bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the impact of the screening programme for colorectal cancer in the UK
Authors: Parkin D M , Tappenden P , Olsen A H , Patnick J , Sasieni P 
Published: December 2008

Objectives Screening for colorectal cancer by biennial testing for faecal occult blood is being introduced in the UK from 2007. We examine the likely impact of the programme, in terms of reduced mortality, lives saved and changes in incidence, over the next 20 years. Setting Projections of incidence and mortality of colorectal cancer in England, and the policy that has been adopted for screening in England (biennial at ages 60–69 from 2007, then 60–74 in 2010). Methods The results are based on the output of a simulation model that has been used to examine cost-effectiveness of screening policy options, with two scenarios regarding compliance with screening; both assume that 20% of the population will never attend for screening, but attendance of those who do is modelled either as a random 60% or 80%, at each screening round. Results The decrease in mortality rates expected 20 years after introducing screening is 13–17% in men and 12–15% in women (depending on the attendance levels). The model predicts an initial rise in incidence, followed (after six to seven years) by a fall, so that there is little net change in the number of cases detected over a 20-year period. Conclusion Percentage changes in mortality seem modest, but the projected saving in terms of numbers of lives is not negligible – 1800–2400 per year by 2025 in England (equivalent numbers are 2200–2700 in all over the UK). Newer screening modalities may improve on these projected results.
Cost evaluation in a colorectal cancer screening programme by faecal occult blood test in the District of Florence
Authors: Grazzini Grazia , Ciatto Stefano , Cislaghi Cesare , Castiglione Guido , Falcone Manuele , Mantellini Paola , Zappa Marco ,   The Working Group of Regional Reference Centre for Oncological Screening of Tuscany
Published: December 2008

Objectives To evaluate the direct costs of first and repeat colorectal cancer screening by immunochemical faecal occult blood testing (I-FOBT). Methods Florence district residents aged 50–70 were invited to undergo one-time I-FOBT every two years. Full colonoscopy was recommended for FOBT-positive subjects. Direct cost analysis was carried out separately for the first and repeat screening. All relevant resources consumed by the programme were calculated. Results Among 25,428 or 62,369 subjects invited to the first or repeat screening, respectively, the corresponding participation rate was 47.8% or 52.3%, and the positivity rate was 4.4% and 3.3%. Corresponding detection rates and positive predictive values for cancer and advanced adenoma were 11.3% or 8.9% and 32.4% or 32.8%, respectively. The assessment phase accounted for the major cost, as compared with recruitment and screening. All cost indicators were slightly higher in the first screening compared with repeat screening. Cost per cancer and advanced adenoma detected was similar in the first or repeat screening. A higher than observed participation rate would have substantially reduced screening cost. Conclusion Analysis of I-FOBT-organized population-based screening cost demonstrates lower cost at repeat compared with first screening and provides reference for decision-making in screening implementation.
Automated imaging of circulating fluorocytes for the diagnosis of erythropoietic protoporphyria: a pilot study for population screening
Authors: Lau Kin-Chong , Lam Ching-Wan 
Published: December 2008

Objectives To improve the traditional fresh blood film method to a high-throughput analysis of the presence of circulating fluorescent red cells (fluorocytes) in erythropoietic protoporphyria (EPP) using an automated imaging system. Methods Based on the autofluorescence of protoporphyrin, we used an automatic image acquisition platform for examining fluorocytes in peripheral blood with minimal sample preparation. The image acquisition is easy-to-use under automated operations of excitation, focusing, detection and data analysis. Quality image and semi-quantitative fluorescence measurement of fluorocytes can be generated in a single step. For high-throughput analysis, the platform can image more than 200 96-well micro-plates, i.e. 19200 samples, in approximately 10 hours. Importantly, the reagent cost of analysis is negligible. Results In this pilot study, three EPP patients were diagnosed and 4000 normal individuals were screened for EPP by this method. Our results showed that the method can distinguish the overt case and asymptomatic carriers. It gives reliable evidence for rapid EPP screening. Conclusion This automated imaging system provides multiple advantages that improve the traditional fresh blood film method as a more effective diagnostic tool and facilitates population screening for EPP. As fluorocytes are present in the umbilical cord blood of EPP patients, this high-throughput method can be potentially used for newborn screening of EPP.
First trimester Down's syndrome screening marker values and cigarette smoking: new data and a meta-analysis on free β human chorionic gonadotophin, pregnancy-associated plasma protein-A and nuchal translucency
Authors: Bestwick Jonathan P , Huttly Wayne J , Wald Nicholas J 
Published: December 2008

