bluuebunny/crossref_metadata_2025 huggingface dataset:
Extensive purifying selection acting on synonymous sites in HIV-1 Group M sequences
Authors: Ngandu Nobubelo K , Scheffler Konrad , Moore Penny , Woodman Zenda , Martin Darren , Seoighe Cathal
Published: December 2008

Background

Positive selection pressure acting on protein-coding sequences is usually inferred when the rate of nonsynonymous substitution is greater than the synonymous rate. However, purifying selection acting directly on the nucleotide sequence can lower the synonymous substitution rate. This could result in false inference of positive selection because when synonymous changes at some sites are under purifying selection, the average synonymous rate is an underestimate of the neutral rate of evolution. Even though HIV-1 coding sequences contain a number of regions that function at the nucleotide level, and are thus likely to be affected by purifying selection, studies of positive selection assume that synonymous substitutions can be used to estimate the neutral rate of evolution.

Results

We modelled site-to-site variation in the synonymous substitution rate across coding regions of the HIV-1 genome. Synonymous substitution rates were found to vary significantly within and between genes. Surprisingly, regions of the genome that encode proteins in more than one frame had significantly higher synonymous substitution rates than regions coding in a single frame. We found evidence of strong purifying selection pressure affecting synonymous mutations in fourteen regions with known functions. These included an exonic splicing enhancer, the rev-responsive element, the poly-purine tract and a transcription factor binding site. A further five highly conserved regions were located within known functional domains. We also found four conserved regions located in env and vpu which have not been characterized previously.

Conclusion

We provide the coordinates of genomic regions with markedly lower synonymous substitution rates, which are putatively under the influence of strong purifying selection pressure at the nucleotide level as well as regions encoding proteins in more than one frame. These regions should be excluded from studies of positive selection acting on HIV-1 coding regions.
The inhibition of assembly of HIV-1 virus-like particles by 3-O-(3',3'-dimethylsuccinyl) betulinic acid (DSB) is counteracted by Vif and requires its Zinc-binding domain
Authors: DaFonseca Sandrina , Coric Pascale , Gay Bernard , Hong Saw See , Bouaziz Serge , Boulanger Pierre
Published: December 2008

Background

DSB, the 3-O-(3',3'dimethylsuccinyl) derivative of betulinic acid, blocks the last step of protease-mediated processing of HIV-1 Gag precursor (Pr55Gag), which leads to immature, noninfectious virions. When administered to Pr55Gag-expressing insect cells (Sf9), DSB inhibits the assembly and budding of membrane-enveloped virus-like particles (VLP). In order to explore the possibility that viral factors could modulate the susceptibility to DSB of the VLP assembly process, several viral proteins were coexpressed individually with Pr55Gag in DSB-treated cells, and VLP yields assayed in the extracellular medium.

Results

Wild-type Vif (Vifwt) restored the VLP production in DSB-treated cells to levels observed in control, untreated cells. DSB-counteracting effect was also observed with Vif mutants defective in encapsidation into VLP, suggesting that packaging and anti-DSB effect were separate functions in Vif. The anti-DSB effect was abolished for VifC133S and VifS116V, two mutants which lacked the zinc binding domain (ZBD) formed by the four H108C114C133H139coordinates with a Zn atom. Electron microscopic analysis of cells coexpressing Pr55Gag and Vifwtshowed that a large proportion of VLP budded into cytoplasmic vesicles and were released from Sf9 cells by exocytosis. However, in the presence of mutant VifC133S or VifS116V, most of the VLP assembled and budded at the plasma membrane, as in control cells expressing Pr55Gag alone.

Conclusion

The function of HIV-1 Vif protein which negated the DSB inhibition of VLP assembly was independent of its packaging capability, but depended on the integrity of ZBD. In the presence of Vifwt, but not with ZBD mutants VifC133S and VifS116V, VLP were redirected to a vesicular compartment and egressed via the exocytic pathway.
Voxel-based structural magnetic resonance imaging (MRI) study of patients with early onset schizophrenia
Authors: Yoshihara Yujiro , Sugihara Genichi , Matsumoto Hideo , Suckling John , Nishimura Katsuhiko , Toyoda Takao , Isoda Haruo , Tsuchiya Kenji J , Takebayashi Kiyokazu , Suzuki Katsuaki , Sakahara Harumi , Nakamura Kazuhiko , Mori Norio , Takei Nori
Published: December 2008

Background

Investigation into the whole brain morphology of early onset schizophrenia (EOS) to date has been sparse. We studied the regional brain volumes in EOS patients, and the correlations between regional volume measures and symptom severity.

