irregular and frayed inhomogeneity, which represents a normal variant in seven of ten cases; and (3) fluid in the shared peroneal tendons sheath which may be confused for a longitudinal tendon tear in three of 30 cases. Ankle imaging with the use of MR is still a relatively new procedure. Further investigation is needed to better define normal anatomy as well as normal variants. The authors described several structures that normally present with variable MR imaging appearances. This is clinically significant in order to maintain a high sensitivity and specificity in MR imaging interpretation

  20. Annotating pathogenic non-coding variants in genic regions.

    Science.gov (United States)

    Gelfman, Sahar; Wang, Quanli; McSweeney, K Melodi; Ren, Zhong; La Carpia, Francesca; Halvorsen, Matt; Schoch, Kelly; Ratzon, Fanni; Heinzen, Erin L; Boland, Michael J; Petrovski, Slavé; Goldstein, David B

    2017-08-09

    Identifying the underlying causes of disease requires accurate interpretation of genetic variants. Current methods ineffectively capture pathogenic non-coding variants in genic regions, resulting in overlooking synonymous and intronic variants when searching for disease risk. Here we present the Transcript-inferred Pathogenicity (TraP) score, which uses sequence context alterations to reliably identify non-coding variation that causes disease. High TraP scores single out extremely rare variants with lower minor allele frequencies than missense variants. TraP accurately distinguishes known pathogenic and benign variants in synonymous (AUC = 0.88) and intronic (AUC = 0.83) public datasets, dismissing benign variants with exceptionally high specificity. TraP analysis of 843 exomes from epilepsy family trios identifies synonymous variants in known epilepsy genes, thus pinpointing risk factors of disease from non-coding sequence data. TraP outperforms leading methods in identifying non-coding variants that are pathogenic and is therefore a valuable tool for use in gene discovery and the interpretation of personal genomes.While non-coding synonymous and intronic variants are often not under strong selective constraint, they can be pathogenic through affecting splicing or transcription. Here, the authors develop a score that uses sequence context alterations to predict pathogenicity of synonymous and non-coding genetic variants, and provide a web server of pre-computed scores.

  1. Microsatellite Instability Use in Mismatch Repair Gene Sequence Variant Classification

    Directory of Open Access Journals (Sweden)

    Bryony A. Thompson

    2015-03-01

    Full Text Available Inherited mutations in the DNA mismatch repair genes (MMR can cause MMR deficiency and increased susceptibility to colorectal and endometrial cancer. Microsatellite instability (MSI is the defining molecular signature of MMR deficiency. The clinical classification of identified MMR gene sequence variants has a direct impact on the management of patients and their families. For a significant proportion of cases sequence variants of uncertain clinical significance (also known as unclassified variants are identified, constituting a challenge for genetic counselling and clinical management of families. The effect on protein function of these variants is difficult to interpret. The presence or absence of MSI in tumours can aid in determining the pathogenicity of associated unclassified MMR gene variants. However, there are some considerations that need to be taken into account when using MSI for variant interpretation. The use of MSI and other tumour characteristics in MMR gene sequence variant classification will be explored in this review.

  2. Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals.

    Science.gov (United States)

    Bergholdt, Helle K M; Nordestgaard, Børge G; Ellervik, Christina

    2015-08-01

    High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown. We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obesity, observationally and genetically. In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype [polymorphism (rs4988235) upstream from the lactase (LCT) gene], where TT and TC genotypes are associated with lactase persistence and CC with nonpersistence. Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk intake was 5 glasses/wk (IQR: 0-10) for lactase TT/TC persistence and 3 (0-7) for CC nonpersistence. Genetically for lactase TT/TC persistence compared with CC nonpersistence, the OR was 0.96 (0.86, 1.08; P = 0.50) for type 2 diabetes and 1.06 (1.00, 1.12; P = 0.04) for overweight-obesity. In a stratified analysis for type 2 diabetes, corresponding values in those with and without milk intake were 0.88 (0.76, 1.03; P = 0.11) and 1.35 (1.07, 1.70; P = 0.01) (P-interaction: 0.002), whereas no gene-milk interaction on overweight-obesity was found. For a 1-glass/wk higher milk intake, the genetic risk ratio for type 2 diabetes was 0.99 (0.93, 1.06), and the corresponding observational risk was 1.01 (1.00, 1.01). For overweight-obesity, the corresponding values were 1.01 (1.00, 1.02) genetically and 1.00 (1.00, 1.01) observationally. High milk intake is not associated with a low risk of type 2 diabetes or overweight-obesity, observationally or genetically via lactase persistence. The higher risk of type 2 diabetes in lactase-persistent individuals without milk intake likely is explained by collider stratification

  3. An assessment of Prostate Cancer Research International: Active Surveillance (PRIAS) criteria for active surveillance of clinically low-risk prostate cancer patients

    Science.gov (United States)

    da Silva, Vitor; Cagiannos, Ilias; Lavallée, Luke T.; Mallick, Ranjeeta; Witiuk, Kelsey; Cnossen, Sonya; Eastham, James A.; Fergusson, Dean A.; Morash, Chris; Breau, Rodney H.

    2017-01-01

    Introduction Active surveillance is a strategy to delay or prevent treatment of indolent prostate cancer. The Prostate Cancer Research International: Active Surveillance (PRIAS) criteria were developed to select patients for prostate cancer active surveillance. The objective of this study was to compare pathological findings from PRIAS-eligible and PRIAS-ineligible clinically low-risk prostate cancer patients. Methods A D’Amico low-risk cohort of 1512 radical prostatectomy patients treated at The Ottawa Hospital or Memorial Sloan Kettering Cancer Centre between January 1995 and December 2007 was reviewed. Pathological outcomes (pT3 tumours, Gleason sum ≥7, lymph node metastases, or a composite) and clinical outcomes (prostate-specific antigen [PSA] recurrence, secondary cancer treatments, and death) were compared between PRIAS-eligible and PRIAS-ineligible cohorts. Results The PRIAS-eligible cohort (n=945) was less likely to have Gleason score ≥7 (odds ratio [OR] 0.61; 95% confidence interval [CI] 0.49–0.75), pT3 (OR 0.41; 95% CI 0.31–0.55), nodal metastases (OR 0.37; 95% CI 0.10–1.31), or any adverse feature (OR 0.56; 95% CI 0.45–0.69) compared to the PRIAS-ineligible cohort. The probability of any adverse pathology in the PRIAS-eligible cohort was 41% vs. 56% in the PRIAS-ineligible cohort. At median follow-up of 3.7 years, 72 (4.8%) patients had a PSA recurrence, 24 (1.6%) received pelvic radiation, and 13 (0.9%) received androgen deprivation. No difference was detected for recurrence-free and overall survival between groups (recurrence hazard ratio [HR] 0.71; 95% CI 0.46–1.09 and survival HR 0.72; 95% CI 0.36–1.47). Conclusions Low-risk prostate cancer patients who met PRIAS eligibility criteria are less likely to have higher-risk cancer compared to those who did not meet at least one of these criteria. PMID:28798822

  4. Audit of a new model of birth care for women with low risk pregnancies in South Africa: the primary care onsite midwife-led birth unit (OMBU).

    Science.gov (United States)

    Hofmeyr, George Justus; Mancotywa, Thozeka; Silwana-Kwadjo, Nomvula; Mgudlwa, Batembu; Lawrie, Theresa A; Gülmezoglu, Ahmet Metin

    2014-12-20

    South Africa's health system is based on the primary care model in which low-risk maternity care is provided at community health centres and clinics, and 'high-risk' care is provided at secondary/tertiary hospitals. This model has the disadvantage of delays in the management of unexpected intrapartum complications in otherwise low-risk pregnancies, therefore, there is a need to re-evaluate the models of birth care in South Africa. To date, two primary care onsite midwife-led birth units (OMBUs) have been established in the Eastern Cape. OMBUs are similar to alongside midwifery units but have been adapted to the South African health system in that they are staffed, administered and funded by the primary care service. They allow women considered to be at 'low risk' to choose between birth in a community health centre and birth in the OMBU. The purpose of this audit was to evaluate the impact of establishing an OMBU at Frere Maternity Hospital in East London, South Africa, on maternity services. We conducted an audit of routinely collected data from Frere Maternity Hospital over two 12 month periods, before and after the OMBU opened. Retrospectively retrieved data included the number of births, maternal and perinatal deaths, and mode of delivery. After the OMBU opened at Frere Maternity Hospital, the total number of births on the hospital premises increased by 16%. The total number of births in the hospital obstetric unit (OU) dropped by 9.3%, with 1611 births out of 7375 (22%) occurring in the new OMBU. The number of maternal and perinatal deaths was lower in the post-OMBU period compared with the pre-OMBU period. These improvements cannot be assumed to be the result of the intervention as observational studies are prone to bias. The mortality data should be interpreted with caution as other factors such as change in risk profile may have contributed to the death reductions. There are many additional advantages for women, hospital staff and primary care staff with

  5. Rising cesarean deliveries among apparently low-risk mothers at university teaching hospitals in Jordan: analysis of population survey data, 2002–2012

    Science.gov (United States)

    Rifai, Rami Al

    2014-01-01

    Background: Cesarean delivery conducted without medical indication places mothers and infants at risk for adverse outcomes. This study assessed changes in trends of, and factors associated with, cesarean deliveries in Jordan, from 2002 to 2012. Methods: Data for ever-married women ages 15–49 years from the 2002, 2007, and 2012 Jordan Population and Family Health Surveys were used. Analyses were restricted to mothers who responded to a question regarding the hospital-based mode of delivery for their last birth occurring within the 5 years preceding each survey (2002, N = 3,450; 2007, N = 6,307; 2012, N = 6,365). Normal birth weight infants and singleton births were used as markers for births that were potentially low risk for cesarean delivery, because low/high birth weight and multiple births are among the main obstetric variables that have been documented to increase risk of cesareans. Weighted descriptive and multivariate analyses were conducted using 4 logistic regression models: (1) among all mothers; and among mothers stratified (2) by place of delivery; (3) by birth weight of infants; and (4) by singleton vs. multiple births. Results: The cesarean delivery rate increased significantly over time, from 18.2% in 2002, to 20.1% in 2007, to 30.3% in 2012. Place of delivery, birth weight, and birth multiplicity were significantly associated with cesarean delivery after adjusting for confounding factors. Between 2002 and 2012, the rate increased by 99% in public hospitals vs. 70% in private hospitals; by 93% among normal birth weight infants vs. 73% among low/high birth weight infants; and by 92% among singleton births vs. 29% among multiple births. The changes were significant across all categories except among multiple births. Further stratification revealed that the cesarean delivery rate was 2.29 times higher in university teaching hospitals (UTHs) than in private hospitals (Pcesarean delivery rate among births that may have been at low risk for

  6. Genetic Variants Associated with Circulating Parathyroid Hormone.

    Science.gov (United States)

    Robinson-Cohen, Cassianne; Lutsey, Pamela L; Kleber, Marcus E; Nielson, Carrie M; Mitchell, Braxton D; Bis, Joshua C; Eny, Karen M; Portas, Laura; Eriksson, Joel; Lorentzon, Mattias; Koller, Daniel L; Milaneschi, Yuri; Teumer, Alexander; Pilz, Stefan; Nethander, Maria; Selvin, Elizabeth; Tang, Weihong; Weng, Lu-Chen; Wong, Hoi Suen; Lai, Dongbing; Peacock, Munro; Hannemann, Anke; Völker, Uwe; Homuth, Georg; Nauk, Matthias; Murgia, Federico; Pattee, Jack W; Orwoll, Eric; Zmuda, Joseph M; Riancho, Jose Antonio; Wolf, Myles; Williams, Frances; Penninx, Brenda; Econs, Michael J; Ryan, Kathleen A; Ohlsson, Claes; Paterson, Andrew D; Psaty, Bruce M; Siscovick, David S; Rotter, Jerome I; Pirastu, Mario; Streeten, Elizabeth; März, Winfried; Fox, Caroline; Coresh, Josef; Wallaschofski, Henri; Pankow, James S; de Boer, Ian H; Kestenbaum, Bryan

    2017-05-01

    Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies ( n =22,653 and n =6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 ( P =4.2 × 10 -53 ), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 ( P =6.6 × 10 -17 ), rs219779 adjacent to CLDN14 ( P =3.5 × 10 -16 ), rs4443100 near RTDR1 ( P =8.7 × 10 -9 ), and rs73186030 near CASR ( P =4.8 × 10 -8 ). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued. Copyright © 2017 by the American Society of Nephrology.

  7. Human papillomavirus genotypes and phylogenetic analysis of HPV-16 variants in HIV-1 infected subjects in Italy.

    Science.gov (United States)

    Tanzi, Elisabetta; Amendola, Antonella; Bianchi, Silvia; Fasolo, M Michela; Beretta, Rosangela; Pariani, Elena; Zappa, Alessandra; Frati, Elena; Orlando, Giovanna

    2009-05-29

    A cross-sectional study was carried out to improve the state of evidence regarding the spectrum of HPV types and HPV-16 LCR variants circulating among men and women infected with HIV-1 in Italy. This study, conducted in 518 HIV-positive subjects (346 males and 172 females), showed a high prevalence of HPV anal infections (88.7%) in men and of cervical infections (65.1%) in women. A wide spectrum of HPV genotypes has been observed, as both single and multiple infections. Low-risk HPV types 6, 11 and 61 were frequently detected. HPV-16 was the prevalent high-risk type. Fourteen different HPV-16 LCR variants were found. Ten belonged to the European lineage (78.7% were detected in Italian subjects and 21.3% in foreign-born, all homo/bisexual men), two to the Asiatic lineage and two to the African-2 lineage. This study underlines the great genotypic heterogeneity characterizing anal and cervical HPV infections and the marked polymorphism of the predominant HPV-16 in this high-risk population in Italy.

  8. Intermittent auscultation of fetal heart rate during labour - a widely accepted technique for low risk pregnancies: but are the current national guidelines robust and practical?

    Science.gov (United States)

    Sholapurkar, S L

    2010-01-01

    Intermittent auscultation of fetal heart rate is an accepted practice in low risk labours in many countries. National guidelines on intrapartum fetal monitoring were critically reviewed regarding timing and frequency of intermittent auscultation. Hypothetical but plausible examples are presented to illustrate that it may be possible to miss significant fetal distress with strict adherence to current guidelines. Opinion is forwarded that intermittent auscultation should be performed for 60 seconds before and after three contractions over about 10 min every half an hour in the first stage of labour. Reasons are put forward to show how this could be more practical and patient friendly and at the same time could improve detection of fetal distress. The current recommendation of intermittent auscultation every 15 min in the first stage is associated with poor compliance and leads to unnecessary burden, stress and medicolegal liability for birth attendants. Modification of current national guidelines would be desirable.

  9. Brain Derived Neurotrophic Factor (BDNF) levels as a possible predictor of psychopathology in healthy twins at high and low risk for affective disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Kessing, Lars Vedel

    2014-01-01

    and low risk twins, respectively). Participants were followed up longitudinally with questionnaires at 6-month intervals for mean seven years and then reassessed with a personal interview to obtain information about whether they had developed psychiatric illness. At follow-up 36 participants (15.4%) had...... developed psychiatric disorder. Cox regression analysis revealed that BDNF levels at baseline were not associated with onset of illness in this explorative study. Further, two-way interactions between BDNF levels and the Val66Met polymorphism or between familial risk and the Val66Met polymorphism did......Brain Derived Neurotrophic Factor (BDNF) is a potential biomarker of affective disorder. However, longitudinal studies evaluating a potential predictive role of BDNF on subsequent psychopathology are lacking. The aim of this study was to investigate whether BDNF alone or in interaction...

  10. The HEART score is useful to predict cardiovascular risks and reduces unnecessary cardiac imaging in low-risk patients with acute chest pain.

    Science.gov (United States)

    Dai, Siping; Huang, Bo; Zou, Yunliang; Guo, Jianbin; Liu, Ziyong; Pi, Dangyu; Qiu, Yunhong; Xiao, Chun

    2018-06-01

    The present study was to investigate whether the HEART score can be used to evaluate cardiovascular risks and reduce unnecessary cardiac imaging in China.Acute coronary syndrome patients with the thrombosis in myocardial infarction risk score risk HEART score group and 2 patients (1.5%) in the high risk HEART score group had cardiovascular events. The sensitivity of HEART score to predict cardiovascular events was 100% and the specificity was 46.7%. The potential unnecessary cardiac testing was 46.3%. Cox proportional hazards regression analysis showed that per one category increase of the HEART score was associated with nearly 1.3-fold risk of cardiovascular events.In the low-risk acute chest pain patients, the HEART score is useful to physicians in evaluating the risk of cardiovascular events within the first 30 days. In addition, the HEART score is also useful in reducing the unnecessary cardiac imaging.

  11. Complex branchial fistula: a variant arch anomaly.

    Science.gov (United States)

    De Caluwé, D; Hayes, R; McDermott, M; Corbally, M T

    2001-07-01

    A 5-year-old boy presented with an infected left-sided branchial fistula. Despite antibiotic treatment and repeated excision of the fistula, purulent discharge from the wound persisted. Three-dimensional computed tomography (3D CT) reconstruction greatly facilitated the diagnosis and management of this case by showing the course of the fistulous tract. The complexity of the tract suggests that this represents a variant arch anomaly because it contains features of first, second, third, and fourth arch remnants. Copyright 2001 by W.B. Saunders Company.

  12. Anatomy, normal variants, and basic biomechanics

    International Nuclear Information System (INIS)

    Berquist, T.H.; Johnson, K.A.