Objectives To examine the effect of smoking on three first trimester screening markers for Down's syndrome that constitute the Combined test, namely nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A) and free β human chorionic gonadotophin (free β-hCG) and to use the results to determine which of these markers need to be adjusted for smoking and by how much. Methods The difference in the median multiple of the median (MoM) values in smokers compared to non-smokers was determined for NT, PAPP-A and free β-hCG in 12,517 unaffected pregnancies that had routine first trimester Combined test screening. These results were then included in a meta-analysis of published studies and the effect of adjusting for smoking on screening performance of the Combined test was estimated. Results The results using the routine screening data were similar to the summary estimates from the meta-analysis of all studies. The results from the meta-analysis were; median MoM in smokers compared to non-smokers: 1.06 NT (95% confidence interval 1.03 to 1.10), 0.81 PAPP-A (0.80 to 0.83) and 0.94 free β-hCG (0.89 to 0.99). The effect of adjusting for smoking on the Combined test is small, with an estimated less than half percentage point increase in the detection rate (the proportion of affected pregnancies with a positive result) for a 3% false-positive rate (the proportion of unaffected pregnancies with a positive result) and less than 0.2 percentage point decrease in the false-positive rate for an 85% detection rate. Conclusion Adjusting first trimester screening markers for smoking has a minimal favourable effect on screening performance, but it is simple to implement and this paper provides the adjustment factors needed if a decision is made to make such an adjustment.
Impact of changing from annual to biennial mammographic screening on breast cancer outcomes in women aged 50–79 in British Columbia
Authors: Coldman Andrew J , Phillips Norm , Olivotto Ivo A , Gordon Paula , Warren Linda , Kan Lisa 
Published: December 2008

Objectives The objective of this study was to compare breast cancer outcomes among women subject to different policies on mammography screening frequency. Setting Data were obtained for women participating in the Screening Mammography Programme of British Columbia (SMPBC) for 1988–2005. The SMPBC changed its policy for women aged 50–79 years from annual to biennial mammography in 1997, but retained an annual recommendation for women aged 40–49 years. Methods Breast cancer outcomes were compared for women participating in the programme before and after 1997 for two groups: ages 40–49 and 50–79 years. Results There were data on 658,151 women. Comparing pre-1997 and post-1997, the median interscreen interval increased by 11.1 months in women 50–79 but by only 0.3 months in women aged 40–49. Excluding those detected at initial screen, 6291 breast cancers were identified. Comparing pre-1997 and post-1997: the relative rates (RR) of screen detected cancer increased in women aged 40–49 (RR = 1.32) and the rate of invasive cancers ≥20 mm at diagnosis decreased (RR = 0.83); the rate of cancers with axillary node involvement increased in women aged 50–79 (RR = 1.23). Cancer survival improved after 1997 for women diagnosed at ages 40–49 (hazard ratio = 0.62), but was unchanged for women aged 50–79. Breast cancer mortality rates did not change between the periods in either age group. Conclusion The proximal cancer outcomes considered (staging and survival) improved in women aged 40–49 but this was offset in women aged 50–79 associated with the change in screen frequency. These changes did not result in alterations in breast cancer mortality rates in either age group.
Normal endometrial cells in cervical cytology: systematic review of prevalence and relation to significant endometrial pathology
Authors: Canfell Karen , Kang Yoon Jung , Clements Mark , Moa Aye Myat , Beral Valerie 
Published: December 2008