Methods

A total of 18 EOS patients (onset under 16 years) and 18 controls matched for age, gender, parental socioeconomic status, and height were examined. Voxel-based morphometric analysis using the Brain Analysis Morphological Mapping (BAMM) software package was employed to explore alterations of the regional grey (GM) and white matter (WM) volumes in EOS patients. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).

Results

EOS patients had significantly reduced GM volume in the left parahippocampal, inferior frontal, and superior temporal gyri, compared with the controls. They also had less WM volume in the left posterior limb of the internal capsule and the left inferior longitudinal fasciculus. The positive symptom score of PANSS (higher values corresponding to more severe symptoms) was negatively related to GM volume in the bilateral posterior cingulate gyrus. The negative symptom score was positively correlated with GM volume in the right thalamus. As for the association with WM volume, the positive symptom score of PANSS was positively related to cerebellar WM (vermis region), and negatively correlated with WM in the brain stem (pons) and in the bilateral cerebellum (hemisphere region).

Conclusion

Our findings of regional volume alterations of GM and WM in EOS patients coincide with those of previous studies of adult onset schizophrenia patients. However, in brain regions that had no overall structural differences between EOS patients and controls (that is, the bilateral posterior cingulate gyrus, the right thalamus, the cerebellum, and the pons), within-subject analysis of EOS patients alone revealed that there were significant associations of the volume in these areas and the symptom severity. These findings suggest that at an early stage of the illness, especially for those with onset before brain maturation, a wide range of disturbed neural circuits, including these brain regions that show no apparent morphological changes, may contribute to the formation of the symptomatology.
Essential operating principles for tumor spheroid growth
Authors: Engelberg Jesse A , Ropella Glen EP , Hunt C Anthony
Published: December 2008

Background

Our objective was to discover in silico axioms that are plausible representations of the operating principles realized during characteristic growth of EMT6/Ro mouse mammary tumor spheroids in culture. To reach that objective we engineered and iteratively falsified an agent-based analogue of EMT6 spheroid growth. EMT6 spheroids display consistent and predictable growth characteristics, implying that individual cell behaviors are tightly controlled and regulated. An approach to understanding how individual cell behaviors contribute to system behaviors is to discover a set of principles that enable abstract agents to exhibit closely analogous behaviors using only information available in an agent's immediate environment. We listed key attributes of EMT6 spheroid growth, which became our behavioral targets. Included were the development of a necrotic core surrounded by quiescent and proliferating cells, and growth data at two distinct levels of nutrient.

Results

We then created an analogue made up of quasi-autonomous software agents and an abstract environment in which they could operate. The system was designed so that upon execution it could mimic EMT6 cells forming spheroids in culture. Each agent used an identical set of axiomatic operating principles. In sequence, we used the list of targeted attributes to falsify and revise these axioms, until the analogue exhibited behaviors and attributes that were within prespecified ranges of those targeted, thereby achieving a level of validation.

Conclusion

The finalized analogue required nine axioms. We posit that the validated analogue's operating principles are reasonable representations of those utilized by EMT6/Ro cells during tumor spheroid development.
Is there an association between fibromyalgia and below-normal levels of urinary cortisol?
Authors: Izquierdo–Álvarez Silvia , Bocos–Terraz Julia Pilar , Bancalero–Flores Jose Luis , Pavón–Romero Lenin , Serrano–Ostariz Enrique , de Miquel Cayetano Alegre
Published: December 2008

Background

Adynamia in fibromyalgia (FM) may be an expression of a functional deficit of the hypothalamic-pituitary-adrenal axis and be associated with below-normal levels of urinary cortisol. Our aim was to demonstrate that urinary cortisol was lower in patients with FM than in healthy subjects.

Findings

We measured urinary cortisol levels for a sample of 47 women aged 29 to 64 years (mean age 53 years), diagnosed with FM 2–3 years previously, and compared the results with those for a control sample of 58 healthy women of a similar age. Samples of 24-hour urine were appropriately collected and levels of urinary cortisol were measured using the fluorescence polarization immunoassay method. The mean cortisol value for the women with FM was 65.40 ± 27.10 μg/L, significantly lower than the mean cortisol level for the control group, at 90.83 ± 38.17 μg/L (p < 0.001).