    1989-01-01

    This paper reports on the anatomy and basic functions of the foot and ankle important to physicians involved in imaging procedures, clinical medicine, and surgery. New radiographic techniques especially magnetic resonance imaging, provide more diagnostic information owing to improved tissue contrast and the ability to obtain multiple image planes (axial, sagittal, coronal, oblique). Therefore, a thorough knowledge of skeletal and soft tissue anatomy is even more essential. Normal variants must also be understood in order to distinguish normal from pathologic changes in the foot and ankle. A basic understanding of biomechanics is also essential for selecting the proper diagnostic techniques

  13. Research progress of behavioral variant frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Xiao-hua GU

    2015-07-01

    Full Text Available There is no epidemiological data of frontotemporal dementia (FTD in China. The application of updated diagnostic criteria, publishing of frontotemporal lobar degeneration (FTLD consensus in China, development of multimodal imaging and biomarkers promote the clinical understanding on behavioral variant frontotemporal dementia (bvFTD. There is still no drugs treating FTD approved by U.S. Food and Drug Administration (FDA. Multidisciplinary intervention may delay the progression of bvFTD. DOI: 10.3969/j.issn.1672-6731.2015.07.006

  14. Oral fibrolipoma: A rare histological variant

    Directory of Open Access Journals (Sweden)

    Treville Pereira

    2014-01-01

    Full Text Available Lipomas are benign soft tissue mesenchymal neoplasms. Fibrolipoma is a histological variant of lipoma that mostly affects the buccal mucosa and causes functional and cosmetic disabilities. The diagnosis and differentiation of fibrolipoma with clinically similar lesions such as fibroma and pleomorphic adenoma is very essential for a correct treatment plan and complete follow-up. This article presents a case of a 35-year-old female with a fibrolipoma on the lingual marginal gingiva of the mandibular left third molar.

  15. Performance comparison of various time variant filters

    Energy Technology Data Exchange (ETDEWEB)

    Kuwata, M [JEOL Engineering Co. Ltd., Akishima, Tokyo (Japan); Husimi, K

    1996-07-01

    This paper describes the advantage of the trapezoidal filter used in semiconductor detector system comparing with the other time variant filters. The trapezoidal filter is the compose of a rectangular pre-filter and a gated integrator. We indicate that the best performance is obtained by the differential-integral summing type rectangular pre-filter. This filter is not only superior in performance, but also has the useful feature that the rising edge of the output waveform is linear. We introduce an example of this feature used in a high-energy experiment. (author)

  16. The AFFORD clinical decision aid to identify emergency department patients with atrial fibrillation at low risk for 30-day adverse events.

    Science.gov (United States)

    Barrett, Tyler W; Storrow, Alan B; Jenkins, Cathy A; Abraham, Robert L; Liu, Dandan; Miller, Karen F; Moser, Kelly M; Russ, Stephan; Roden, Dan M; Harrell, Frank E; Darbar, Dawood

    2015-03-15

    There is wide variation in the management of patients with atrial fibrillation (AF) in the emergency department (ED). We aimed to derive and internally validate the first prospective, ED-based clinical decision aid to identify patients with AF at low risk for 30-day adverse events. We performed a prospective cohort study at a university-affiliated tertiary-care ED. Patients were enrolled from June 9, 2010, to February 28, 2013, and followed for 30 days. We enrolled a convenience sample of patients in ED presenting with symptomatic AF. Candidate predictors were based on ED data available in the first 2 hours. The decision aid was derived using model approximation (preconditioning) followed by strong bootstrap internal validation. We used an ordinal outcome hierarchy defined as the incidence of the most severe adverse event within 30 days of the ED evaluation. Of 497 patients enrolled, stroke and AF-related death occurred in 13 (3%) and 4 (aid included the following: age, triage vitals (systolic blood pressure, temperature, respiratory rate, oxygen saturation, supplemental oxygen requirement), medical history (heart failure, home sotalol use, previous percutaneous coronary intervention, electrical cardioversion, cardiac ablation, frequency of AF symptoms), and ED data (2 hours heart rate, chest radiograph results, hemoglobin, creatinine, and brain natriuretic peptide). The decision aid's c-statistic in predicting any 30-day adverse event was 0.7 (95% confidence interval 0.65, 0.76). In conclusion, in patients with AF in the ED, Atrial Fibrillation and Flutter Outcome Risk Determination provides the first evidence-based decision aid for identifying patients who are at low risk for 30-day adverse events and candidates for safe discharge. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Accelerated fetal growth in early pregnancy and risk of severe large-for-gestational-age and macrosomic infant: a cohort study in a low-risk population.

    Science.gov (United States)

    Simic, Marija; Wikström, Anna-Karin; Stephansson, Olof

    2017-10-01

    Our objective was to examine the association between fetal growth in early pregnancy and risk of severe large-for-gestational-age (LGA) and macrosomia at birth in a low-risk population. Cohort study that included 68 771 women with non-anomalous singleton pregnancies, without history of diabetes or hypertension, based on an electronic database on pregnancies and deliveries in Stockholm-Gotland Region, Sweden, 2008-2014. We performed multivariable logistic regression to estimate the association between accelerated fetal growth occurring in the first through early second trimester as measured by ultrasound and LGA and macrosomia at birth. Restricted analyses were performed in the groups without gestational diabetes and with normal body mass index (18.5-24.9 kg/m 2 ). When adjusting for confounders, the odds of having a severely LGA or macrosomic infant were elevated in mothers with fetuses that were at least 7 days larger than expected as compared with mothers without age discrepancy at the second-trimester scan (adjusted odds ratio 1.80; 95% CI 1.23-2.64 and adjusted odds ratio 2.15; 95% CI 1.55-2.98, respectively). Additionally, mothers without gestational diabetes and mothers with normal weight had an elevated risk of having a severely LGA or macrosomic infant when the age discrepancy by second-trimester ultrasound was at least 7 days. In a low-risk population, ultrasound-estimated accelerated fetal growth in early pregnancy was associated with an increased risk of having a severely LGA or macrosomic infant. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  18. Radical parametrectomy after 'cut-through' hysterectomy in low-risk early-stage cervical cancer: Time to consider this procedure obsolete.

    Science.gov (United States)

    Pareja, Rene; Echeverri, Lina; Rendon, Gabriel; Munsell, Mark; Gonzalez-Comadran, Mireia; Sanabria, Daniel; Isla, David; Frumovitz, Michael; Ramirez, Pedro T

    2018-03-01

    The goal of this study is to identify predictive factors in patients with a diagnosis of early-stage cervical cancer after simple hysterectomy in order to avoid a radical parametrectomy. A retrospective review was performed of all patients who underwent radical parametrectomy and bilateral pelvic lymphadenectomy at MD Anderson Cancer Center and at the Instituto de Cancerologia Las Americas in Medellin, Colombia from December 1999 to September 2017. We sought to determine the outcomes in patients diagnosed with low-risk factors (squamous, adenocarcinoma or adenosquamous lesions<2cm in size, and invading<10mm) undergoing radical parametrectomy and pelvic lymphadenectomy. A total of 30 patients were included in the study. The median age was 40.4years (range; 26-60) and median body mass index (BMI) was 26.4kg/m 2 (range; 17.7-40.0). A total 22 patients had tumors<1cm and 8 had tumors between 1 and 2cm. A total of 6 (33%) of 18 patients had evidence of lymph-vascular invasion (LVSI). No radical parametrectomy specimen had residual tumor, involvement of the parametrium, vaginal margin positivity, or lymph node metastasis. None of the patients received adjuvant therapy. After a median follow-up of 99months (range; 6-160) only one patient recurred. Radical parametrectomy may be avoided in patients with low-risk early-stage cervical cancer detected after a simple hysterectomy. Rates of residual disease (parametrial or vaginal) and the need for adjuvant treatments or recurrences are very low. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Outcomes associated with planned home and planned hospital births in low-risk women attended by midwives in Ontario, Canada, 2003-2006: a retrospective cohort study.

    Science.gov (United States)

    Hutton, Eileen K; Reitsma, Angela H; Kaufman, Karyn

    2009-09-01

    Midwives in Ontario, Canada, provide care in the home and hospital and are required to submit data for all births to the Ontario Ministry of Health database. The purpose of this study was to compare maternal and perinatal/neonatal mortality and morbidity and intrapartum intervention rates for women attended by Ontario midwives who planned a home birth compared with similar low-risk women who planned a hospital birth between 2003 and 2006. The database provided outcomes for all women planning a home birth at the onset of labor (n = 6,692) and for a cohort, stratified by parity, of similar low-risk women planning a hospital birth. The rate of perinatal and neonatal mortality was very low (1/1,000) for both groups, and no difference was shown between groups in perinatal and neonatal mortality or serious morbidity (2.4% vs 2.8%; relative risk [RR], 95% confidence intervals [CI]: 0.84 [0.68-1.03]). No maternal deaths were reported. All measures of serious maternal morbidity were lower in the planned home birth group as were rates for all interventions including cesarean section (5.2% vs 8.1%; RR [95% CI]: 0.64 [0.56, 0.73]). Nulliparas were less likely to deliver at home, and had higher rates of ambulance transport from home to hospital than multiparas planning home birth and had rates of intervention and outcomes similar to, or lower than, nulliparas planning hospital births. Midwives who were integrated into the health care system with good access to emergency services, consultation, and transfer of care provided care resulting in favorable outcomes for women planning both home or hospital births.

  20. Development of fine motor skills is associated with expressive language outcomes in infants at high and low risk for autism spectrum disorder.

    Science.gov (United States)

    Choi, Boin; Leech, Kathryn A; Tager-Flusberg, Helen; Nelson, Charles A

    2018-04-12

    A growing body of research suggests that fine motor abilities are associated with skills in a variety of domains in both typical and atypical development. In this study, we investigated developmental trajectories of fine motor skills between 6 and 24 months in relation to expressive language outcomes at 36 months in infants at high and low familial risk for autism spectrum disorder (ASD). Participants included 71 high-risk infants without ASD diagnoses, 30 high-risk infants later diagnosed with ASD, and 69 low-risk infants without ASD diagnoses. As part of a prospective, longitudinal study, fine motor skills were assessed at 6, 12, 18, and 24 months of age and expressive language outcomes at 36 months using the Mullen Scales of Early Learning. Diagnosis of ASD was determined at the infant's last visit to the lab (18, 24, or 36 months) using the Autism Diagnostic Observation Schedule. Hierarchical linear modeling revealed that high-risk infants who later developed ASD showed significantly slower growth in fine motor skills between 6 and 24 months, compared to their typically developing peers. In contrast to group differences in growth from age 6 months, cross-sectional group differences emerged only in the second year of life. Also, fine motor skills at 6 months predicted expressive language outcomes at 3 years of age. These results highlight the importance of utilizing longitudinal approaches in measuring early fine motor skills to reveal subtle group differences in infancy between ASD high-risk and low-risk infant populations and to predict their subsequent language outcomes.

  1. Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature

    International Nuclear Information System (INIS)

    Corso, Giovanni; Marrelli, Daniele; Pascale, Valeria; Vindigni, Carla; Roviello, Franco

    2012-01-01

    The frequency of E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has not been well established. The goal of this study was to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from low- and high-risk areas. English articles using MEDLINE access (from 1998 to 2011). Search terms included CDH1, E-cadherin, germline mutation, gastric cancer, hereditary, familial and diffuse histotype. The study included all E-cadherin germline mutations identified in gastric cancer patients; somatic mutations and germline mutations reported in other tumors were excluded. The method of this study was scheduled in accordance with the 'PRISMA statement for reporting systematic reviews and meta-analyses'. Countries were classified as low- or middle/high risk-areas for gastric carcinoma incidence. Statistical analysis was performed to correlate the CDH1 mutation frequency with gastric cancer incidence areas. A total of 122 E-cadherin germline mutations have been identified; the majority (87.5%) occurred in gastric cancers coming from low-risk areas. In high-risk areas, we identified 16 mutations in which missense mutations were predominant. (68.8%). We verified a significant association between the mutation frequency and the gastric cancer risk area (p < 0.001: overall identified mutations in low- vs. middle/high-risk areas). E-cadherin genetic screenings performed in low-risk areas for gastric cancer identified a higher frequency of CDH1 germline mutations. This data could open new approaches in the gastric cancer prevention test; before proposing a proband candidate for the CDH1 genetic screening, geographic variability, alongside the family history should be considered

  2. Home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban. Rationale and design of the HoT-PE Trial.

    Science.gov (United States)

    Barco, Stefano; Lankeit, Mareike; Binder, Harald; Schellong, Sebastian; Christ, Michael; Beyer-Westendorf, Jan; Duerschmied, Daniel; Bauersachs, Rupert; Empen, Klaus; Held, Matthias; Schwaiblmair, Martin; Fonseca, Cândida; Jiménez, David; Becattini, Cecilia; Quitzau, Kurt; Konstantinides, Stavros

    2016-07-04

    Pulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligible if they meet none of the exclusion criteria indicating haemodynamic instability, serious comorbidity or any condition mandating hospitalisation, or a familial/social environment unable to support home treatment. The first dose of rivaroxaban is given in hospital, and patients are discharged within 48 hours of presentation. Rivaroxaban is taken for at least three months. The primary outcome is symptomatic recurrent venous thromboembolism or PE-related death within three months of enrolment. Secondary outcomes include quality of life and patient satisfaction, and health care resource utilisation compared to existing data on standard-duration hospital treatment. HoT-PE is planned to analyse 1,050 enrolled patients, providing 80 % power to reject the null hypothesis that the recurrence rate of venous thromboembolism is >3 % with α≤0.05. If the hypothesis of HoT-PE is confirmed, early discharge and out-of-hospital treatment may become an attractive, potentially cost-saving option for a significant proportion of patients with acute PE.

  3. Flavonoids as Inhibitors of Human Butyrylcholinesterase Variants

    Directory of Open Access Journals (Sweden)

    Maja Katalinić

    2014-01-01

    Full Text Available The inhibition of butyrylcholinesterase (BChE, EC 3.1.1.8 appears to be of interest in treating diseases with symptoms of reduced neurotransmitter levels, such as Alzheimer’s disease. However, BCHE gene polymorphism should not be neglected in research since it could have an effect on the expected outcome. Several well-known cholinergic drugs (e.g. galantamine, huperzine and rivastigmine originating from plants, or synthesised as derivatives of plant compounds, have shown that herbs could serve as a source of novel target-directed compounds. We focused our research on flavonoids, biologically active polyphenolic compounds found in many plants and plant-derived products, as BChE inhibitors. All of the tested flavonoids: galangin, quercetin, fisetin and luteolin reversibly inhibited usual, atypical, and fluoride-resistant variants of human BChE. The inhibition potency increased in the following order, identically for all three BChE variants: luteolin

  4. Dataset of mitochondrial genome variants in oncocytic tumors

    Directory of Open Access Journals (Sweden)

    Lihua Lyu

    2018-04-01

    Full Text Available This dataset presents the mitochondrial genome variants associated with oncocytic tumors. These data were obtained by Sanger sequencing of the whole mitochondrial genomes of oncocytic tumors and the adjacent normal tissues from 32 patients. The mtDNA variants are identified after compared with the revised Cambridge sequence, excluding those defining haplogroups of our patients. The pathogenic prediction for the novel missense variants found in this study was performed with the Mitimpact 2 program.

  5. Differential Expression Profile of ZFX Variants Discriminates Breast Cancer Subtypes

    Science.gov (United States)

    Pourkeramati, Fatemeh; Asadi, Malek Hossein; Shakeri, Shahryar; Farsinejad, Alireza

    2018-05-13

    ZFX is a transcriptional regulator in embryonic stem cells that plays an important role in pluripotency and self-renewal. ZFX is widely expressed in pluripotent stem cells and is down-regulated during differentiation of embryonic stem cells. ZFX has five different variants that encode three different protein isoforms. While several reports have determined the overexpression of ZFX in a variety of somatic cancers, the expression of ZFX-spliced variants in cancer cells is not well-understood. We investigated the expression of ZFX variants in a series of breast cancer tissues and cell lines using quantitative PCR. The expression of ZFX variant 1/3 was higher in tumor tissue compared to marginal tissue. In contrast, the ZFX variant 5 was down-regulated in tumor tissues. While the ZFX variant 1/3 and ZFX variant 5 expression significantly increased in low-grade tumors, ZFX variant 4 was strongly expressed in high-grade tumors and demonstrating lymphatic invasion. In addition, our result revealed a significant association between the HER2 status and the expression of ZFX-spliced variants. Our data suggest that the expression of ZFX-spliced transcripts varies between different types of breast cancer and may contribute to their tumorigenesis process. Hence, ZFX-spliced transcripts could be considered as novel tumor markers with a probable value in diagnosis, prognosis, and therapy of breast cancer.

  6. Population structure analysis using rare and common functional variants

    Directory of Open Access Journals (Sweden)

    Ding Lili

    2011-11-01

    Full Text Available Abstract Next-generation sequencing technologies now make it possible to genotype and measure hundreds of thousands of rare genetic variations in individuals across the genome. Characterization of high-density genetic variation facilitates control of population genetic structure on a finer scale before large-scale genotyping in disease genetics studies. Population structure is a well-known, prevalent, and important factor in common variant genetic studies, but its relevance in rare variants is unclear. We perform an extensive population structure analysis using common and rare functional variants from the Genetic Analysis Workshop 17 mini-exome sequence. The analysis based on common functional variants required 388 principal components to account for 90% of the variation in population structure. However, an analysis based on rare variants required 532 significant principal components to account for similar levels of variation. Using rare variants, we detected fine-scale substructure beyond the population structure identified using common functional variants. Our results show that the level of population structure embedded in rare variant data is different from the level embedded in common variant data and that correcting for population structure is only as good as the level one wishes to correct.

  7. Human papillomavirus variants among Inuit women in northern Quebec, Canada.

    Science.gov (United States)

    Gauthier, Barbara; Coutlée, Francois; Franco, Eduardo L; Brassard, Paul

    2015-01-01

    Inuit communities in northern Quebec have high rates of human papillomavirus (HPV) infection, cervical cancer and cervical cancer-related mortality as compared to the Canadian population. HPV types can be further classified as intratypic variants based on the extent of homology in their nucleotide sequences. There is limited information on the distribution of intratypic variants in circumpolar areas. Our goal was to describe the HPV intratypic variants and associated baseline characteristics. We collected cervical cell samples in 2002-2006 from 676 Inuit women between the ages of 15 and 69 years in Nunavik. DNA isolates from high-risk HPVs were sequenced to determine the intratypic variant. There were 149 women that were positive for HPVs 16, 18, 31, 33, 35, 45, 52, 56 or 58 during follow-up. There were 5 different HPV16 variants, all of European lineage, among the 57 women positive for this type. There were 8 different variants of HPV18 present and all were of European lineage (n=21). The majority of samples of HPV31 (n=52) were of lineage B. The number of isolates and diversity of the other HPV types was low. Age was the only covariate associated with HPV16 variant category. These frequencies are similar to what was seen in another circumpolar region of Canada, although there appears to be less diversity as only European variants were detected. This study shows that most variants were clustered in one lineage for each HPV type.