Objectives To estimate the prevalence of normal endometrial cells (NECs) and the proportion of NECs associated with significant endometrial pathology in conventional and liquid-based cytology (LBC) cervical smears; and to assess the association between NECs and clinical symptoms in women with endometrial hyperplasia or carcinoma. Methods Systematic review of the literature and meta-analysis of prevalence and proportion data. The review was confined to studies reporting on NECs in smears from postmenopausal women or women aged 40+. Results A total of 22 relevant primary studies were identified from 1970 to 2007. The overall summary estimate for the prevalence of NECs in smears from postmenopausal women or women aged 40+ in all screening smears was 0.4% (95% CI 0.2–0.7%); this was 0.3% (95% CI 0.1–0.5%) and 0.9% (95% CI 0.5–1.4%) for conventional and LBC smears, respectively; P = 0.003 for difference. The overall estimate for the proportion of NECs associated with significant endometrial pathology was 7% (95% CI 4–10%); this was 11% (95% CI 8–14%) and 2% (95% CI 1–2%) for conventional and LBC smears, respectively; P < 0.001 for difference. In women with significant endometrial pathology, the presence of NECs in followed-up women was associated with abnormal uterine bleeding in 79% (95% CI 68–87%) of cases. Conclusion Compared with conventional cytology, LBC may be associated with a higher prevalence of NECs but these are less likely to be associated with endometrial pathology. This finding might be explained by more consistent use of sampling instruments for LBC with better access to the endocervical canal or alternatively by changes over time, broadly coincident with the introduction of LBC, in the population in which NECs are reported. In followed-up women with NECs, most endometrial pathology is accompanied by symptoms, implying that a relatively smaller number of additional cases are identified through follow-up of asymptomatic women.
Accurate Determination of Surface Heat Fluxes During Quenching Characterized by Boiling Water Heat Transfer
Authors: Wells M. A. , Daun K. J. 
Published: December 2008

Abstract
Mathematical models play a critical role in design, optimization, and control of water quenching treatment in metals processing. Modeling these processes correctly is predicated on accurately characterizing the heat transfer at the product surface throughout the quench operation, usually with a boiling curve. These curves are most often generated from time-resolved subsurface temperature measurements carried out during quenching, although data analysis is complicated by the ill-posed nature of the underlying problem. This paper reviews the best experimental and analytical practices that have been developed for recovering the boiling water curve through an inverse heat conduction analysis.
A Model Selection Approach for the Identification of Quantitative Trait Loci in Experimental Crosses, Allowing Epistasis
Authors: Manichaikul Ani , Moon Jee Young , Sen Śaunak , Yandell Brian S , Broman Karl W 
Published: December 2008

AbstractThe identification of quantitative trait loci (QTL) and their interactions is a crucial step toward the discovery of genes responsible for variation in experimental crosses. The problem is best viewed as one of model selection, and the most important aspect of the problem is the comparison of models of different sizes. We present a penalized likelihood approach, with penalties on QTL and pairwise interactions chosen to control false positive rates. This extends the work of Broman and Speed to allow for pairwise interactions among QTL. A conservative version of our penalized LOD score provides strict control over the rate of extraneous QTL and interactions; a more liberal criterion is more lenient on interactions but seeks to maintain control over the rate of inclusion of false loci. The key advance is that one needs only to specify a target false positive rate rather than a prior on the number of QTL and interactions. We illustrate the use of our model selection criteria as exploratory tools; simulation studies demonstrate reasonable power to detect QTL. Our liberal criterion is comparable in power to two Bayesian approaches.
Multilocus Patterns of Nucleotide Diversity, Population Structure and Linkage Disequilibrium inBoechera stricta, a Wild Relative of Arabidopsis
Authors: Song Bao-Hua , Windsor Aaron J , Schmid Karl J , Ramos-Onsins Sebastian , Schranz M Eric , Heidel Andrew J , Mitchell-Olds Thomas 
Published: December 2008

AbstractInformation about polymorphism, population structure, and linkage disequilibrium (LD) is crucial for association studies of complex trait variation. However, most genomewide studies have focused on model systems, with very few analyses of undisturbed natural populations. Here, we sequenced 86 mapped nuclear loci for a sample of 46 genotypes of Boechera stricta and two individuals of B. holboellii, both wild relatives of Arabidopsis. Isolation by distance was significant across the species range of B. stricta, and three geographic groups were identified by structure analysis, principal coordinates analysis, and distance-based phylogeny analyses. The allele frequency spectrum indicated a genomewide deviation from an equilibrium neutral model, with silent nucleotide diversity averaging 0.004. LD decayed rapidly, declining to background levels in ∼10 kb or less. For tightly linked SNPs separated by &lt;1 kb, LD was dependent on the reference population. LD was lower in the specieswide sample than within populations, suggesting that low levels of LD found in inbreeding species such as B. stricta, Arabidopsis thaliana, and barley may result from broad geographic sampling that spans heterogeneous genetic groups. Finally, analyses also showed that inbreeding B. stricta and A. thaliana have ∼45% higher recombination per kilobase than outcrossing A. lyrata.
Thea2Mating-Type Locus Geneslga2andrga2Direct Uniparental Mitochondrial DNA (mtDNA) Inheritance and Constrain mtDNA Recombination During Sexual Development ofUstilago maydis
Authors: Fedler Michael , Luh Kai-Stephen , Stelter Kathrin , Nieto-Jacobo Fernanda , Basse Christoph W 
Published: December 2008