Conclusion

Our study confirms that women with FM have significantly lower urinary cortisol levels than healthy women.
Long-Term Benefit of High-Dose Epirubicin in Adjuvant Chemotherapy for Node-Positive Breast Cancer: 15-Year Efficacy Results of the Belgian Multicentre Study
Authors: de Azambuja Evandro , Paesmans Marianne , Beauduin Marc , Vindevoghel Anita , Cornez Nathalie , Finet Claude , Ries Fernand , Closon-Dejardin Marie Thérèse , Kerger Joseph , Gobert Philippe , Focan Christian , Tagnon Alain , Dolci Stella , Nogaret Jean M. , di Leo Angelo , Piccart-Gebhart Martine J.
Published: December 2008

Purpose

The 4-year results of this trial demonstrated that a higher dose of epirubicin with cyclophosphamide (HEC) is superior to a lower dose of epirubicin, 60 mg/m2 (EC), for event-free survival (EFS; 27% reduction), but is not superior to classical oral cyclophosphamide, methotrexate, and fluorouracil (CMF) in the adjuvant treatment of node-positive breast cancer. Herein we report the 15-year data on efficacy and long-term toxicity of this three-arm Belgian multicenter trial.

Patients and Methods

Between March 1988 and December 1996, 777 eligible patients were randomly assigned to six cycles of CMF, eight cycles of EC, or eight cycles HEC.

Results

The 15-year EFS was 45% for patients who received CMF, 39% for patients who received EC, and 50% for patients who received HEC. The hazard ratios (HR) were 0.77 for HEC versus EC (95% CI, 0.60 to 0.98; P = .03), 0.90 for HEC versus CMF (P = .39), and 0.86 for EC versus CMF (P = .21). No difference in overall survival (OS) was seen. Cardiac toxicity was more frequent with HEC than with CMF (11 patients v 1 patient; P = .006), but no more than with EC (P = .21).

Conclusion

Treatment with HEC demonstrated superior EFS when compared with lower-dose epirubicin. However, we do not recommend the use of HEC regimen in daily clinical practice, mainly because of the higher risk of cardiotoxicity related to the cumulative doses of epirubicin and the lack of superiority of anthracyclines over CMF in our study.
Trends in Racial and Age Disparities in Definitive Local Therapy of Early-Stage Breast Cancer
Authors: Freedman Rachel A. , He Yulei , Winer Eric P. , Keating Nancy L.
Published: December 2008

Purpose

Guidelines recommend breast-conserving surgery (BCS) with radiation or mastectomy for definitive local therapy of stage I/II breast cancers. We assessed receipt of definitive local therapy for early-stage breast cancer by race/ethnicity and age and examined trends over time.

Patients and Methods

We calculated rates of definitive local therapy (mastectomy or BCS with radiation) for 375,547 adult women with stage I or II breast cancer diagnosed during 1988 to 2004 using Surveillance, Epidemiology, and End Results registry data. We assessed the probability of definitive local therapy and trends over time using multivariate logistic regression.

Results

Overall, 85.8% of women had definitive local therapy. As mastectomy rates decreased (76.5% in 1988 to 38.0% in 2004; P < .001), definitive local therapy rates also decreased (95.2% in 1988 to 79.2% in 2004; P < .001). In adjusted analyses, rates of definitive local therapy were modestly lower for black and Hispanic (v white) women and higher for Asian women. Differences for black and Asian women were stable over time (P = .61 and P = .35 for interaction), but increased for Hispanic women (P = .0003). Although age differences narrowed over time, women older than 70 years and women ≤ 60 years had lower rates of definitive local therapy than women 61 to 70 years throughout the study period.