  8. Determination of uranium by luminescent method (tablet variant)

    International Nuclear Information System (INIS)

    Sergeev, A.N.; Yufa, B.Ya.

    1985-01-01

    A new tablet variant of luminescent determination of uranium in rocks is developed. The analytical process includes the following operations: sample decomposition, uranium separation from luminescence quencher impurities, preparation of luminescent sample (tablet), photometry of the tablet. The method has two variants developed: the first one is characterized by a more hard decomposition, sample mass being 0.2 g; the second variant has a better detection limit (5x10 -6 %), the sample mass being 0.2-1 g. Procedures of the sample preparation for both variants of analysis are described

  9. Superior and inferior vena cavae: Embryology, variants, and pathology

    International Nuclear Information System (INIS)

    Mendelson, D.S.; Mitty, H.; Janus, C.; Gendal, E.; Berson, B.

    1987-01-01

    The superior and inferior venae cavae may be involved in a host of disease processes. Knowledge of the normal anatomy and variants of these structures is valuable in interpreting plain films and the results of angiographic procedures and all cross-sectional modalities. The authors review the embryology of venae cavae and proceed to describe their normal anatomy and variants. An awareness of the variants can prevent mistaking variants for pathologic processes. Finally, the authors describe pathology involving these vessels and demonstrate the radiographic manifestations

  10. A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant.

    Science.gov (United States)

    Mesquita, Leonardo Pereira; Gamon, Thais Helena Martins; Cuevas, Silvia Elena Campusano; Asano, Karen Miyuki; Fahl, Willian de Oliveira; Iamamoto, Keila; Scheffer, Karin Correa; Achkar, Samira Maria; Zanatto, Dennis Albert; Mori, Cláudia Madalena Cabrera; Maiorka, Paulo César; Mori, Enio

    2017-12-01

    Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD 50 ) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.

  11. Sentinel lymph node biopsy is unsuitable for routine practice in younger female patients with unilateral low-risk papillary thyroid carcinoma

    International Nuclear Information System (INIS)

    Huang, Ou; Xiang, YouQun; Yang, Kai; Zhou, ShuMei; Chen, XueMin; Pan, YiFei; Guo, GuiLong; Zhang, XiaoHua; Wu, WeiLi; Wang, OuChen; You, Jie; Li, Quan; Huang, DuPing; Hu, XiaoQu; Qu, JinMiao; Jin, Cun

    2011-01-01

    Sentinel lymph node (SLN) biopsy has been used to assess patients with papillary thyroid carcinoma (PTC). To achieve its full potential the rate of SLN identification must be as close to 100 percent as possible. In the present study we compared the combination of preoperative lymphoscintigraphy scanning by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery, and methylene blue with methylene blue, alone, for sentinel node identification in younger women with unilateral low-risk PTC. From January 2004 to January 2007, 90 female patients, ages 23 to 44 (mean = 35), with unilateral low-risk PTC (T 1-2 N 0 M 0 ) were prospectively studied. Mean tumor size was 1.3 cm (range, 0.8-3.7 cm). All patients underwent unilateral modified neck dissection. Prior to surgery, patients had, by random assignment, identification and biopsy of SLNs by methylene blue, alone (Group 1), or by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery and methylene blue (Group 2). In the methylene blue group, SLNs were identified in 39 of 45 patients (86.7%). Of the 39 patients, 28 (71.8%) had positive cervical lymph nodes (pN+), and 21 patients (53.8%) had pSLN+. In 7 of the 28 pN+ patients (25%), metastases were also detected in non-SLN, thus giving a false-negative rate (FNR of 38.9% (7/18), a negative predictive value (NPV) of 61.1% (11/18), and an accuracy of 82.1% (32/39). In the combined technique group, the identification rate (IR) of SLN was 100% (45/45). Of the 45 patients, 27 (60.0%) had pN+, 24 (53.3%) had pSLN+. There was a FNR of 14.3% (3/21), a NPV of 85.7% (18/21), and an accuracy of 93.3% (42/45). The combined techniques group was significantly superior to the methylene blue group in IR (p = 0.035). There were no significant differences between two groups in sensitivity, specificity, NPV, or accuracy. Location of pN+ (55 patients) in 84 patients was: level I and V, no patients; level II, 1 patient (1.2%); level III, 6 patients (7.2%); level

  12. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial.

    Science.gov (United States)

    Vora, Ajay; Goulden, Nick; Wade, Rachel; Mitchell, Chris; Hancock, Jeremy; Hough, Rachael; Rowntree, Clare; Richards, Sue

    2013-03-01

    Minimal residual disease (MRD) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukaemia (ALL) during remission. We assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification. Between Oct 1, 2003 and June 30, 2011, consecutive children and young adults (aged 1-25 years) with ALL from the UK and Ireland were recruited. Eligible patients were categorised into clinical standard, intermediate, and high risk groups on the basis of a combination of National Cancer Institute (NCI) criteria, cytogenetics, and early response to induction therapy, which was assessed by bone marrow blast counts taken at days 8 (NCI high-risk patients) and 15 (NCI standard-risk patients) after induction began. Clinical standard-risk and intermediate-risk patients were assessed for MRD. Those classified as MRD low risk (undetectable MRD at the end of induction [day 29] or detectable MRD at day 29 that became undetectable by week 11) were randomly assigned to receive one or two delayed intensification courses. Patients had received induction, consolidation, and interim maintenance therapy before they began delayed intensification. Delayed intensification consisted of pegylated asparaginase on day 4; vincristine, dexamethasone (alternate weeks), and doxorubicin for 3 weeks; and 4 weeks of cyclophosphamide and cytarabine. Computer randomisation was done with stratification by MRD result and balancing for sex, age, and white blood cell count at diagnosis by method of minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcome was event-free survival (EFS), which was defined as time to relapse, secondary tumour, or death. Our aim was to rule out a 7% reduction in EFS in the group given one delayed intensification course relative to that given two delayed intensification courses. Analyses were by intention to treat. This trial is

  13. Variant facial artery in the submandibular region.

    Science.gov (United States)

    Vadgaonkar, Rajanigandha; Rai, Rajalakshmi; Prabhu, Latha V; Bv, Murlimanju; Samapriya, Neha

    2012-07-01

    Facial artery has been considered to be the most important vascular pedicle in facial rejuvenation procedures and submandibular gland (SMG) resection. It usually arises from the external carotid artery and passes from the carotid to digastric triangle, deep to the posterior belly of digastric muscle, and lodges in a groove at the posterior end of the SMG. It then passes between SMG and the mandible to reach the face after winding around the base of the mandible. During a routine dissection, in a 62-year-old female cadaver, in Kasturba Medical College Mangalore, an unusual pattern in the cervical course of facial artery was revealed. The right facial artery was found to pierce the whole substance of the SMG before winding around the lower border of the mandible to enter the facial region. Awareness of existence of such a variant and its comparison to the normal anatomy will be useful to oral and maxillofacial surgeons.

  14. Fast Ordered Sampling of DNA Sequence Variants

    Directory of Open Access Journals (Sweden)

    Anthony J. Greenberg

    2018-05-01

    Full Text Available Explosive growth in the amount of genomic data is matched by increasing power of consumer-grade computers. Even applications that require powerful servers can be quickly tested on desktop or laptop machines if we can generate representative samples from large data sets. I describe a fast and memory-efficient implementation of an on-line sampling method developed for tape drives 30 years ago. Focusing on genotype files, I test the performance of this technique on modern solid-state and spinning hard drives, and show that it performs well compared to a simple sampling scheme. I illustrate its utility by developing a method to quickly estimate genome-wide patterns of linkage disequilibrium (LD decay with distance. I provide open-source software that samples loci from several variant format files, a separate program that performs LD decay estimates, and a C++ library that lets developers incorporate these methods into their own projects.

  15. Fast Ordered Sampling of DNA Sequence Variants.

    Science.gov (United States)

    Greenberg, Anthony J

    2018-05-04

    Explosive growth in the amount of genomic data is matched by increasing power of consumer-grade computers. Even applications that require powerful servers can be quickly tested on desktop or laptop machines if we can generate representative samples from large data sets. I describe a fast and memory-efficient implementation of an on-line sampling method developed for tape drives 30 years ago. Focusing on genotype files, I test the performance of this technique on modern solid-state and spinning hard drives, and show that it performs well compared to a simple sampling scheme. I illustrate its utility by developing a method to quickly estimate genome-wide patterns of linkage disequilibrium (LD) decay with distance. I provide open-source software that samples loci from several variant format files, a separate program that performs LD decay estimates, and a C++ library that lets developers incorporate these methods into their own projects. Copyright © 2018 Greenberg.

  16. Genetic variants in periodontal health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Dumitrescu, Alexandrina L [Tromsoe Univ. (Norway). Inst. of Clinical Dentistry; Kobayashi, Junya [Kyoto Univ. (Japan). Dept. of Genome Repair Dynamics

    2010-07-01

    Periodontitis is a complex, multifactorial disease and its susceptibility is genetically determined. The present book systematically reviews the evidence of the association between the genetic variants and periodontitis progression and/or treatment outcomes. Genetic syndromes known to be associated with periodontal disease, the candidate gene polymorphisms investigated in relation to periodontitis, the heritability of chronic and aggressive periodontitis, as well as common guidelines for association studies are described. This growing understanding of the role of genetic variation in inflammation and periodontal chronic disease presents opportunities to identify healthy persons who are at increased risk of disease and to potentially modify the trajectory of disease to prolong healthy aging. The book represents a new concept in periodontology with its pronounced focus on understanding through knowledge rather than presenting the presently valid answers. Connections between genetics and periodontology are systematically reviewed and covered in detail. (orig.)

  17. Life-time risk of mortality due to different levels of alcohol consumption in seven European countries: implications for low-risk drinking guidelines.

    Science.gov (United States)

    Shield, Kevin D; Gmel, Gerrit; Gmel, Gerhard; Mäkelä, Pia; Probst, Charlotte; Room, Robin; Rehm, Jürgen

    2017-09-01

    Low-risk alcohol drinking guidelines require a scientific basis that extends beyond individual or group judgements of risk. Life-time mortality risks, judged against established thresholds for acceptable risk, may provide such a basis for guidelines. Therefore, the aim of this study was to estimate alcohol mortality risks for seven European countries based on different average daily alcohol consumption amounts. The maximum acceptable voluntary premature mortality risk was determined to be one in 1000, with sensitivity analyses of one in 100. Life-time mortality risks for different alcohol consumption levels were estimated by combining disease-specific relative risk and mortality data for seven European countries with different drinking patterns (Estonia, Finland, Germany, Hungary, Ireland, Italy and Poland). Alcohol consumption data were obtained from the Global Information System on Alcohol and Health, relative risk data from meta-analyses and mortality information from the World Health Organization. The variation in the life-time mortality risk at drinking levels relevant for setting guidelines was less than that observed at high drinking levels. In Europe, the percentage of adults consuming above a risk threshold of one in 1000 ranged from 20.6 to 32.9% for women and from 35.4 to 54.0% for men. Life-time risk of premature mortality under current guideline maximums ranged from 2.5 to 44.8 deaths per 1000 women in Finland and Estonia, respectively, and from 2.9 to 35.8 deaths per 1000 men in Finland and Estonia, respectively. If based upon an acceptable risk of one in 1000, guideline maximums for Europe should be 8-10 g/day for women and 15-20 g/day for men. If low-risk alcohol guidelines were based on an acceptable risk of one in 1000 premature deaths, then maximums for Europe should be 8-10 g/day for women and 15-20 g/day for men, and some of the current European guidelines would require downward revision. © 2017 Society for the Study of Addiction.

  18. Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial.

    Science.gov (United States)

    Freund, Yonathan; Cachanado, Marine; Aubry, Adeline; Orsini, Charlotte; Raynal, Pierre-Alexis; Féral-Pierssens, Anne-Laure; Charpentier, Sandrine; Dumas, Florence; Baarir, Nacera; Truchot, Jennifer; Desmettre, Thibaut; Tazarourte, Karim; Beaune, Sebastien; Leleu, Agathe; Khellaf, Mehdi; Wargon, Mathias; Bloom, Ben; Rousseau, Alexandra; Simon, Tabassome; Riou, Bruno

    2018-02-13

    The safety of the pulmonary embolism rule-out criteria (PERC), an 8-item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has not been assessed in a randomized clinical trial. To prospectively validate the safety of a PERC-based strategy to rule out PE. A crossover cluster-randomized clinical noninferiority trial in 14 emergency departments in France. Patients with a low gestalt clinical probability of PE were included from August 2015 to September 2016, and followed up until December 2016. Each center was randomized for the sequence of intervention periods. In the PERC period, the diagnosis of PE was excluded with no further testing if all 8 items of the PERC rule were negative. The primary end point was the occurrence of a thromboembolic event during the 3-month follow-up period that was not initially diagnosed. The noninferiority margin was set at 1.5%. Secondary end points included the rate of computed tomographic pulmonary angiography (CTPA), median length of stay in the emergency department, and rate of hospital admission. Among 1916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962 were assigned to the PERC group and 954 were assigned to the control group. A total of 1749 patients completed the trial. A PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC group (difference, 1.3% [95% CI, -0.1% to 2.7%]; P = .052). One PE (0.1%) was diagnosed during follow-up in the PERC group vs none in the control group (difference, 0.1% [95% CI, -∞ to 0.8%]). The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, -10% [95% CI, -13% to -6%]; P < .001). In the PERC group, rates were significantly reduced for the median length of emergency department stay (mean reduction, 36 minutes [95% CI, 4 to 68]) and hospital admission (difference, 3.3% [95% CI, 0.1% to 6.6%]). Among very low-risk patients with suspected

  19. OBSTETRIC AND PERINATAL OUTCOME OF LOW-RISK PREGNANCIES WITH TERM LABOUR AND MECONIUM-STAINED AMNIOTIC FLUID AT ST. PHILOMENA’S HOSPITAL

    Directory of Open Access Journals (Sweden)

    Roopashree D

    2016-12-01

    Full Text Available BACKGROUND Meconium-stained amniotic fluid has been considered as sign of foetal distress in presentations other than breech and is associated with poor foetal outcome, but others consider meconium passage by foetus as physiological phenomenon and procedures of environmental hazards to foetus before birth. MATERIALS AND METHODS 200 women with meconium-stained amniotic fluid in labour, all low-risk pregnancies were included in our study from September 2010 to August 2012 admitted in our department. For uniformity of results, cases with obstetric and medical complications were excluded. The cases were divided into three groups depending upon grades of meconium staining as thin, moderate and thick. Foetal monitoring, uterine contractions and Apgar score, birth weight, resuscitation of baby noted. All babies were followed up to first week of neonatal life. RESULTS Of 200 cases, 147 had caesarean delivery 73.5% and 53 had vaginal delivery 26.5%. The incidence of LSCS was found to be maximum in the thick MSAF group 54.5%, 14% in moderate and 5% in this MSAF group. In moderate MSAF group, 2.17% had <7, 1 minute Apgar. In thick MSAF group, 3.33% had <7 Apgar; in thin MSAF group, 11.76% had <7 Apgar at 1 minute. The p value was 0.094 in all grades of MSAF, the 5 min. Apgar’s were more than 7. The occurrence of complications in the baby did not depend on the mode of delivery. The p value was 0.58, which was insignificant. The ‘p value of association of CTG abnormality and foetal morbidity was significant <0.001. The association of grades of meconium and foetal morbidity, the p value was 0.337, which was insignificant. There was no perinatal mortality in our study. CONCLUSION The incidence of low-risk pregnancies with MSAF in our study was 4.5%. There was increased tendency for LSCS in the MSAF. The foetal morbidity depends on the reactivity to CTG not on grades of MSAF. Therefore, close intrapartum monitoring has to be done in such cases and LSCS done

  20. Effect of planned place of birth on obstetric interventions and maternal outcomes among low-risk women: a cohort study in the Netherlands.

    Science.gov (United States)

    Bolten, N; de Jonge, A; Zwagerman, E; Zwagerman, P; Klomp, T; Zwart, J J; Geerts, C C

    2016-10-28

    The use of interventions in childbirth has increased the past decades. There is concern that some women might receive more interventions than they really need. For low-risk women, midwife-led birth settings may be of importance as a counterbalance towards the increasing rate of interventions. The effect of planned place of birth on interventions in the Netherlands is not yet clear. This study aims to give insight into differences in obstetric interventions and maternal outcomes for planned home versus planned hospital birth among women in midwife-led care. Women from twenty practices across the Netherlands were included in 2009 and 2010. Of these, 3495 were low-risk and in midwife-led care at the onset of labour. Information about planned place of birth and outcomes, including instrumental birth (caesarean section, vacuum or forceps birth), labour augmentation, episiotomy, oxytocin in third stage, postpartum haemorrhage >1000 ml and perineal damage, came from the national midwife-led care perinatal database, and a postpartum questionnaire. Women who planned home birth more often had spontaneous birth (nulliparous women aOR 1.38, 95 % CI 1.08-1.76, parous women aOR 2.29, 95 % CI 1.21-4.36) and less often episiotomy (nulliparous women aOR 0.73, 0.58-0.91, parous women aOR 0.47, 0.33-0.68) and use of oxytocin in the third stage (nulliparous women aOR 0.58, 0.42-0.80, parous women aOR 0.47, 0.37-0.60) compared to women who planned hospital birth. Nulliparous women more often had anal sphincter damage (aOR 1.75, 1.01-3.03), but the difference was not statistically significant if women who had caesarean sections were excluded. Parous women less often had labour augmentation (aOR 0.55, 0.36-0.82) and more often an intact perineum (aOR 1.65, 1.34-2.03). There were no differences in rates of vacuum/forceps birth, unplanned caesarean section and postpartum haemorrhage >1000 ml. Women who planned home birth were more likely to give birth spontaneously and had fewer

  1. Utilizing time-driven activity-based costing to understand the short- and long-term costs of treating localized, low-risk prostate cancer.