AbstractUniparental inheritance of mitochondria dominates among sexual eukaryotes. However, little is known about the mechanisms and genetic determinants. We have investigated the role of the plant pathogen Ustilago maydis genes lga2 and rga2 in uniparental mitochondrial DNA (mtDNA) inheritance during sexual development. The lga2 and rga2 genes are specific to the a2 mating-type locus and encode small mitochondrial proteins. On the basis of identified sequence polymorphisms due to variable intron numbers in mitochondrial genotypes, we could demonstrate that lga2 and rga2 decisively influence mtDNA inheritance in matings between a1 and a2 strains. Deletion of lga2 favored biparental inheritance and generation of recombinant mtDNA molecules in combinations in which inheritance of mtDNA of the a2 partner dominated. Conversely, deletion of rga2 resulted in predominant loss of a2-specific mtDNA and favored inheritance of the a1 mtDNA. Furthermore, expression of rga2 in the a1 partner protected the associated mtDNA from elimination. Our results indicate that Lga2 in conjunction with Rga2 directs uniparental mtDNA inheritance by mediating loss of the a1-associated mtDNA. This study shows for the first time an interplay of mitochondrial proteins in regulating uniparental mtDNA inheritance.
Mutations in the Chromosomal Passenger Complex and the Condensin Complex Differentially Affect Synaptonemal Complex Disassembly and Metaphase I Configuration in Drosophila Female Meiosis
Authors: Resnick Tamar D , Dej Kimberley J , Xiang Youbin , Hawley R Scott , Ahn Caroline , Orr-Weaver Terry L 
Published: December 2008

AbstractProduction of haploid gametes relies on the specially regulated meiotic cell cycle. Analyses of the role of essential mitotic regulators in meiosis have been hampered by a shortage of appropriate alleles in metazoans. We characterized female-sterile alleles of the condensin complex component dcap-g and used them to define roles for condensin in Drosophila female meiosis. In mitosis, the condensin complex is required for sister-chromatid resolution and contributes to chromosome condensation. In meiosis, we demonstrate a role for dcap-g in disassembly of the synaptonemal complex and for proper retention of the chromosomes in a metaphase I-arrested state. The chromosomal passenger complex also is known to have mitotic roles in chromosome condensation and is required in some systems for localization of the condensin complex. We used the QA26 allele of passenger component incenp to investigate the role of the passenger complex in oocyte meiosis. Strikingly, in incenpQA26 mutants maintenance of the synaptonemal complex is disrupted. In contrast to the dcap-g mutants, the incenp mutation leads to a failure of paired homologous chromosomes to biorient, such that bivalents frequently orient toward only one pole in prometaphase and metaphase I. We show that incenp interacts genetically with ord, suggesting an important functional relationship between them in meiotic chromosome dynamics. The dcap-g and incenp mutations cause maternal effect lethality, with embryos from mutant mothers arrested in the initial mitotic divisions.
Characterization of Demographic Expansions From Pairwise Comparisons of Linked Microsatellite Haplotypes
Authors: Navascués Miguel , Hardy Olivier J , Burgarella Concetta 
Published: December 2008