    Science.gov (United States)

    Laviana, Aaron A; Ilg, Annette M; Veruttipong, Darlene; Tan, Hung-Jui; Burke, Michael A; Niedzwiecki, Douglas R; Kupelian, Patrick A; King, Chris R; Steinberg, Michael L; Kundavaram, Chandan R; Kamrava, Mitchell; Kaplan, Alan L; Moriarity, Andrew K; Hsu, William; Margolis, Daniel J A; Hu, Jim C; Saigal, Christopher S

    2016-02-01

    Given the costs of delivering care for men with prostate cancer remain poorly described, this article reports the results of time-driven activity-based costing (TDABC) for competing treatments of low-risk prostate cancer. Process maps were developed for each phase of care from the initial urologic visit through 12 years of follow-up for robotic-assisted laparoscopic prostatectomy (RALP), cryotherapy, high-dose rate (HDR) and low-dose rate (LDR) brachytherapy, intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and active surveillance (AS). The last modality incorporated both traditional transrectal ultrasound (TRUS) biopsy and multiparametric-MRI/TRUS fusion biopsy. The costs of materials, equipment, personnel, and space were calculated per unit of time and based on the relative proportion of capacity used. TDABC for each treatment was defined as the sum of its resources. Substantial cost variation was observed at 5 years, with costs ranging from $7,298 for AS to $23,565 for IMRT, and they remained consistent through 12 years of follow-up. LDR brachytherapy ($8,978) was notably cheaper than HDR brachytherapy ($11,448), and SBRT ($11,665) was notably cheaper than IMRT, with the cost savings attributable to shorter procedure times and fewer visits required for treatment. Both equipment costs and an inpatient stay ($2,306) contributed to the high cost of RALP ($16,946). Cryotherapy ($11,215) was more costly than LDR brachytherapy, largely because of increased single-use equipment costs ($6,292 vs $1,921). AS reached cost equivalence with LDR brachytherapy after 7 years of follow-up. The use of TDABC is feasible for analyzing cancer services and provides insights into cost-reduction tactics in an era focused on emphasizing value. By detailing all steps from diagnosis and treatment through 12 years of follow-up for low-risk prostate cancer, this study has demonstrated significant cost variation between competing treatments. © 2015

  2. Perinatal and maternal outcomes by planned place of birth for healthy women with low risk pregnancies: the Birthplace in England national prospective cohort study.

    Science.gov (United States)

    Brocklehurst, Peter; Hardy, Pollyanna; Hollowell, Jennifer; Linsell, Louise; Macfarlane, Alison; McCourt, Christine; Marlow, Neil; Miller, Alison; Newburn, Mary; Petrou, Stavros; Puddicombe, David; Redshaw, Maggie; Rowe, Rachel; Sandall, Jane; Silverton, Louise; Stewart, Mary

    2011-11-23

    To compare perinatal outcomes, maternal outcomes, and interventions in labour by planned place of birth at the start of care in labour for women with low risk pregnancies. Prospective cohort study. England: all NHS trusts providing intrapartum care at home, all freestanding midwifery units, all alongside midwifery units (midwife led units on a hospital site with an obstetric unit), and a stratified random sample of obstetric units. 64,538 eligible women with a singleton, term (≥37 weeks gestation), and "booked" pregnancy who gave birth between April 2008 and April 2010. Planned caesarean sections and caesarean sections before the onset of labour and unplanned home births were excluded. A composite primary outcome of perinatal mortality and intrapartum related neonatal morbidities (stillbirth after start of care in labour, early neonatal death, neonatal encephalopathy, meconium aspiration syndrome, brachial plexus injury, fractured humerus, or fractured clavicle) was used to compare outcomes by planned place of birth at the start of care in labour (at home, freestanding midwifery units, alongside midwifery units, and obstetric units). There were 250 primary outcome events and an overall weighted incidence of 4.3 per 1000 births (95% CI 3.3 to 5.5). Overall, there were no significant differences in the adjusted odds of the primary outcome for any of the non-obstetric unit settings compared with obstetric units. For nulliparous women, the odds of the primary outcome were higher for planned home births (adjusted odds ratio 1.75, 95% CI 1.07 to 2.86) but not for either midwifery unit setting. For multiparous women, there were no significant differences in the incidence of the primary outcome by planned place of birth. Interventions during labour were substantially lower in all non-obstetric unit settings. Transfers from non-obstetric unit settings were more frequent for nulliparous women (36% to 45%) than for multiparous women (9% to 13%). The results support a policy

  3. Performance of highly sensitive cardiac troponin T assay to detect ischaemia at PET-CT in low-risk patients with acute coronary syndrome: a prospective observational study.

    Science.gov (United States)

    Morawiec, Beata; Fournier, Stephane; Tapponnier, Maxime; Prior, John O; Monney, Pierre; Dunet, Vincent; Lauriers, Nathalie; Recordon, Frederique; Trana, Catalina; Iglesias, Juan-Fernando; Kawecki, Damian; Boulat, Olivier; Bardy, Daniel; Lamsidri, Sabine; Eeckhout, Eric; Hugli, Olivier; Muller, Olivier

    2017-07-10

    Highly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay's performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented. To assess hs-TnT assay's performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain. Patients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography. Forty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was <4 ng/L. Using this value, sensitivity, specificity, positive and negative predictive values of hs-TnT to predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2 and 100%/43%/20%/100% at T6, respectively. Our findings suggest that in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L demonstrates excellent negative predictive value to exclude myocardial ischaemia detection at PET-CT, at the expense of weak specificity and positive predictive value. ClinicalTrials.gov Identifier: NCT01374607. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly

  4. CT should replace three-view radiographs as the initial screening test in patients at high, moderate, and low risk for blunt cervical spine injury: a prospective comparison.

    Science.gov (United States)

    Bailitz, John; Starr, Frederic; Beecroft, Matthew; Bankoff, Jon; Roberts, Roxanne; Bokhari, Faran; Joseph, Kimberly; Wiley, Dorian; Dennis, Andrew; Gilkey, Susan; Erickson, Paul; Raksin, Patricia; Nagy, Kimberly

    2009-06-01

    An estimated 10,000 Americans suffer cervical spine injuries each year. More than 800,000 cervical spine radiographs (CSR) are ordered annually. The human and healthcare costs associated with these injuries are enormous especially when diagnosis is delayed. Controversy exists in the literature concerning the diagnostic accuracy of CSR, with reported sensitivity ranging from 32% to 89%. We sought to compare prospectively the sensitivity of cervical CT (CCT) to CSR in the initial diagnosis of blunt cervical spine injury for patients meeting one or more of the NEXUS criteria. The study prospectively compared the diagnostic accuracy of CSR to CCT in consecutive patients evaluated for blunt trauma during 23 months at an urban, public teaching hospital and Level I Trauma Center. Inclusion criteria were adult patient, evaluated for blunt cervical spine injury, meeting one or more of the NEXUS criteria. All patients received both three-view CSR and CCT as part of a standard diagnostic protocol. Each CSR and CCT study was interpreted independently by a different radiology attending who was blinded to the results of the other study. Clinically significant injuries were defined as those requiring one or more of the following interventions: operative procedure, halo application, and/or rigid cervical collar. Of 1,583 consecutive patients evaluated for blunt cervical spine trauma, 78 (4.9%) patients received only CCT or CSR and were excluded from the study. Of the remaining 1,505 patients, 78 (4.9%) had evidence of a radiographic injury by CSR or CCT. Of these 78 patients with radiographic injury, 50 (3.3%) patients had clinically significant injuries. CCT detected all patients with clinically significant injuries (100% sensitive), whereas CSR detected only 18 (36% sensitive). Of the 50 patients, 15 were at high risk, 19 at moderate risk, and 16 at low risk for cervical spine injury according to previously published risk stratification. CSR detected clinically significant

  5. Nuclear variants of bone morphogenetic proteins

    Directory of Open Access Journals (Sweden)

    Meinhart Christopher A

    2010-03-01

    Full Text Available Abstract Background Bone morphogenetic proteins (BMPs contribute to many different aspects of development including mesoderm formation, heart development, neurogenesis, skeletal development, and axis formation. They have previously been recognized only as secreted growth factors, but the present study detected Bmp2, Bmp4, and Gdf5/CDMP1 in the nuclei of cultured cells using immunocytochemistry and immunoblotting of nuclear extracts. Results In all three proteins, a bipartite nuclear localization signal (NLS was found to overlap the site at which the proproteins are cleaved to release the mature growth factors from the propeptides. Mutational analyses indicated that the nuclear variants of these three proteins are produced by initiating translation from downstream alternative start codons. The resulting proteins lack N-terminal signal peptides and are therefore translated in the cytoplasm rather than the endoplasmic reticulum, thus avoiding proteolytic processing in the secretory pathway. Instead, the uncleaved proteins (designated nBmp2, nBmp4, and nGdf5 containing the intact NLSs are translocated to the nucleus. Immunostaining of endogenous nBmp2 in cultured cells demonstrated that the amount of nBmp2 as well as its nuclear/cytoplasmic distribution differs between cells that are in M-phase versus other phases of the cell cycle. Conclusions The observation that nBmp2 localization varies throughout the cell cycle, as well as the conservation of a nuclear localization mechanism among three different BMP family members, suggests that these novel nuclear variants of BMP family proteins play an important functional role in the cell.

  6. Characterization of fibroblast growth factor receptor 2 overexpression in the human breast cancer cell line SUM-52PE

    International Nuclear Information System (INIS)

    Tannheimer, Stacey L; Rehemtulla, Alnawaz; Ethier, Stephen P

    2000-01-01

    The fibroblast growth factor receptor (FGFR)2 gene has been shown to be amplified in 5-10% of breast cancer patients. A breast cancer cell line developed in our laboratory, SUM-52PE, was shown to have a 12-fold amplification of the FGFR2 gene, and FGFR2 message was found to be overexpressed 40-fold in SUM-52PE cells as compared with normal human mammary epithelial (HME) cells. Both human breast cancer (HBC) cell lines and HME cells expressed two FGFR2 isoforms, whereas SUM-52PE cells overexpressed those two isoforms, as well as several unique FGFR2 polypeptides. SUM-52PE cells expressed exclusively FGFR2-IIIb isoforms, which are high-affinity receptors for fibroblast growth factor (FGF)-1 and FGF-7. Differences were identified in the expression of the extracellular Ig-like domains, acid box and carboxyl termini, and several variants not previously reported were isolated from these cells. The FGFR family of receptor tyrosine kinases includes four members, all of which are highly alternatively spliced and glycosylated. For FGFR2, alternative splicing of the second half of the third Ig-like domain, involving exons IIIb and IIIc, is a mutually exclusive choice that affects ligand binding specificity and affinity [1,2,3]. It appears that the second half of the third Ig-like domain can dictate high affinity for FGF-2 or keratinocyte growth factor (KGF), whereas affinity for FGF-1 appears to remain the same [3]. Alternative splicing of the carboxyl terminus has been shown to involve at least two different exons that can produce at least three different variants. The C1-type and C2-type carboxyl termini are encoded by the same exon, and have two different splice acceptor sites, whereas the C3-type carboxyl terminus is encoded by a separate exon [4]. The biologic significance of the C1 carboxyl terminus, as compared with the shorter C3 variant found primarily in tumorigenic samples, has been studied in NIH3T3 transfection assays, in which C3 variants were able to produce

  7. Re-Ranking Sequencing Variants in the Post-GWAS Era for Accurate Causal Variant Identification

    Science.gov (United States)

    Faye, Laura L.; Machiela, Mitchell J.; Kraft, Peter; Bull, Shelley B.; Sun, Lei

    2013-01-01

    Next generation sequencing has dramatically increased our ability to localize disease-causing variants by providing base-pair level information at costs increasingly feasible for the large sample sizes required to detect complex-trait associations. Yet, identification of causal variants within an established region of association remains a challenge. Counter-intuitively, certain factors that increase power to detect an associated region can decrease power to localize the causal variant. First, combining GWAS with imputation or low coverage sequencing to achieve the large sample sizes required for high power can have the unintended effect of producing differential genotyping error among SNPs. This tends to bias the relative evidence for association toward better genotyped SNPs. Second, re-use of GWAS data for fine-mapping exploits previous findings to ensure genome-wide significance in GWAS-associated regions. However, using GWAS findings to inform fine-mapping analysis can bias evidence away from the causal SNP toward the tag SNP and SNPs in high LD with the tag. Together these factors can reduce power to localize the causal SNP by more than half. Other strategies commonly employed to increase power to detect association, namely increasing sample size and using higher density genotyping arrays, can, in certain common scenarios, actually exacerbate these effects and further decrease power to localize causal variants. We develop a re-ranking procedure that accounts for these adverse effects and substantially improves the accuracy of causal SNP identification, often doubling the probability that the causal SNP is top-ranked. Application to the NCI BPC3 aggressive prostate cancer GWAS with imputation meta-analysis identified a new top SNP at 2 of 3 associated loci and several additional possible causal SNPs at these loci that may have otherwise been overlooked. This method is simple to implement using R scripts provided on the author's website. PMID:23950724

  8. Genomewide association study identifies no major founder variant in ...

    Indian Academy of Sciences (India)

    2013-12-10

    Dec 10, 2013 ... variant in Caucasian moyamoya disease ... 1Department of Health and Environmental Sciences, Kyoto University Graduate ... a low prevalence in European countries (Goto and Yonekawa. 1992; Kuroda and Houkin 2008). We have found that the p.R4810K variant in the ring finger protein 213 (RNF213).

  9. Managing Process Variants in the Process Life Cycle

    NARCIS (Netherlands)

    Hallerbach, A.; Bauer, Th.; Reichert, M.U.

    2007-01-01

    When designing process-aware information systems, often variants of the same process have to be specified. Each variant then constitutes an adjustment of a particular process to specific requirements building the process context. Current Business Process Management (BPM) tools do not adequately

  10. Germline Variants of Prostate Cancer in Japanese Families.

    Directory of Open Access Journals (Sweden)

    Takahide Hayano

    Full Text Available Prostate cancer (PC is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family. We also found shared variants of BRCA2, HOXB13, and TRRAP from 59 additional small PC families (two patients per family. We identified two deleterious HOXB13 variants (F127C and G132E. Further exploration of the shared variants in rest of the families revealed deleterious variants of the so-called cancer genes (ATP1A1, BRIP1, FANCA, FGFR3, FLT3, HOXD11, MUTYH, PDGFRA, SMARCA4, and TCF3. The germline variant profile provides a new insight to clarify the genetic etiology and heterogeneity of PC among Japanese men.

  11. Holographic representation of space-variant systems: system theory.

    Science.gov (United States)

    Marks Ii, R J; Krile, T F

    1976-09-01

    System theory for holographic representation of linear space-variant systems is derived. The utility of the resulting piecewise isoplanatic approximation (PIA) is illustrated by example application to the invariant system, ideal magnifier, and Fourier transformer. A method previously employed to holographically represent a space-variant system, the discrete approximation, is shown to be a special case of the PIA.

  12. Detecting rare variants in case-parents association studies.

    Directory of Open Access Journals (Sweden)

    Kuang-Fu Cheng

    Full Text Available Despite the success of genome-wide association studies (GWASs in detecting common variants (minor allele frequency ≥0.05 many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT, multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

  13. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

    Science.gov (United States)

    2017-10-01

    resistant prostate cancer ; docetaxel; cabazitaxel; chemotherapy; androgen receptor splice variants; microtubule; ligand-binding domain; microtubule... receptor splice variants (AR-Vs) are associated with resistance to taxane chemotherapy in castration- resistant prostate cancer (CRPC). However, this...androgen receptor inhibitors in prostate cancer . Nat Rev Cancer . 2015;15:701–11.

  14. Hepatitis E Virus Variant in Farmed Mink, Denmark

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Breum, Solvej Østergaard; Jensen, Trine Hammer

    2013-01-01

    Hepatitis E virus (HEV) is a zoonotic virus for which pigs are the primary animal reservoir. To investigate whether HEV occurs in mink in Denmark, we screened feces and tissues from domestic and wild mink. Our finding of a novel HEV variant supports previous findings of HEV variants in a variety...

  15. Variant Creutzfeldt-Jakob Disease (vCJD)

    Science.gov (United States)

    ... Form Controls Cancel Submit Search the CDC Variant Creutzfeldt-Jakob Disease (vCJD) Note: Javascript is disabled or is not ... gov . Recommend on Facebook Tweet Share Compartir Variant Creutzfeldt-Jakob disease (vCJD) is a prion disease that was first ...

  16. Genetics Home Reference: GM2-gangliosidosis, AB variant

    Science.gov (United States)

    ... Resources Genetic Testing (1 link) Genetic Testing Registry: Tay-Sachs disease, variant AB General Information from MedlinePlus (5 links) ... AB variant Activator Deficiency/GM2 Gangliosidosis Activator-deficient Tay-Sachs disease GM2 Activator Deficiency Disease GM2 gangliosidosis, type AB ...

  17. Assessment of Functional Effects of Unclassified Genetic Variants

    NARCIS (Netherlands)

    Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels

    2008-01-01

    Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

  18. Assessment of Functional Effects of Unclassified Genetic Variants

    NARCIS (Netherlands)

    Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels

    Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

  19. Association analysis identifies ZNF750 regulatory variants in psoriasis

    Directory of Open Access Journals (Sweden)

    Birnbaum Ramon Y

    2011-12-01

    Full Text Available Abstract Background Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene. Methods We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls. Results We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families. Conclusions Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.

  20. ADULT VARIANT BARTTER’S SYNDROME- A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Ishwar Sidappa Hasabi

    2017-02-01

    Full Text Available BACKGROUND Bartter syndrome is a group of channelopathies with different genetic origins and molecular pathophysiologies, but sharing common feature of decreased tubular transport of sodium chloride in thick ascending loop of Henle (TAL, 1 although more common in antenatal group. Classic adult variant of Bartter syndrome is a rare entity. We hereby present a rare adult variant of classic Bartter syndrome.

  1. Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation

    DEFF Research Database (Denmark)

    Ghoussaini, Maya; French, Juliet D; Michailidou, Kyriaki

    2016-01-01

    expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers......, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis....

  2. Performance of motor sequences in children at heightened vs. low risk for ASD: A longitudinal study from 18 to 36 months of age

    Directory of Open Access Journals (Sweden)

    VALENTINA eFOCAROLI

    2016-05-01

    Full Text Available Recent research shows that motor difficulties are a prominent component of the behavioral profile of autism spectrum disorder (ASD and are also apparent from early in development in infants who have an older sibling with ASD (High Risk; HR. Delays have been reported for HR infants who do and who do not receive an eventual diagnosis of ASD. A growing body of prospective studies has focused on the emergence of early motor skills primarily during the first year of life. To date, however, relatively little work has examined motor skills in the second and third years. Thus, the present research was designed to investigate motor performance in object transport tasks longitudinally in HR and LR (Low Risk children between the ages of 18 and 36 months. Participants (15 HR children and 14 LR children were observed at 18, 24, and 36 months. Children completed two motor tasks, the Ball Task and the Block Task, each of which included two conditions that varied in terms of the precision demands of the goal action. Kinematic data were acquired via two magneto inertial sensors worn on each wrist. In the Block Task, HR children reached more slowly (i.e., mean acceleration was lower compared to LR children. This finding is in line with growing evidence of early delays in fine motor skills in HR children and suggests that vulnerabilities in motor performance may persist into the preschool years in children at risk for ASD.

  3. Prevalence, incidence and correlates of low risk HPV infection and anogenital warts in a cohort of women living with HIV in Burkina Faso and South Africa.

    Science.gov (United States)

    Chikandiwa, Admire; Kelly, Helen; Sawadogo, Bernard; Ngou, Jean; Pisa, Pedro T; Gibson, Lorna; Didelot, Marie-Noelle; Meda, Nicolas; Weiss, Helen A; Segondy, Michel; Mayaud, Philippe; Delany-Moretlwe, Sinead

    2018-01-01

    To report the prevalence and incidence of low-risk human papillomavirus infection (LR-HPV) and anogenital warts (AGW) among women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA), and to explore HIV-related factors associated with these outcomes. We enrolled 1238 WLHIV (BF = 615; SA = 623) aged 25-50 years and followed them at three time points (6, 12 and 16 months) after enrolment. Presence of AGW was assessed during gynaecological examination. Cervico-vaginal swabs for enrolment and month 16 follow-up visits were tested for HPV infection by Inno-LiPA® genotyping. Logistic regression was used to assess risk factors for prevalent infection or AGW. Cox regression was used to assess risk factors for incident AGW. Women in SA were more likely than those in BF to have prevalent LR-HPV infection (BF: 27.1% vs. SA: 40.9%; p500 cells/μL). Duration of ART and HIV plasma viral load were not associated with any LR-HPV infection or AGW outcomes. LR-HPV infection and AGW are common in WLHIV in sub-Saharan Africa. Type-specific HPV vaccines and effective ART with immunological reconstitution could reduce the burden of AGW in this population.

  4. High-risk versus low-risk football game weekends: differences in problem drinking and alcohol-related consequences on college campuses in the United States.

    Science.gov (United States)

    Champion, Heather; Blocker, Jill N; Buettner, Cynthia K; Martin, Barbara A; Parries, Maria; Mccoy, Thomas P; Mitra, Ananda; Andrews, David W; Rhodes, Scott D

    2009-01-01

    Collegiate football games provide multiple social opportunities for alcohol use by students over the course of the weekend. The goal of this study was to examine alcohol use and alcohol-related consequences on football game weekends to determine differences based on characteristics of the game. A random sample of students from two large, public universities in the United States completed a survey on the Sunday-Friday following a high-risk weekend (HRW, important, home game) and low-risk weekend (LRW, no home game or game of importance) (N = 3,238 total). The survey measured the number of days students drank (0-3) and got drunk (0-3) over the weekend and whether 1+ consequences were experienced due to one's own drinking (yes/no) and due to others' drinking (yes/no). Ordinal logistic regression analyses revealed greater odds of drinking alcohol (OR = 1.70, CI = 1.46-1.97) and getting drunk (OR = 1.49, CI = 1.27-1.76) on HRW versus LRW. Logistic regression analyses revealed greater odds of experiencing 1+ consequences as a result of one's own drinking (OR = 1.38, CI = 1.16-1.63) and experiencing 1+ consequences as a result of others' drinking (OR = 1.52, CI = 1.30-1.78) on HRW versus LRW. These findings suggest that additional prevention efforts aimed at reducing risky drinking are needed over HRW and have implications for campus administrators, law enforcement, and substance abuse program coordinators.

  5. Ponderal index (PI) vs birth weight centiles in the low-risk primigravid population: which is the better predictor of fetal wellbeing?

    LENUS (Irish Health Repository)

    Cooley, S M

    2012-07-01

    Our objective was to compare Ponderal index (PI) with birth weight centiles as predictors of perinatal morbidity and to determine which best reflects the presence of placental disease. We prospectively recruited 1,011 low-risk primigravidas and calculated PI and birth weight centiles following delivery. Perinatal morbidity was defined as: pre-term birth (PTB); fetal acidosis; an Apgar score <7 at 5 min or neonatal resuscitation. Placental disease was defined as chronic uteroplacental insufficiency (CUPI); villous dysmaturity; infection or vascular pathology. Ponderal index was statistically reduced (25.33 vs 27.79 p =0.001) and the incidence of infant birth weight <9th centile was statistically higher (11.1% vs 5.1%; p =0.004) in cases with PTB and in CUPI (26.23 vs 27.84; p =0.001 and 28.2.1% vs 10.4%; p =0.002). Both PI and infant birth weight centile <9th centile for gestational age correlate with PTB, however overall, both are poor predictors of neonatal and placental disease.

  6. Normal value of functional parameters in gated myocardial perfusion SPECT in patients with low risk of coronary artery disease: emory cardiac tool box program

    Energy Technology Data Exchange (ETDEWEB)

    Kang, D. Y.; Kim, M. H.; Kim, Y. D.; Kim, D. K. [Donga University College of Medicine, Busan (Korea, Republic of)

    2002-07-01

    Absolute value of the functional data of gated myocardial perfusion SPECT is necessary to determine that individual patient is normal or not. Tc-99m MIBI gated myocardial perfusion SPECT was performed using emory cardiac tool box program. All patients (M:F=15:36, age 64{+-}10 yrs) showed normal myocardial perfusion. The patients with following characteristics were excluded; previous angina or MI, ECG change with Q wave or ST-T change, diabetes mellitus, hypercholesterolemia, typical chest pain and hypertension. In all patients, myocardial mass is 117{+-}23 g in stress gated SPECT, 106{+-}22 g in stress ungated SPECT and 102{+-}21 g in rest ungated SPECT. EDV is 90{+-}28 ml, ESV 26{+-}20 ml, SV 66{+-}21 ml, EF 73{+-}10 % and TID 1.06{+-}0.14. Myocardial mass in rest ungated SPECT is significantly different between men and women (p=0.025). Myocardial mass is significantly different between stress gated SPECT and stress ungated SPECT (p=0.000), and between stress ungated SPECT and rest ungated SPECT (p=0.003). We provide normal value of functional parameters to determine the abnormality of individual patients in patients with low risk of coronary artery disease.

  7. The nuclear localization of low risk HPV11 E7 protein mediated by its zinc binding domain is independent of nuclear import receptors

    International Nuclear Information System (INIS)

    Piccioli, Zachary; McKee, Courtney H.; Leszczynski, Anna; Onder, Zeynep; Hannah, Erin C.; Mamoor, Shahan; Crosby, Lauren; Moroianu, Junona

    2010-01-01

    We investigated the nuclear import of low risk HPV11 E7 protein using 1) transfection assays in HeLa cells with EGFP fusion plasmids containing 11E7 and its domains and 2) nuclear import assays in digitonin-permeabilized HeLa cells with GST fusion proteins containing 11E7 and its domains. The EGFP-11E7 and EGFP-11cE7 39-98 localized mostly to the nucleus. The GST-11E7 and GST-11cE7 39-98 were imported into the nuclei in the presence of either Ran-GDP or RanG19V-GTP mutant and in the absence of nuclear import receptors. This suggests that 11E7 enters the nucleus via a Ran-dependent pathway, independent of nuclear import receptors, mediated by a nuclear localization signal located in its C-terminal domain (cNLS). This cNLS contains the zinc binding domain consisting of two copies of Cys-X-X-Cys motif. Mutagenesis of Cys residues in these motifs changed the localization of the EGFP-11cE7/-11E7 mutants to cytoplasmic, suggesting that the zinc binding domain is essential for nuclear localization of 11E7.

  8. Active surveillance for low-risk prostate cancer in Austria: the online registry of the Qualitätspartnerschaft Urologie (QuapU).

    Science.gov (United States)

    Eredics, Klaus; Dorfinger, Karl; Kramer, Gero; Ponholzer, Anton; Madersbacher, Stephan

    2017-06-01

    Active surveillance (AS) is a well-recognized strategy to reduce the risk of overtreatment in men with low-risk prostate cancer. No data on this approach are available from Austria. The Qualitätspartnerschaft Urologie (QuapU) developed an online database for patients managed with AS in Austria. Principal inclusion/exclusion criteria corresponded to those of the S3 prostate cancer guideline of German urologists: prostate-specific antigen (PSA) 4-10 ng/ml: 85%). The prostate volume averaged 39 ml. The mean time under AS was 17.5 months (12 months: 40%). The AS adherence at 12 months was 85% and at 24 months 76%. To date, a total of 23 patients (17.6%) stopped AS. The most frequent reasons for discontinuing AS were patient wish for active treatment (43.5%) and PSA progression (30.4%). A histological progression was rarely seen (6.1%) and the control biopsy rate was low (19.8%). This study is the first description of AS in Austria and documents the feasibility of an online registry for AS. The data confirm the international experience with this approach with acceptable adherence rates.

  9. The role of a personalized dietary intervention in managing gestational weight gain: a prospective, controlled study in a low-risk antenatal population.

    Science.gov (United States)

    Di Carlo, Costantino; Iannotti, Giuseppina; Sparice, Stefania; Chiacchio, Maria Pia; Greco, Elena; Tommaselli, Giovanni Antonio; Nappi, Carmine

    2014-04-01

    To compare the efficacy of a personal dietary intervention on gestational weight gain control with a general intervention promoting healthy eating. Prospective, controlled study including 154 low-risk pregnant women randomly allocated to two groups: 77 receiving a personalized diet plan and a close follow-up by a dietician (intervention group), 77 receiving standard dietary care by means of a brochure on healthy eating during pregnancy (control group). Pre-pregnancy weight, gestational age, height, weight and BMI at baseline, weight at term, gestational age at delivery and newborn weight were recorded for all participants. The primary end-point was the difference in body weight between baseline and term. Secondary end-points were the difference in body weight between pre-pregnancy and term and in newborn weights. Maternal weight gain at term was significantly lower both as compared to pre-pregnancy weight (8.2 ± 4.0 vs. 13.4 ± 4.2 kg; p weight at baseline (7.7 ± 3.8 vs. 13.7 ± 4.3 kg; p weight between baseline and term and newborn weight was observed in both groups, but stronger in patients from the intervention group (intervention group R = 0.76, p weight gain in pregnant women.

  10. Detection of serous precursor lesions in resected fallopian tubes from patients with benign diseases and a relatively low risk for ovarian cancer.

    Science.gov (United States)

    Nishida, Naoyo; Murakami, Fumihiro; Higaki, Koichi

    2016-06-01

    The frequency of ovarian cancers in Japan has increased; however, doubts have been raised concerning the mechanism by which high-grade serous adenocarcinomas (HGSCs) arise. Conventionally, HGSC is thought to originate from the ovarian surface epithelium or epithelial inclusion cyst. However, recent data indicate that HGSCs may in fact develop from precursor lesions in the fallopian tube, including epithelia with a p53 signature, serous tubal intraepithelial carcinomas (STICs), secretory cell outgrowths (SCOUTs), and tubal intraepithelial lesions in transition (TILT). Here, we determined the frequency of these fallopian tube precursors in surgically excised samples from 123 patients with benign pelvic diseases. We identified 12 cases with a p53 signature (9.7%), 26 with observable SCOUTs (21.1%), and 4 with TILT (3.2%), but no STIC cases. Although the lifetime risk for developing ovarian cancer is only around 1.4% for women without germ-line mutations, it is important to evaluate the presence of precursor lesions to understand HGSC pathogenesis better. Taken together, salpingectomy appears to be an option for women who are past their childbearing age and plan to undergo elective pelvic surgery. To our knowledge, this is the first study to investigate the presence of these specific precursors post-salpingectomy in low-risk patients. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  11. A national standard for psychosocial safety climate (PSC): PSC 41 as the benchmark for low risk of job strain and depressive symptoms.

    Science.gov (United States)

    Bailey, Tessa S; Dollard, Maureen F; Richards, Penny A M

    2015-01-01

    Despite decades of research from around the world now permeating occupational health and safety (OHS) legislation and guidelines, there remains a lack of tools to guide practice. Our main goal was to establish benchmark levels of psychosocial safety climate (PSC) that would signify risk of job strain (jobs with high demands and low control) and depression in organizations. First, to justify our focus on PSC, using interview data from Australian employees matched at 2 time points 12 months apart (n = 1081), we verified PSC as a significant leading predictor of job strain and in turn depression. Next, using 2 additional data sets (n = 2097 and n = 1043) we determined benchmarks of organizational PSC (range 12-60) for low-risk (PSC at 41 or above) and high-risk (PSC at 37 or below) of employee job strain and depressive symptoms. Finally, using the newly created benchmarks we estimated the population attributable risk (PAR) and found that improving PSC in organizations to above 37 could reduce 14% of job strain and 16% of depressive symptoms in the working population. The results provide national standards that organizations and regulatory agencies can utilize to promote safer working environments and lower the risk of harm to employee mental health. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  12. Prevalence, incidence and correlates of low risk HPV infection and anogenital warts in a cohort of women living with HIV in Burkina Faso and South Africa.

    Directory of Open Access Journals (Sweden)

    Admire Chikandiwa

    Full Text Available To report the prevalence and incidence of low-risk human papillomavirus infection (LR-HPV and anogenital warts (AGW among women living with HIV (WLHIV in Burkina Faso (BF and South Africa (SA, and to explore HIV-related factors associated with these outcomes.We enrolled 1238 WLHIV (BF = 615; SA = 623 aged 25-50 years and followed them at three time points (6, 12 and 16 months after enrolment. Presence of AGW was assessed during gynaecological examination. Cervico-vaginal swabs for enrolment and month 16 follow-up visits were tested for HPV infection by Inno-LiPA® genotyping. Logistic regression was used to assess risk factors for prevalent infection or AGW. Cox regression was used to assess risk factors for incident AGW.Women in SA were more likely than those in BF to have prevalent LR-HPV infection (BF: 27.1% vs. SA: 40.9%; p500 cells/μL. Duration of ART and HIV plasma viral load were not associated with any LR-HPV infection or AGW outcomes.LR-HPV infection and AGW are common in WLHIV in sub-Saharan Africa. Type-specific HPV vaccines and effective ART with immunological reconstitution could reduce the burden of AGW in this population.

  13. Late acute humoral rejection in low-risk renal transplant recipients induced with an interleukin-2 receptor antagonist and maintained with standard therapy: preliminary communication.

    Science.gov (United States)

    Morales, J; Contreras, L; Zehnder, C; Pinto, V; Elberg, M; Araneda, S; Herzog, C; Calabran, L; Aguiló, J; Ferrario, M; Buckel, E; Fierro, J A

    2011-01-01

    Low-risk renal transplant recipients treated with standard immunosuppressive therapy including interleukin-2 receptor (IL-2R) antagonist show a low incidence of early rejection episodes but few reports have examined the incidence and severity of late rejection processes. This study evaluated retrospectively cellular and antibody-mediated rejection (AMR) among 42 recipients selected because they showed low panel-reactive-antibodies, short cold ischemia time, no delayed graft function, and therapy including basiliximab (Simulect) induction. The mean observation time was 6.6 years. Sixty-seven percent of donors were deceased. Ten-year patient and death-censored graft survivals were 81% and 78%, respectively. Seven patients lost their kidneys due to nonimmunologic events. The seven recipients who experienced cellular rejection episodes during the first posttransplant year had them reversed with steroids. Five patients displayed late acute AMR causing functional deterioration in four cases including 1 graft loss. De novo sensitization occurred in 48% of recipients including patients without clinical rejection. In conclusion, long-term follow-up of kidney transplant recipients selected by a low immunologic risk showed a persistent risk of de novo sensitization evolving to acute AMR in 11% of cases. Although immunologic events were related to late immunosuppressive reduction, most graft losses were due to nonimmunologic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Combinations of Genetic Variants Occurring Exclusively in Patients

    Directory of Open Access Journals (Sweden)

    Erling Mellerup

    Full Text Available In studies of polygenic disorders, scanning the genetic variants can be used to identify variant combinations. Combinations that are exclusively found in patients can be separated from those combinations occurring in control persons. Statistical analyses can be performed to determine whether the combinations that occur exclusively among patients are significantly associated with the investigated disorder. This research strategy has been applied in materials from various polygenic disorders, identifying clusters of patient-specific genetic variant combinations that are significant associated with the investigated disorders. Combinations from these clusters are found in the genomes of up to 55% of investigated patients, and are not present in the genomes of any control persons. Keywords: Genetic variants, Polygenic disorder, Combinations of genetic variants, Patient-specific combinations

  15. Golden Rule of Morphology and Variants of Word forms

    Directory of Open Access Journals (Sweden)

    Hlaváčová Jaroslava

    2017-12-01

    Full Text Available In many languages, some words can be written in several ways. We call them variants. Values of all their morphological categories are identical, which leads to an identical morphological tag. Together with the identical lemma, we have two or more wordforms with the same morphological description. This ambiguity may cause problems in various NLP applications. There are two types of variants – those affecting the whole paradigm (global variants and those affecting only wordforms sharing some combinations of morphological values (inflectional variants. In the paper, we propose means how to tag all wordforms, including their variants, unambiguously. We call this requirement “Golden rule of morphology”. The paper deals mainly with Czech, but the ideas can be applied to other languages as well.

  16. Electrophoretic variants of blood proteins in Japanese, 7

    International Nuclear Information System (INIS)

    Satoh, Chiyoko; Takahashi, Norio; Kimura, Yasukazu; Miura, Akiko; Kaneko, Junko; Fujita, Mikio; Toyama, Kyoko.