Abstract
This work extends the methods of demographic inference based on the distribution of pairwise genetic differences between individuals (mismatch distribution) to the case of linked microsatellite data. Population genetics theory describes the distribution of mutations among a sample of genes under different demographic scenarios. However, the actual number of mutations can rarely be deduced from DNA polymorphisms. The inclusion of mutation models in theoretical predictions can improve the performance of statistical methods. We have developed a maximum-pseudolikelihood estimator for the parameters that characterize a demographic expansion for a series of linked loci evolving under a stepwise mutation model. Those loci would correspond to DNA polymorphisms of linked microsatellites (such as those found on the Y chromosome or the chloroplast genome). The proposed method was evaluated with simulated data sets and with a data set of chloroplast microsatellites that showed signal for demographic expansion in a previous study. The results show that inclusion of a mutational model in the analysis improves the estimates of the age of expansion in the case of older expansions.
Nitrogen Catabolite Repression-Sensitive Transcription as a Readout of Tor Pathway Regulation: The Genetic Background, Reporter Gene and GATA Factor Assayed Determine the Outcomes
Authors: Georis Isabelle , Feller André , Tate Jennifer J , Cooper Terrance G , Dubois Evelyne 
Published: December 2008

Abstract
Nitrogen catabolite repression (NCR)-sensitive genes, whose expression is highly repressed when provided with excess nitrogen and derepressed when nitrogen is limited or cells are treated with rapamycin, are routinely used as reporters in mechanistic studies of the Tor signal transduction pathway in Saccharomyces cerevisiae. Two GATA factors, Gln3 and Gat1, are responsible for NCR-sensitive transcription, but recent evidence demonstrates that Tor pathway regulation of NCR-sensitive transcription bifurcates at the level of GATA factor localization. Gln3 requires Sit4 phosphatase for nuclear localization and NCR-sensitive transcription while Gat1 does not. In this article, we demonstrate that the extent to which Sit4 plays a role in NCR-sensitive transcription depends upon whether or not (i) Gzf3, a GATA repressor homologous to Dal80, is active in the genetic background assayed; (ii) Gat1 is able to activate transcription of the assayed gene in the absence of Gln3 in that genetic background; and (iii) the gene chosen as a reporter is able to be transcribed by Gln3 or Gat1 in the absence of the other GATA factor. Together, the data indicate that in the absence of these three pieces of information, overall NCR-sensitive gene transcription data are unreliable as Tor pathway readouts.
Donor Blood Glucose 6-Phosphate Dehydrogenase Deficiency Reduces the Efficacy of Exchange Transfusion in Neonatal Hyperbilirubinemia
Authors: Samanta Sandip , Kumar Praveen , Kishore Sai Sunil , Garewal Gurjeewan , Narang Anil 
Published: December 2008

OBJECTIVES. Acute intravascular hemolysis after exchange transfusion with glucose 6-phosphate dehydrogenase–deficient blood has been reported; however, it is not routine to screen donor blood for glucose 6-phosphate dehydrogenase deficiency while performing exchange transfusion. We hypothesized that exchange transfusion with glucose 6-phosphate dehydrogenase–deficient blood would lead to a less-than-expected decrease in total serum bilirubin. The objective of this study was to evaluate the effect of exchange transfusion with glucose 6-phosphate dehydrogenase–deficient blood in neonates with idiopathic hyperbilirubinemia on postexchange total serum bilirubin levels, duration of phototherapy, and need for repeat exchange transfusions.
METHODS. All neonates who were undergoing exchange transfusion for idiopathic hyperbilirubinemia were enrolled. A sample of donor blood was collected at the time of exchange transfusion for a glucose 6-phosphate dehydrogenase assay. The standard criteria for starting and stopping phototherapy and exchange transfusion were applied.
RESULTS. During the 1-year study period, 21 infants underwent exchange with glucose 6-phosphate dehydrogenase–deficient blood, and 114 neonates with similar baseline characteristics underwent exchange transfusion with glucose 6-phosphate dehydrogenase–normal blood. From 6 to 60 hours after exchange transfusion, there was a significantly lesser drop in total serum bilirubin in the recipients of glucose 6-phosphate dehydrogenase–deficient donor blood compared with recipients of glucose 6-phosphate dehydrogenase–normal blood. The mean duration of phototherapy in the postexchange period and number of infants who underwent repeat exchange transfusions were significantly higher in recipients of glucose 6-phosphate dehydrogenase–deficient donor blood in comparison with control subjects. Concurrently, there was a significantly higher drop in hematocrit and rise in plasma hemoglobin in the glucose 6-phosphate dehydrogenase–deficient donor group.
CONCLUSIONS. Exchange transfusion with glucose 6-phosphate dehydrogenase–deficient donor blood leads to a lesser drop in postexchange total serum bilirubin. It prolongs the duration of phototherapy and increases the need for repeat exchange transfusions.