    1986-11-01

    A total of 16,835 children, of whom 11,737 are unrelated, from Hiroshima and Nagasaki were examined for erythrocyte cytoplasmic glutamate-oxaloacetate transaminase (GOT1) by starch gel electrophoresis. A variant allele named GOT1*2HR1 which seems to be identical with GOT1*2 was encountered in polymorphic frequency. Five kinds of rare variants, 3NG1, 4NG1, 5NG1, 6HR1, and 7NG1 were encountered in a total of 109 children. Except for 7NG1 for which complete family study was unable, family studies confirmed the genetic nature of these rare variants, since for all instances in which both parents could be examined, one of the parents exhibited the same variant as that of their child. Thermostability profiles of these six variants were normal. The enzyme activities of five were decreased, while the value of one was normal compared to that of GOT1 1. (author)

  17. Bayesian detection of causal rare variants under posterior consistency.

    KAUST Repository

    Liang, Faming

    2013-07-26

    Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

  18. Bayesian detection of causal rare variants under posterior consistency.

    Directory of Open Access Journals (Sweden)

    Faming Liang

    Full Text Available Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD, to tackle this problem. The new method simultaneously addresses two issues: (i (Global association test Are there any of the variants associated with the disease, and (ii (Causal variant detection Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

  19. Bayesian detection of causal rare variants under posterior consistency.

    KAUST Repository

    Liang, Faming; Xiong, Momiao

    2013-01-01

    Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

  20. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis

    NARCIS (Netherlands)

    Rivas, Manuel A.; Graham, Daniel; Sulem, Patrick; Stevens, Christine; Desch, A. Nicole; Goyette, Philippe; Gudbjartsson, Daniel; Jonsdottir, Ingileif; Thorsteinsdottir, Unnur; Degenhardt, Frauke; Mucha, Soeren; Kurki, Mitja I.; Li, Dalin; D'Amato, Mauro; Annese, Vito; Vermeire, Severine; Weersma, Rinse K.; Halfvarson, Jonas; Paavola-Sakki, Paulina; Lappalainen, Maarit; Lek, Monkol; Cummings, Beryl; Tukiainen, Taru; Haritunians, Talin; Halme, Leena; Koskinen, Lotta L. E.; Ananthakrishnan, Ashwin N.; Luo, Yang; Heap, Graham A.; Visschedijk, Marijn C.; MacArthur, Daniel G.; Neale, Benjamin M.; Ahmad, Tariq; Anderson, Carl A.; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Palotie, Aarno; Saavalainen, Paivi; Kontula, Kimmo; Farkkila, Martti; McGovern, Dermot P. B.; Franke, Andre; Stefansson, Kari; Rioux, John D.; Xavier, Ramnik J.; Daly, Mark J.

    Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants

  1. Genetics Home Reference: Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant

    Science.gov (United States)

    ... SBBYS variant Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant Printable PDF Open All Close All Enable ... collapse boxes. Description The Say-Barber-Biesecker-Young-Simpson (SBBYS) variant of Ohdo syndrome is a rare ...

  2. Genotype–phenotype correlations in individuals with pathogenic RERE variants

    Science.gov (United States)

    Jordan, Valerie K.; Fregeau, Brieana; Ge, Xiaoyan; Giordano, Jessica; Wapner, Ronald J.; Balci, Tugce B.; Carter, Melissa T.; Bernat, John A.; Moccia, Amanda N.; Srivastava, Anshika; Martin, Donna M.; Bielas, Stephanie L.; Pappas, John; Svoboda, Melissa D.; Rio, Marlène; Boddaert, Nathalie; Cantagrel, Vincent; Lewis, Andrea M.; Scaglia, Fernando; Kohler, Jennefer N.; Bernstein, Jonathan A.; Dries, Annika M.; Rosenfeld, Jill A.; DeFilippo, Colette; Thorson, Willa; Yang, Yaping; Sherr, Elliott H.; Bi, Weimin; Scott, Daryl A.

    2018-01-01

    Heterozygous variants in the arginine-glutamic acid dipeptide repeats gene (RERE) have been shown to cause neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH). Here, we report nine individuals with NEDBEH who carry partial deletions or deleterious sequence variants in RERE. These variants were found to be de novo in all cases in which parental samples were available. An analysis of data from individuals with NEDBEH suggests that point mutations affecting the Atrophin-1 domain of RERE are associated with an increased risk of structural eye defects, congenital heart defects, renal anomalies, and sensorineural hearing loss when compared with loss-of-function variants that are likely to lead to haploinsufficiency. A high percentage of RERE pathogenic variants affect a histidine-rich region in the Atrophin-1 domain. We have also identified a recurrent two-amino-acid duplication in this region that is associated with the development of a CHARGE syndrome-like phenotype. We conclude that mutations affecting RERE result in a spectrum of clinical phenotypes. Genotype–phenotype correlations exist and can be used to guide medical decision making. Consideration should also be given to screening for RERE variants in individuals who fulfill diagnostic criteria for CHARGE syndrome but do not carry pathogenic variants in CHD7. PMID:29330883

  3. Gain-of-function HCN2 variants in genetic epilepsy.

    Science.gov (United States)

    Li, Melody; Maljevic, Snezana; Phillips, A Marie; Petrovski, Slave; Hildebrand, Michael S; Burgess, Rosemary; Mount, Therese; Zara, Federico; Striano, Pasquale; Schubert, Julian; Thiele, Holger; Nürnberg, Peter; Wong, Michael; Weisenberg, Judith L; Thio, Liu Lin; Lerche, Holger; Scheffer, Ingrid E; Berkovic, Samuel F; Petrou, Steven; Reid, Christopher A

    2018-02-01

    Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also independently identified in an unrelated patient with childhood absence seizures from a European cohort of 238 familial GGE cases. The p.V246M variant was identified in a patient with photo-sensitive GGE and his father diagnosed with juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and p.V246M had an identical functional impact including a depolarizing shift in the voltage dependence of activation that is consistent with a gain-of-function. In contrast, no biophysical changes resulted from the introduction of common population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that did not segregate with disease. Our data suggest that HCN2 variants can confer susceptibility to GGE via a gain-of-function mechanism. © 2017 Wiley Periodicals, Inc.

  4. NMNAT1 variants cause cone and cone-rod dystrophy.

    Science.gov (United States)

    Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

    2018-03-01

    Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

  5. A geometric framework for evaluating rare variant tests of association.

    Science.gov (United States)

    Liu, Keli; Fast, Shannon; Zawistowski, Matthew; Tintle, Nathan L

    2013-05-01

    The wave of next-generation sequencing data has arrived. However, many questions still remain about how to best analyze sequence data, particularly the contribution of rare genetic variants to human disease. Numerous statistical methods have been proposed to aggregate association signals across multiple rare variant sites in an effort to increase statistical power; however, the precise relation between the tests is often not well understood. We present a geometric representation for rare variant data in which rare allele counts in case and control samples are treated as vectors in Euclidean space. The geometric framework facilitates a rigorous classification of existing rare variant tests into two broad categories: tests for a difference in the lengths of the case and control vectors, and joint tests for a difference in either the lengths or angles of the two vectors. We demonstrate that genetic architecture of a trait, including the number and frequency of risk alleles, directly relates to the behavior of the length and joint tests. Hence, the geometric framework allows prediction of which tests will perform best under different disease models. Furthermore, the structure of the geometric framework immediately suggests additional classes and types of rare variant tests. We consider two general classes of tests which show robustness to noncausal and protective variants. The geometric framework introduces a novel and unique method to assess current rare variant methodology and provides guidelines for both applied and theoretical researchers. © 2013 Wiley Periodicals, Inc.

  6. Behavioural-variant frontotemporal dementia: An update

    Directory of Open Access Journals (Sweden)

    Olivier Piguet

    Full Text Available ABSTRACT Behavioural-variant frontotemporal dementia (bvFTD is characterised by insidious changes in personality and interpersonal conduct that reflect progressive disintegration of the neural circuits involved in social cognition, emotion regulation, motivation and decision making. The underlying pathology is heterogeneous and classified according to the presence of intraneuronal inclusions of tau, TDP-43 or occasionally FUS. Biomarkers to detect these histopathological changes in life are increasingly important with the development of disease-modifying drugs. Gene mutations have been found which collectively account for around 10-20% of cases including a novel hexanucleotide repeat on chromosome 9 (C9orf72. The recently reviewed International Consensus Criteria for bvFTD propose three levels of diagnostic certainly: possible, probable and definite. Detailed history taking from family members to elicit behavioural features underpins the diagnostic process with support from neuropsychological testing designed to detect impairment in decision-making, emotion processing and social cognition. Brain imaging is important for increasing the level of diagnosis certainty. Carer education and support remain of paramount importance.

  7. Spatially variant morphological restoration and skeleton representation.

    Science.gov (United States)

    Bouaynaya, Nidhal; Charif-Chefchaouni, Mohammed; Schonfeld, Dan

    2006-11-01

    The theory of spatially variant (SV) mathematical morphology is used to extend and analyze two important image processing applications: morphological image restoration and skeleton representation of binary images. For morphological image restoration, we propose the SV alternating sequential filters and SV median filters. We establish the relation of SV median filters to the basic SV morphological operators (i.e., SV erosions and SV dilations). For skeleton representation, we present a general framework for the SV morphological skeleton representation of binary images. We study the properties of the SV morphological skeleton representation and derive conditions for its invertibility. We also develop an algorithm for the implementation of the SV morphological skeleton representation of binary images. The latter algorithm is based on the optimal construction of the SV structuring element mapping designed to minimize the cardinality of the SV morphological skeleton representation. Experimental results show the dramatic improvement in the performance of the SV morphological restoration and SV morphological skeleton representation algorithms in comparison to their translation-invariant counterparts.

  8. CRY2 genetic variants associate with dysthymia.

    Directory of Open Access Journals (Sweden)

    Leena Kovanen

    Full Text Available People with mood disorders often have disruptions in their circadian rhythms. Recent molecular genetics has linked circadian clock genes to mood disorders. Our objective was to study two core circadian clock genes, CRY1 and CRY2 as well as TTC1 that interacts with CRY2, in relation to depressive and anxiety disorders. Of these three genes, 48 single-nucleotide polymorphisms (SNPs whose selection was based on the linkage disequilibrium and potential functionality were genotyped in 5910 individuals from a nationwide population-based sample. The diagnoses of major depressive disorder, dysthymia and anxiety disorders were assessed with a structured interview (M-CIDI. In addition, the participants filled in self-report questionnaires on depressive and anxiety symptoms. Logistic and linear regression models were used to analyze the associations of the SNPs with the phenotypes. Four CRY2 genetic variants (rs10838524, rs7121611, rs7945565, rs1401419 associated significantly with dysthymia (false discovery rate q<0.05. This finding together with earlier CRY2 associations with winter depression and with bipolar type 1 disorder supports the view that CRY2 gene has a role in mood disorders.

  9. Variant Carvajal syndrome with additional dental anomalies.

    Science.gov (United States)

    Barber, Sophy; Day, Peter; Judge, Mary; Toole, Edell O'; Fayle, Stephen

    2012-09-01

    This paper aims to review the case of a girl who presented with a number of dental anomalies, in addition to unusual skin, nail and hair conditions. Tragically an undiagnosed cardiomyopathy caused unexpected sudden death. The case is discussed with reference to a number of dermatological and oral conditions which were considered as possible diagnoses. AW had been under long term dental care for prepubertal periodontitis, premature root resorption of primary teeth, soft tissue and dental anomalies, and angular cheilitis. Separately she had also been seen by several dermatologists with respect to palmar plantar keratosis, striae keratoderma, wiry hair and abnormal finger nails. Tragically the patient suffered a sudden unexpected death and the subsequent post mortem identified an undiagnosed dilated cardiomyopathy. The most likely diagnosis is that this case is a variant of Carvajal Syndrome with additional dental anomalies. To date we have been unable to identify mutations in the desoplakin gene. We aim to emphasise the importance of recognising these dental and dermatological signs when they present together as a potential risk factor for cardiac abnormalities. © 2012 The Authors. International Journal of Paediatric Dentistry © 2012 BSPD, IAPD and Blackwell Publishing Ltd.

  10. Identification of copy number variants in horses

    KAUST Repository

    Doan, R.

    2012-03-01

    Copy number variants (CNVs) represent a substantial source of genetic variation in mammals. However, the occurrence of CNVs in horses and their subsequent impact on phenotypic variation is unknown. We performed a study to identify CNVs in 16 horses representing 15 distinct breeds (Equus caballus) and an individual gray donkey (Equus asinus) using a whole-exome tiling array and the array comparative genomic hybridization methodology. We identified 2368 CNVs ranging in size from 197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and 99.4 kb, respectively. Approximately 6% of the genes investigated were affected by a CNV. Biological process enrichment analysis indicated CNVs primarily affected genes involved in sensory perception, signal transduction, and metabolism. CNVs also were identified in genes regulating blood group antigens, coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and height in other species. Collectively, these data are the first report of copy number variation in horses and suggest that CNVs are common in the horse genome and may modulate biological processes underlying different traits observed among horses and horse breeds.

  11. Human papillomavirus type-16 variants in Quechua aboriginals from Argentina.

    Science.gov (United States)

    Picconi, María Alejandra; Alonio, Lidia Virginia; Sichero, Laura; Mbayed, Viviana; Villa, Luisa Lina; Gronda, Jorge; Campos, Rodolfo; Teyssié, Angélica

    2003-04-01

    Cervical carcinoma is the leading cause of cancer death in Quechua indians from Jujuy (northwestern Argentina). To determine the prevalence of HPV-16 variants, 106 HPV-16 positive cervical samples were studied, including 33 low-grade squamous intraepithelial lesions (LSIL), 28 high-grade squamous intraepithelial lesions (HSIL), 9 invasive cervical cancer (ICC), and 36 samples from women with normal colposcopy and cytology. HPV genome variability was examined in the L1 and E6 genes by PCR-hybridization. In a subset of 20 samples, a LCR fragment was also analyzed by PCR-sequencing. Most variants belonged to the European branch with subtle differences that depended on the viral gene fragment studied. Only about 10% of the specimens had non-European variants, including eight Asian-American, two Asian, and one North-American-1. E6 gene analysis revealed that 43% of the samples were identical to HPV-16 prototype, while 57% corresponded to variants. Interestingly, the majority (87%) of normal smears had HPV-16 prototype, whereas variants were detected mainly in SIL and ICC. LCR sequencing yielded 80% of variants, including 69% of European, 19% Asian-American, and 12% Asian. We identified a new variant, the Argentine Quechua-51 (AQ-51), similar to B-14 plus two additional changes: G7842-->A and A7837-->C; phylogenetic inference allocated it in the Asian-American branch. The high proportion of European variants may reflect Spanish colonial influence on these native Inca descendants. The predominance of HPV-16 variants in pathologic samples when compared to normal controls could have implications for the natural history of cervical lesions. Copyright 2003 Wiley-Liss, Inc.

  12. A variational Bayes discrete mixture test for rare variant association.

    Science.gov (United States)

    Logsdon, Benjamin A; Dai, James Y; Auer, Paul L; Johnsen, Jill M; Ganesh, Santhi K; Smith, Nicholas L; Wilson, James G; Tracy, Russell P; Lange, Leslie A; Jiao, Shuo; Rich, Stephen S; Lettre, Guillaume; Carlson, Christopher S; Jackson, Rebecca D; O'Donnell, Christopher J; Wurfel, Mark M; Nickerson, Deborah A; Tang, Hua; Reiner, Alexander P; Kooperberg, Charles

    2014-01-01

    Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that "aggregate" tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare-variant test that explicitly models a fraction of variants as neutral, tests associations at the gene-level, and infers the rare-variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome-wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare-variants imputed from the National Heart, Lung, and Blood Institute's Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (~10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans.

  13. Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

    Science.gov (United States)

    Doluoglu, Omer Gokhan; Ceylan, Cavit; Kilinc, Fatih; Gazel, Eymen; Resorlu, Berkan; Odabas, Oner

    2016-01-01

    We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer. The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5-20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6-20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32). Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa.

  14. Patient Perceptions of Breast Cancer Risk in Imaging-Detected Low-Risk Scenarios and Thresholds for Desired Intervention: A Multi-Institution Survey.

    Science.gov (United States)

    Grimm, Lars J; Shelby, Rebecca A; Knippa, Emily E; Langman, Eun L; Miller, Lauren S; Whiteside, Beth E; Soo, Mary Scott C

    2018-06-01

    To determine women's perceptions of breast cancer risk and thresholds for desiring biopsy when considering BI-RADS 3 and 4A scenarios and recommendations, respectively. Women presenting for screening mammography from five geographically diverse medical centers were surveyed. Demographic information and baseline anxiety were queried. Participants were presented with scenarios of short-term imaging follow-up recommendations (ie, BI-RADS 3) and biopsy recommendations (ie, BI-RADS 4A) for low-risk mammographic abnormalities and asked to estimate their breast cancer risk for each scenario. Participants reported the threshold (ie, likelihood of cancer) where they would feel comfortable undergoing short-term imaging follow-up and biopsy and their anticipated regret for choosing short-term follow-up versus biopsy. Analysis of 2,747 surveys showed that participants estimated breast cancer risk of 32.8% for a BI-RADS 3 and 41.1% for a BI-RADS 4A scenarios are significantly greater rates than clinically established rates (<2% [P < .001] and 2%-10% [P < .001], respectively). Over one-half (55.4%) of participants reported they would never want imaging follow-up if there was any chance of cancer; two-thirds (66.2%) reported they would desire biopsy if there was any chance of cancer. Participants reported greater anticipated regret (P < .001) and less relief and confidence (P < .001) with the decision to undergo follow-up imaging versus biopsy. Women overestimate breast cancer risk associated with both BI-RADS 3 and 4A scenarios and desire very low biopsy thresholds. Greater anticipated regret and less relief and confidence was reported with the choice to undergo short-term imaging follow-up compared with biopsy. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  15. [Comparison of 64 MDCT coronary CTA and coronary angiography in the detection of coronary artery stenosis in low risk patients with stable angina and acute coronary syndrome].

    Science.gov (United States)

    Cazalas, G; Sarran, A; Amabile, N; Chaumoitre, K; Marciano-Chagnaud, S; Jacquier, A; Paganelli, F; Panuel, M

    2009-09-01

    To determine the accuracy of 64 MDCT coronary CTA (CCTA) compared to coronary angiography in low risk patients with stable angina and acute coronary syndrome and determine the number of significant coronary artery stenoses ( 50%) in these patients. Materials and methods. Fifty-five patients underwent CCTA using a 32 MDCT unit with z flying focus allowing the acquisition of 64 slices of 0.6 mm thickness as well as coronary angiography (gold standard). Nine patients were excluded due to prior coronary artery bypass surgery (n=4), insufficient breath hold (n=3), calcium scoring>1000 (n=1) and delay between both examinations over 4 months (n=1). Forty-six patients: 27 males and 19 females were included. CCTA results were compared to coronary angiography per segment and artery with threshold detection of stenoses 50%. The degree of correlation between both examinations was performed using a regression analysis with a Pearson correlation coefficient<0.05 considered significant. The overall accuracy of CCTA was 90%; limitations related to the presence of calcifications, motion artifacts or insufficient vessel opacification. The correlation for all analyzed segments was 96.4%. Thirty-eight of 50 significant stenoses seen on coronary angiography were correctly detected on CCTA. Sensitivity, specificity, PPVC and NPV for detection of stenoses 50% were 76%, 98.3%, 80.3% and 97.7% respectively. Evaluation per segment had a NPV of 96.8% (interventricular and diagonal segments) to 100% (main trunk). Our results for specificity and NPV are similar to reports from the literature. This suggests that CCTA in this clinical setting may replace coronary angiography.

  16. Risk of spontaneous preterm delivery in a low-risk population: the impact of maternal febrile episodes, urinary tract infection, pneumonia and ear-nose-throat infections.

    Science.gov (United States)

    Morken, Nils-Halvdan; Gunnes, Nina; Magnus, Per; Jacobsson, Bo

    2011-12-01

    To assess the associations between maternal infections during pregnancy (i.e. ear-nose-throat infection, pneumonia, urinary tract infection, febrile episodes and influenza-like infection) and spontaneous preterm delivery (SPTD). Prospective questionnaire data from the Norwegian Mother and Child Cohort (MoBa) study, including more than 100000 pregnancies and, collected during 1999-2008, were used. Linked data from the Medical Birth Registry of Norway were added. SPTD occurring between gestational weeks 22+0 days and 36+6 days was the main outcome. Data were analysed in two steps because questionnaires (including information about occurrence of the various infections so far) were completed at different stages of pregnancy. Hazard ratios (HR) were obtained using Cox regression. The SPTD proportion was low in this cohort: 2.9% and 2.7% at the two analysis steps, respectively. After exclusions, 67310 and 60689 pregnancies, respectively, remained for the analyses. Ear-nose-throat infections occurring before week 17 were associated with an increased risk of SPTD in the first (HR: 1.27, 95% CI: 1.08-1.50) and second (HR: 1.26, 95% CI: 1.04-1.52) step of the analysis, but not if occurring later in pregnancy. None of the other maternal infections were associated with an increased risk of SPTD. In this low-risk population, ear-nose-throat infection in early pregnancy was associated with an increased risk of SPTD. However, infectious morbidity in later pregnancy was not. Thus, the link between maternal infection and preterm delivery may vary in different populations and health care settings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Contrast-enhanced spectral mammography as work-up tool in patients recalled from breast cancer screening has low risks and might hold clinical benefits.

    Science.gov (United States)

    Houben, I P L; Van de Voorde, P; Jeukens, C R L P N; Wildberger, J E; Kooreman, L F; Smidt, M L; Lobbes, M B I

    2017-09-01

    Contrast-enhanced spectral mammography (CESM) is a reliable problem solving tool in the work-up of women recalled from breast cancer screening. We evaluated additional findings caused by CESM alone and outweighed them against the disadvantages of this technique. From December 2012 to December 2015, all women recalled from screening who underwent CESM were considered for this study. Radiation exposure and number of adverse contrast reactions were analysed. An experienced breast radiologist reviewed all exams and identified cases with lesions detected by CESM alone and scored their conspicuity. From these cases, data on breast density and final diagnosis were collected. For malignant cases, tumour grade and receptor characteristics were also collected. During this study, 839 women underwent CESM after a screening recall, in which five minor adverse contrast reactions were observed. Median radiation dose per exam was 6.0mGy (0.9-23.4mGy). Seventy CESM-only lesions were detected in 65 patients. Of these 70 lesions, 54.3% proved to be malignant, most commonly invasive ductal carcinomas. The remaining CESM-only lesions were benign, predominantly fibroadenomas. No complications were observed during biopsy of these lesions. Retrospectively, the majority of the lesions were either occult or a 'minimal sign' on low-energy CESM images or the screening mammogram. Using CESM as a work-up tool for women recalled from screening carries low risk for the patient, while additionally detected tumour foci might hold important clinical implications which need to be further studied in large, randomized controlled trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Application of National Emergency X-Ray Utilizations Study low-risk c-spine criteria in high-risk geriatric falls.

    Science.gov (United States)

    Evans, Daniel; Vera, Luis; Jeanmonod, Donald; Pester, Jonathan; Jeanmonod, Rebecca

    2015-09-01

    We sought to validate National Emergency X-Radiography Utilizations Study low-risk cervical spine (C spine) criteria in a geriatric trauma population. We sought to determine whether patients' own baseline mental status (MS) could substitute for Glasgow Coma Scale (GCS) to meet the criteria "normal alertness." We further sought to refine the definition of "distracting injury." This is a retrospective review of geriatric fall patients presenting to a level 1 trauma center and triaged to the trauma bay. We queried our database from 2008 to 2013. Abstractors recorded GCS, deviation from baseline MS, midline neck tenderness, intoxication, focal deficit, signs of trauma, and presence of other injury. Patients were considered at baseline MS if specific documentation was present on the chart, or if their GCS was 15. Six hundred sixty elderly fall patients were trauma alerts during the study period. Seventeen were excluded for incomplete records/death before imaging, leaving 647. The median age was 81 (interquartile range, 74-87). Fifty patients (8.0%) had C spine or cord injury. Two hundred ninety-four (44.5%) had baseline MS (including GCS 13-15), no spine tenderness, no intoxication, and no focal neurologic deficit. Of these, 18 had C-spine injury. Using physical findings of head trauma as the only "distracting injury," no injury would have been missed (sensitivity, 100% [confidence interval, 91.1-100]; specificity, 14.2%). Our study suggests that National Emergency X-Radiography Utilizations Study can be safely applied in elderly fall patients who are at their personal baseline MS. Furthermore, our data support a more narrow definition of distracting injury to include only patients with signs of trauma to the head. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. The comparison of birth outcomes and birth experiences of low-risk women in different sized midwifery practices in the Netherlands.

    Science.gov (United States)

    Fontein, Yvonne

    2010-09-01

    To examine maternal birth outcomes and birth experiences of low-risk women in the Netherlands in different sized midwifery practices. Descriptive study using postal questionnaires six weeks after the estimated due date. Women were recruited from urban, semi-rural and rural areas from small-sized practices (1-2 midwives), medium-sized practices (3-4 midwives) or large-sized practices (5 or more). 718 Dutch speaking women with uncomplicated pregnancies, a representative sample of women in 143 midwifery practices in the Netherlands who had given birth in the period between 20 April and 20 May 2007. Distribution of place of birth categories and intervention categories, birth experience, woman-midwife relationship and presence of own midwife after referral. Data were analyzed with Statistical Package for Social Sciences (SPSS). Women in practices with a maximum of two midwives were significantly more likely to experience lower rates of referral, interventions in general and specifically pain relief by means of pethidine, CTG registration and unplanned caesarean sections. Women with a maximum of two midwives were significantly more likely to know their midwife or midwives and were more frequently supported by their own midwife after referral in comparison to women in practices with more than two midwives. The presence of the woman's own midwife added value to the birth experience. Women with a maximum of two midwives had higher levels of a positive birth experience than women in practices with more than two midwives. Midwifery practices with a maximum of two midwives contribute to non-interventionist birth and a positive birth experience. Awareness of the study results and further study is recommended to discuss reorganization of care in order to achieve significant reductions on referral and interventions during childbirth and positive maternal birth experiences. Copyright (c) 2010 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  20. Outcomes of planned home births and planned hospital births in low-risk women in Norway between 1990 and 2007: a retrospective cohort study.

    Science.gov (United States)

    Blix, Ellen; Huitfeldt, Anette Schaumburg; Øian, Pål; Straume, Bjørn; Kumle, Merethe

    2012-12-01

    The safety of planned home births remains controversial in Western countries. The aim of the present study was to compare outcomes in women who planned, and were selected to, home birth at the onset of labor with women who planned for a hospital birth. Data from 1631 planned home births between 1990 and 2007 were compared with a random sample of 16,310 low-risk women with planned hospital births. The primary outcomes were intrapartum intervention rates and complications. Secondary outcomes were perinatal and neonatal death rates. Primiparas who planned home births had reduced risks for assisted vaginal delivery (OR 0.32; 95% CI 0.20-0.48), epidural analgesia (OR 0.21; CI 0.14-0.33) and dystocia (OR 0.40; CI 0.27-0.59). Multiparas who planned home births had reduced risks for operative vaginal delivery (OR 0.26; CI 0.12-0.56), epidural analgesia (OR 0.08; CI 0.04-0.16), episiotomy (OR 0.48; CI 0.31-0.75), anal sphincter tears (OR 0.29; CI 0.12-0.70), dystocia (OR 0.10; CI 0.06-0.17) and postpartum hemorrhage (OR 0.27; CI 0.17-0.41). We found no differences in cesarean section rate. Perinatal mortality rate was 0.6/1000 (CI 0-3.4) and neonatal mortality rate 0.6/1000 (CI 0-3.4) in the home birth cohort. In the hospital birth cohort, the rates were 0.6/1000 (CI 0.3-1.1) and 0.9/1000 (CI 0.5-1.5) respectively. Planning for home births was associated with reduced risk of interventions and complications. The study is too small to make statistical comparisons of perinatal and neonatal mortality. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Effects of maternal absence due to employment on the quality of infant-mother attachment in a low-risk sample.

    Science.gov (United States)

    Barglow, P; Vaughn, B E; Molitor, N

    1987-08-01

    Recent reports have suggested that day-care experience initiated prior to 12 months of age is associated with increased proportions of infants whose attachment to mother is classified as "insecure-avoidant." However, reviewers have questioned the generality of these findings, noting that samples in which associations between early day-care experience and avoidant attachment patterns have been reported come from high-risk populations, and/or that the infants' day-care settings may not have been of high quality. In the present study, effects of maternal absences on infant-mother attachment quality were assessed in a low-risk, middle-class sample (N = 110). In all instances, substitute care had been initiated at least 4 months prior to the infant's first birthday and was provided in the infant's home by a person unrelated to the baby. Infants were assessed using the Ainsworth Strange Situation when they were 12-13 months of age. Analyses indicated that a significantly greater proportion of infants whose mothers worked outside the home (N = 54) were assigned to the category "insecure-avoidant" as compared to infants whose mothers remained in the home (N = 56) throughout the first year of life. Analyses of demographic and psychological data available for the sample indicated that this relation is dependent upon maternal parity (primi- vs. multiparous mother). The association between attachment quality and work status was significant only for firstborn children of full-time working mothers. The results are interpreted as evidence that the repeated daily separations experienced by infants whose mothers are working full-time constitute a "risk" factor for the development of "insecure-avoidant" infant-mother attachments.

  2. Outcomes of Incidental Fallopian Tube High-Grade Serous Carcinoma and Serous Tubal Intraepithelial Carcinoma in Women at Low Risk of Hereditary Breast and Ovarian Cancer.

    Science.gov (United States)

    Chay, Wen Yee; McCluggage, W Glenn; Lee, Cheng-Han; Köbel, Martin; Irving, Julie; Millar, Joanne; Gilks, C Blake; Tinker, Anna V

    2016-03-01

    The natural history and optimal management of serous tubal intraepithelial carcinoma (STIC), regardless of BRCA status, is unknown. We report the follow-up findings of a series of incidental fallopian tube high-grade serous carcinomas (HGSCs) and STICs identified in women at low risk for hereditary breast and ovarian cancer (HBOC), undergoing surgery for other indications. Cases of incidental STIC and HGSC were identified from 2008. Patients with known BRCA1 or BRCA2 mutations, or a family history of ovarian or breast cancer before the diagnosis of STIC or HGSC were excluded. A retrospective chart review was conducted to obtain clinical data. Eighteen cases were identified with a median follow-up of 25 months (range, 4-88 months). Twelve of 18 patients had a diagnosis of STIC with no associated invasive HGSC and 6 had STIC associated with other invasive malignancies. Completion staging surgery was performed on 7 of the 18 patients, including 5 of 12 in which there was STIC only identified on primary surgery; 3 cases were upstaged from STIC only to HGSC based on the staging surgery. Recurrence of HGSC occurred in 2 of the 18 patients. BRCA testing was performed on 3 patients, 1 of whom tested positive for a pathogenic BRCA1 mutation. Our study suggests that completion staging surgery for incidental STICs in non-BRCA patients may be considered. These patients should be offered hereditary testing. The Pelvic-Ovarian cancer INTerception (POINT) Project is an international registry set up to add to our understanding of STICs.

  3. Alcohol consumption and low-risk drinking guidelines among adults: a cross-sectional analysis from Alberta’s Tomorrow Project

    Science.gov (United States)

    Darren R., Brenner; Tiffany R., Haig; Abbey E, Poirier; Alianu, Akawung; Christine M., Friedenreich; Paula J., Robson

    2017-01-01

    strategies to promote low-risk drinking among those who choose to drink could impact future chronic disease risk in this population. PMID:29236379

  4. High-risk and low-risk human papilloma virus in association to spontaneous preterm labor: a case-control study in a tertiary center, Egypt.

    Science.gov (United States)

    Mosbah, Alaa; Barakat, Rafik; Nabiel, Yasmin; Barakat, Ghada

    2018-03-01

    This study aimed to detect the correlation between human papillomavirus (HPV) and spontaneous preterm labor in Egyptian women and its association to the human papilloma viral load and MPP2 gene expression. We performed an observational comparative case-control study in Department of Obstetric and Gynecology, Mansoura University Hospitals over women presented with spontaneous preterm labor, besides females admitted for giving birth at full term to detect conserved sequence in HPV-L1 gene (GP5/GP6) followed by genotype detection of high- and low-risk HPVs with quantification of the viral load and the MMP2 gene expression using real-time polymerase chain reaction (PCR). The prevalence of HPV was 18.1% in preterm females, but only 4% in full-term women (p value = 0.019*). Twenty percent were PCR positive for HPV 16 and 40% for HPV 18 whereas none of the control was positive for any of the studied high-risk genotypes. Thirty percent were PCR positive for HPV 6 and 10% were positive for HPV 11. MMP2 gene expression was significantly higher in preterm than full term. Human papilloma viral load was found to be positively correlated to the rate of MMP2 expression and the gestational age was significantly related to the viral load and the rate of expression of MMP2 gene. Human pabilloma virus especially high-risk genotypes was correlated to spontaneous preterm labor in Egyptian females through increasing early expression of MMP2 gene. The time of occurrence of preterm labor was affected by the viral load and so the rate of expression of MMP2 gene.

  5. Age-related changes of healthy bone marrow cell signaling in response to growth factors provide insight into low risk MDS.

    Science.gov (United States)

    Kornblau, Steven M; Cohen, Aileen C; Soper, David; Huang, Ying-Wen; Cesano, Alessandra

    2014-11-01

    Single Cell Network Profiling (SCNP) is a multiparametric flow cytometry-based assay that quantifiably and simultaneously measures changes in intracellular signaling proteins in response to in vitro extracellular modulators at the single cell level. Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder of hematopoietic stem cells that occurs in elderly subjects and is characterized by dysplasia and ineffective hematopoiesis. The functional responsiveness of MDS bone marrow (BM) hematopoietic cells, including functionally distinct myeloid and erythroid precursor subsets, to hematopoietic growth factors (HGF) and the relationship of modulated signaling to disease characteristics is poorly understood. SCNP was used first to examine the effects of age on erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF)-induced signaling in myeloid, nucleated red blood cells (nRBC), and CD34 expressing cell subsets in healthy BM (n = 15). SCNP was then used to map functional signaling profiles in low risk (LR) MDS (n = 7) for comparison to signaling in samples from healthy donors and to probe signaling associations within clinically defined subgroups. In healthy BM samples, signaling responses to HGF were quite homogeneous (i.e., tightly regulated) with age-dependent effects observed in response to EPO but not to GCSF. Despite the relatively small number of samples assayed in the study, LR MDS could be classified into distinct subgroups based on both cell subset frequency and signaling profiles. As a correlate of underlying genetic abnormalities, signal transduction analyses may provide a functional and potentially clinically relevant classification of MDS. Further evaluation in a larger cohort is warranted. © 2013 Clinical Cytometry Society.

  6. Structure of chymotrypsin variant B from Atlantic cod, Gadus morhua

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Asgeirsson, B; Thórólfsson, M

    1996-01-01

    The amino-acid sequence of chymotrypsin variant B isolated from the pyloric caeca of Atlantic cod has been elucidated. The characterization of the primary structure is based on N-terminal Edman degradation and mass spectrometry of the native protein and enzymatically derived peptides. Chymotrypsi...... autolysis sites, cod variant B only contains a single autolysis site. The three-dimensional structures of the A- and B-variants of cod has been modelled on the known crystal structure of bovine alpha-chymotrypsin showing almost superimposable structures....

  7. Variant of Rett syndrome and CDKL5 gene

    DEFF Research Database (Denmark)

    Pini, Giorgio; Bigoni, Stefania; Engerström, Ingegerd Witt

    2012-01-01

    UNLABELLED: Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. AIMS: In recent years more than 60 patients with mutations in the CDKL5 gene have...... been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. METHODS: 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all...

  8. Radioimmunological activity of 22K variant of human growth hormone

    International Nuclear Information System (INIS)

    Camillo, M.A.P.; Ribela, M.T.C.P.; Rogero, J.R.

    1986-01-01

    From a preparation of human growth hormone its integral variant (hGH-22K) was isolated by isoelectric focusing, having a pI of 5,20 and relative mobility (Rm) of 0,621 in the polyacrylamide gel electrophoresis. Several experiments for the characterization of the isolated variant were carried out. The immunological properties was tested by radioimmunoassay (RIE), in which the activity of the isolated variant and the activity of the total preparation were compared. The dose response-curves obtained by RIE were found to be considered parallels (p [pt

  9. Perinatal mortality and morbidity up to 28 days after birth among 743 070 low-risk planned home and hospital births: a cohort study based on three merged national perinatal databases

    NARCIS (Netherlands)

    de Jonge, A.; Geerts, C.C.; van der Goes, B.Y.; Mol, B.W.; Buitendijk, S.E.; Nijhuis, J.G.

    2015-01-01

    Objective To compare rates of adverse perinatal outcomes between planned home births versus planned hospital births. Design A nationwide cohort study. Setting The Netherlands. Population Low-risk women in midwife-led care at the onset of labour. Methods Analysis of national registration data. Main

  10. Perinatal mortality and morbidity up to 28 days after birth among 743 070 low-risk planned home and hospital births: a cohort study based on three merged national perinatal databases

    NARCIS (Netherlands)

    de jonge, A.; Geerts, C. C.; van der Goes, B. Y.; Mol, B. W.; Buitendijk, S. E.; Nijhuis, J. G.

    2015-01-01

    To compare rates of adverse perinatal outcomes between planned home births versus planned hospital births. A nationwide cohort study. The Netherlands. Low-risk women in midwife-led care at the onset of labour. Analysis of national registration data. Intrapartum and neonatal death, Apgar scores, and

  11. Variante de Dandy Walker: relato de caso = Dandy Walker variant: a case report

    Directory of Open Access Journals (Sweden)

    Khan, Richard Lester

    2009-01-01

    Conclusões: este artigo procura caracterizar a variante de Dandy Walker, que é uma malformação congênita do sistema nervoso central e é o tipo mais comum da Síndrome de Dandy Walker. Seu fenótipo é variável, devendo-se sempre pesquisar malformações tanto intra quanto extracranianas, visto que o risco de mortalidade pós-natal aumenta quando existe esta associação. O tratamento envolve equipe multidisciplinar e o prognóstico é reservado, variando conforme o fenótipo

  12. Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia.

    Science.gov (United States)

    Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A; Cogan, Joy; Blackwell, Timothy S; Phillips, John A; Bush, William S; Meiler, Jens; Capra, John A

    2018-01-23

    Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease. To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function. Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating

  13. Financial impact of outpatient clinic radioiodine therapy with sodium iodide I-131 for the treatment of patients with differentiated low-risk thyroid carcinoma in relation to hospital doses

    International Nuclear Information System (INIS)

    Berenguer, P.F.; Chang, T.M.C.; Silva, R.A.M.; Neto, A.H.D.; Belo, I.B.; Santos, M.A.P.

    2017-01-01

    Differential thyroid carcinoma (CDT) is the most prevalent endocrine malignancy in the world, with an excellent prognosis and a 10-year survival rate of over 95%. By 2013, the lowest activity of I-131 authorized by the Brazilian Unified Health System (SUS) in the therapy of patients with low-risk CDT was 3,700 MBq, requiring hospitalization. Recent studies have shown similar effectiveness between low and high doses of I-131 in the treatment of low-risk CDT. In 2014, the Ministry of Health included in the list of SUS procedures the use of lower activities (1,110 MBq and 1,850 MBq) for this purpose. The Brazilian National Nuclear Energy Commission (CNEN) also authorized the outpatient use of activity up to 1,850 MBq of I-131. Objective: To evaluate the financial impact of the adoption of ambulatory radioiodine therapy in patients with CDT of low-risk when compared to the hospital dose. Methods: Analysis of patients with CDT low-risk who were treated with an outpatient dose of I-131 from August / 2014 to January / 2017 at a nuclear medicine service in Recife, PE, Brazil. The cost of outpatient versus hospital doses was calculated. Results: A total of 289 patients underwent low doses of iodine therapy were evaluated, resulting in a savings of R$227,793.80. Conclusion: Outpatient radioiodine therapy in the treatment of patients with CDT of low-risk resulted in a 61.10% reduction in SUS expense, in addition to enabling faster care

  14. Myostatin: genetic variants, therapy and gene doping

    Directory of Open Access Journals (Sweden)

    André Katayama Yamada

    2012-09-01

    Full Text Available Since its discovery, myostatin (MSTN has been at the forefront of muscle therapy research because intrinsic mutations or inhibition of this protein, by either pharmacological or genetic means, result in muscle hypertrophy and hyperplasia. In addition to muscle growth, MSTN inhibition potentially disturbs connective tissue, leads to strength modulation, facilitates myoblast transplantation, promotes tissue regeneration, induces adipose tissue thermogenesis and increases muscle oxidative phenotype. It is also known that current advances in gene therapy have an impact on sports because of the illicit use of such methods. However, the adverse effects of these methods, their impact on athletic performance in humans and the means of detecting gene doping are as yet unknown. The aim of the present review is to discuss biosynthesis, genetic variants, pharmacological/genetic manipulation, doping and athletic performance in relation to the MSTN pathway. As will be concluded from the manuscript, MSTN emerges as a promising molecule for combating muscle wasting diseases and for triggering wide-ranging discussion in view of its possible use in gene doping.Desde sua descoberta, a miostatina (MSTN entrou na linha de frente em pesquisas relacionadas às terapias musculares porque mutações intrínsecas ou inibição desta proteína tanto por abordagens farmacológicas como genéticas resultam em hipertrofia muscular e hiperplasia. Além do aumento da massa muscular, a inibição de MSTN potencialmente prejudica o tecido conectivo, modula a força muscular, facilita o transplante de mioblastos, promove regeneração tecidual, induz termogênese no tecido adiposo e aumenta a oxidação na musculatura esquelética. É também sabido que os atuais avanços em terapia gênica têm uma relação com o esporte devido ao uso ilícito de tal método. Os efeitos adversos de tal abordagem, seus efeitos no desempenho de atletas e métodos para detectar doping genético s

  15. Adult schizophrenic-like variant of adrenoleukodystrophy.

    Science.gov (United States)

    Szpak, G M; Lewandowska, E; Schmidt-Sidor, B; Popow, J; Kozłowski, P; Lechowicz, W; Kulczycki, J; Zaremba, J; Dymecki, J

    1996-01-01

    A 35-year-old man died after 30 months following the onset of the disease. There was a history of changes in his mental condition, including disturbances of behavior as well as the evidence of progressing dementia. The patient revealed gait disturbances and finally became bed ridden. Bizarre behavior and changes of mood with concurrent growing irritability which predominated during the course of disease, may explain the initial diagnosis of schizophrenia. Then cerebellar and spastic movement disorders leading to paraparesis and sphincters disturbances developed. Clinical symptoms of adrenal failure were not found apart from episodes of arterial pressure fall. After two years a magnetic resonance imaging (MRI) revealed an extensive diffuse demyelinative process in white matter of cerebral and cerebellar hemispheres. Activity of lysosomal enzymes was normal. A general autopsy revealed atrophy of adrenal cortex and the presence of ballooned cells with striated cytoplasm in the reticular and fasciculate zones. Neuropathological examination revealed an extensive demyelination of white matter in cerebral and cerebellar hemispheres and of the long paths of the brain stem, corresponding to changes in MRI examination. Within demyelination areas damage of axons and diffuse cellular and fibrous gliosis were found as well as perivascular lymphocytic infiltrations with the presence of strong PAS (+) and Sudan (+) macrophages. Immunocytochemical reactions with HAM-56 and RCA1 in macrophages were positive. Electron microscopy examination revealed lamellar inclusions in cytoplasm of macrophages. Similar structures were present in the lysosomes of astrocytes. Morphological examination of adrenal glands as well as morphological and ultrastructural study of the brain allowed us to diagnose the cerebral form of adrenoleukodystrophy (ALD). Topography and character of the brain changes seems to be in keeping with a rare schizophrenic-like variant of ALD with progressive dementia

  16. Leapfrog variants of iterative methods for linear algebra equations

    Science.gov (United States)

    Saylor, Paul E.

    1988-01-01

    Two iterative methods are considered, Richardson's method and a general second order method. For both methods, a variant of the method is derived for which only even numbered iterates are computed. The variant is called a leapfrog method. Comparisons between the conventional form of the methods and the leapfrog form are made under the assumption that the number of unknowns is large. In the case of Richardson's method, it is possible to express the final iterate in terms of only the initial approximation, a variant of the iteration called the grand-leap method. In the case of the grand-leap variant, a set of parameters is required. An algorithm is presented to compute these parameters that is related to algorithms to compute the weights and abscissas for Gaussian quadrature. General algorithms to implement the leapfrog and grand-leap methods are presented. Algorithms for the important special case of the Chebyshev method are also given.

  17. Behavioral variant of frontotemporal dementia mimicking Huntington's disease

    DEFF Research Database (Denmark)

    Nielsen, T Rune; Bruhn, Peter; Nielsen, Jørgen E

    2010-01-01

    Behavioral changes and cognitive decline are the core clinical manifestations in the behavioral variant of frontotemporal dementia (bv-FTD). The behavioral changes may include characteristic stereotypic movements. These movements, although without clear purpose, are not involuntary. Involuntary...

  18. Variant Plasmodium ovale isolated from a patient infected in Ghana

    Directory of Open Access Journals (Sweden)

    Petersen Eskild

    2011-01-01

    Full Text Available Abstract Recent data have found that Plasmodium ovale can be separated in two distinct species: classic and variant P. ovale based on multilocus typing of different genes. This study presents a P. ovale isolate from a patient infected in Ghana together with an analysis of the small subunit RNA, cytochrome b, cytochrome c oxidase I, cysteine protease and lactate dehydrogenase genes, which show that the sample is a variant P. ovale and identical or highly similar to variant P. ovale isolated from humans in South-East Asia and Africa, and from a chimpanzee in Cameroon. The split between the variant and classic P. ovale is estimated to have occurred 1.7 million years ago.

  19. Genetic variant as a marker for bladder cancer therapy

    Science.gov (United States)

    Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

  20. Efficient population-scale variant analysis and prioritization with VAPr.

    Science.gov (United States)

    Birmingham, Amanda; Mark, Adam M; Mazzaferro, Carlo; Xu, Guorong; Fisch, Kathleen M

    2018-04-06

    With the growing availability of population-scale whole-exome and whole-genome sequencing, demand for reproducible, scalable variant analysis has spread within genomic research communities. To address this need, we introduce the Python package VAPr (Variant Analysis and Prioritization). VAPr leverages existing annotation tools ANNOVAR and MyVariant.info with MongoDB-based flexible storage and filtering functionality. It offers biologists and bioinformatics generalists easy-to-use and scalable analysis and prioritization of genomic variants from large cohort studies. VAPr is developed in Python and is available for free use and extension under the MIT License. An install package is available on PyPi at https://pypi.python.org/pypi/VAPr, while source code and extensive documentation are on GitHub at https://github.com/ucsd-ccbb/VAPr. kfisch@ucsd.edu.

  1. Genetic variants influencing lipid levels and risk of dyslipidemia in ...

    Indian Academy of Sciences (India)

    HUAICHAO LUO

    2017-12-18

    Dec 18, 2017 ... total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides. (TG) in 1900 ... in Chinese population, especially relationship between these genetic variants ...

  2. Common Gene Variants Account for Most Genetic Risk for Autism

    Science.gov (United States)

    ... gene variants account for most genetic risk for autism Roles of heritability, mutations, environment estimated – NIH-funded study. The bulk of risk, or liability, for autism spectrum disorders (ASD) was traced to inherited variations ...

  3. Method of generating ploynucleotides encoding enhanced folding variants

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.; Kiss, Csaba; Waldo, Geoffrey S.

    2017-05-02

    The invention provides directed evolution methods for improving the folding, solubility and stability (including thermostability) characteristics of polypeptides. In one aspect, the invention provides a method for generating folding and stability-enhanced variants of proteins, including but not limited to fluorescent proteins, chromophoric proteins and enzymes. In another aspect, the invention provides methods for generating thermostable variants of a target protein or polypeptide via an internal destabilization baiting strategy. Internally destabilization a protein of interest is achieved by inserting a heterologous, folding-destabilizing sequence (folding interference domain) within DNA encoding the protein of interest, evolving the protein sequences adjacent to the heterologous insertion to overcome the destabilization (using any number of mutagenesis methods), thereby creating a library of variants. The variants in the library are expressed, and those with enhanced folding characteristics selected.

  4. Genotype and phenotype spectrum of NRAS germline variants

    NARCIS (Netherlands)

    Altmuller, F.; Lissewski, C.; Bertola, D.; Flex, E.; Stark, Z.; Spranger, S.; Baynam, G.; Buscarilli, M.; Dyack, S.; Gillis, J.; Yntema, H.G.; Pantaleoni, F.; Loon, R.L. van; MacKay, S.; Mina, K.; Schanze, I.; Tan, T.Y.; Walsh, M.; White, S.M.; Niewisch, M.R.; Garcia-Minaur, S.; Plaza, D.; Ahmadian, M.R.; Cave, H.; Tartaglia, M.; Zenker, M.

    2017-01-01

    RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly

  5. Characterization of Canine parvovirus 2 variants circulating in Greece.

    Science.gov (United States)

    Ntafis, Vasileios; Xylouri, Eftychia; Kalli, Iris; Desario, Costantina; Mari, Viviana; Decaro, Nicola; Buonavoglia, Canio

    2010-09-01

    The aim of the present study was to characterize Canine parvovirus 2 (CPV-2) variants currently circulating in Greece. Between March 2008 and March 2009, 167 fecal samples were collected from diarrheic dogs from different regions of Greece. Canine parvovirus 2 was detected by standard polymerase chain reaction, whereas minor groove binder probe assays were used to distinguish genetic variants and discriminate between vaccine and field strains. Of 84 CPV-2-positive samples, 81 CPV-2a, 1 CPV-2b, and 2 CPV-2c were detected. Vaccine strains were not detected in any sample. Sequence analysis of the VP2 gene of the 2 CPV-2c viruses revealed up to 100% amino acid identity with the CPV-2c strains previously detected in Europe. The results indicated that, unlike other European countries, CPV-2a remains the most common variant in Greece, and that the CPV-2c variant found in Europe is also present in Greece.

  6. COMPARISON OF THE TEST VARIANTS IN ENTRANCE EXAMINATIONS

    Directory of Open Access Journals (Sweden)

    KLŮFA, Jindřich

    2016-12-01

    Full Text Available The paper contains an analysis of the differences of number of points in the test in mathematics between test variants, which were used in the entrance examinations at the Faculty of Business Administration at University of Economics in Prague in 2015. The differences may arise due to the varying difficulty of variants for students, but also because of the different level of knowledge of students who write these variants. This problem we shall study in present paper. The aim of this paper is to study dependence of the results of entrance examinations in mathematics on test variants. The results obtained will be used for further improvement of the admission process at University of Economics.

  7. Reversion in variants from a duplication strain of Aspergillus nidulans

    International Nuclear Information System (INIS)

    Menezes, E.M.; Azevedo, J.L.

    1978-01-01

    Strains of Aspergillus nidulans with a chromosome segment in duplicate, one in normal position and one translocated to another chromosome, are unstable at mitosis. In addition to variants which result from deletions in either of the duplicate segments, which usually have improved morphology, they produce variants with deteriorated morphology. Three deteriorated variants reverted frequently to parental type morphology, both spontaneously and after ultra-violet treatment. Of six reversions analysed genetically, five were due to suppressors and one was probably due to back mutation. The suppressors segregated as single genes and were not linked to the mutation which they suppress. The instability of these so-called 'deteriorated' variants is discussed in relation to mitotic instability phenomena in A. nidulans. (orig.) [de

  8. Protein variants in Hiroshima and Nagasaki: tales of two cities.

    Science.gov (United States)

    Neel, J V; Satoh, C; Smouse, P; Asakawa, J; Takahashi, N; Goriki, K; Fujita, M; Kageoka, T; Hazama, R

    1988-12-01

    The results of 1,465,423 allele product determinations based on blood samples from Hiroshima and Nagasaki, involving 30 different proteins representing 32 different gene products, are analyzed in a variety of ways, with the following conclusions: (1) Sibships and their parents are included in the sample. Our analysis reveals that statistical procedures designed to reduce the sample to equivalent independent genomes do not in population comparisons compensate for the familial cluster effect of rare variants. Accordingly, the data set was reduced to one representative of each sibship (937,427 allele products). (2) Both chi 2-type contrasts and a genetic distance measure (delta) reveal that rare variants (P less than .01) are collectively as effective as polymorphisms in establishing genetic differences between the two cities. (3) We suggest that rare variants that individually exhibit significant intercity differences are probably the legacy of tribal private polymorphisms that occurred during prehistoric times. (4) Despite the great differences in the known histories of the two cities, both the overall frequency of rare variants and the number of different rare variants are essentially identical in the two cities. (5) The well-known differences in locus variability are confirmed, now after adjustment for sample size differences for the various locus products; in this large series we failed to detect variants at only three of 29 loci for which sample size exceeded 23,000. (6) The number of alleles identified per locus correlates positively with subunit molecular weight. (7) Loci supporting genetic polymorphisms are characterized by more rare variants than are loci at which polymorphisms were not encountered. (8) Loci whose products do not appear to be essential for health support more variants than do loci the absence of whose product is detrimental to health. (9) There is a striking excess of rare variants over the expectation under the neutral mutation

  9. Family studies to find rare high risk variants in migraine.

    Science.gov (United States)

    Hansen, Rikke Dyhr; Christensen, Anne Francke; Olesen, Jes

    2017-12-01

    Migraine has long been known as a common complex disease caused by genetic and environmental factors. The pathophysiology and the specific genetic susceptibility are poorly understood. Common variants only explain a small part of the heritability of migraine. It is thought that rare genetic variants with bigger effect size may be involved in the disease. Since migraine has a tendency to cluster in families, a family approach might be the way to find these variants. This is also indicated by identification of migraine-associated loci in classical linkage-analyses in migraine families. A single migraine study using a candidate-gene approach was performed in 2010 identifying a rare mutation in the TRESK potassium channel segregating in a large family with migraine with aura, but this finding has later become questioned. The technologies of next-generation sequencing (NGS) now provides an affordable tool to investigate the genetic variation in the entire exome or genome. The family-based study design using NGS is described in this paper. We also review family studies using NGS that have been successful in finding rare variants in other common complex diseases in order to argue the promising application of a family approach to migraine. PubMed was searched to find studies that looked for rare genetic variants in common complex diseases through a family-based design using NGS, excluding studies looking for de-novo mutations, or using a candidate-gene approach and studies on cancer. All issues from Nature Genetics and PLOS genetics 2014, 2015 and 2016 (UTAI June) were screened for relevant papers. Reference lists from included and other relevant papers were also searched. For the description of the family-based study design using NGS an in-house protocol was used. Thirty-two successful studies, which covered 16 different common complex diseases, were included in this paper. We also found a single migraine study. Twenty-three studies found one or a few family specific

  10. Variants at the 9p21 locus and melanoma risk

    International Nuclear Information System (INIS)

    Maccioni, Livia; Rachakonda, Pandur