Conclusion

As breast conservation has increasingly substituted mastectomy, our findings suggest fewer women are receiving definitive local breast cancer therapy, with persistent disparities for black and Hispanic women as well as women age ≤ 60 and older than 70 years. Interventions to assure receipt of radiation after BCS are needed to eliminate these disparities.
Effect of Recombinant Adenovirus-p53 Combined With Radiotherapy on Long-Term Prognosis of Advanced Nasopharyngeal Carcinoma
Authors: Pan Jian-ji , Zhang Shan-wen , Chen Chuan-beng , Xiao Shao-wen , Sun Yan , Liu Chang-qin , Su Xing , Li Dong-ming , Xu Gang , Xu Bo , Lu You-yong
Published: December 2008

Purpose

To centrally assess the safety, efficacy, and 6-year follow-up of recombinant adenovirus-p53 (rAd-p53) combined with radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC).

Patients and Methods

A randomized controlled clinical study on rAd-p53 combined with RT in 42 patients with NPC was compared with a control group of 40 patients with NPC treated with RT alone. In the group receiving rAd-p53 combined with RT, rAd-p53 was intratumorally injected once a week for 8 weeks. Concurrent RT (70 Gy in 35 fractions) was given to the nasopharyngeal tumor and neck lymph node. Patients and tumors were monitored for adverse events and responses.

Results

rAd-p53–specific p53 mRNA was detected in postinjection of rAd-p53 biopsies from 16 (94.1%) of 17 patients. Upregulation of p21/WAF1 and Bax and downregulation of vascular endothelial growth factor were observed in postinjection tumor biopsy. Complete response rate in the group receiving rAd-p53 combined with RT was observed at 2.73 times that of the group receiving RT alone (66.7% v 24.4%). Six-year follow-up data showed that rAd-p53 significantly increased the 5-year locoregional tumor control rate by 25.3% for patients with NPC treated with irradiation (P = .002). The 5-year overall survival rate and 5-year disease-free survival rate of the group receiving rAd-p53 combined with RT were 7.5% (P = .34) and 11.7% (P = .21) higher than those of the group receiving RT alone. No dose-limiting toxicity or adverse events appeared, except for transient fever after rAd-p53 administration.

Conclusion

In patients with NPC, rAd-p53 was safe and biologically active. Our results indicated that rAd-p53 improves radiotherapeutic tumor control and survival rate in patients with NPC.
Complete Cytoreductive Surgery Plus Intraperitoneal Chemohyperthermia With Oxaliplatin for Peritoneal Carcinomatosis of Colorectal Origin
Authors: Elias Dominique , Lefevre Jérémie H. , Chevalier Julie , Brouquet Antoine , Marchal Frédéric , Classe Jean-Marc , Ferron Gwenaël , Guilloit Jean-Marc , Meeus Pierre , Goéré Diane , Bonastre Julia
Published: December 2008

Purpose

To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC).

Patients and Methods

All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time.

Results

Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test).

Conclusion

Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.
Foci of Listeria monocytogenes persist in the bone marrow
Authors: Hardy Jonathan , Chu Pauline , Contag Christopher H.
Published: December 2008

Murine listeriosis is one of the most comprehensive and well-studied models of infection, and Listeria monocytogenes has provided seminal information regarding bacterial pathogenesis. However, many aspects of the mouse model remain poorly understood, including carrier states and chronic colonization which represent important features of the spectrum of host-pathogen interaction. Bone marrow has recently been shown to harbor L. monocytogenes, which spreads from this location to the central nervous system. Bone could, therefore, be an important chronic reservoir, but this infection is difficult to study because it involves only a few bacteria and the extent of infection cannot be assessed until after the animal is sacrificed. We employed in vivo bioluminescence imaging to localize L. monocytogenes bone infections over time in live mice, revealing that the bacteria grow in discrete foci. These lesions can persist in many locations in the legs of mice and are not accompanied by a histological indication such as granuloma or a neutrophil infiltratate. We demonstrate that highly attenuated hly mutants, which have defective intracellular replication, are capable of prolonged focal infection of the bone marrow for periods of up to several weeks. These results support the recently proposed hypothesis that the bone marrow is a unique niche for L. monocytogenes.
The fission yeast model for the lysosomal storage disorder Batten disease predicts disease severity caused by mutations in CLN3
Authors: Haines Rebecca L. , Codlin Sandra , Mole Sara E.
Published: December 2008

The function of the CLN3 protein, which is mutated in patients with the neurodegenerative lysosomal storage disorder Batten disease, has remained elusive since it was identified 13 years ago. Here, we exploited the Schizosaccharomyces pombe model to gain new insights into CLN3 function. We modelled all missense mutations of CLN3 in the orthologous protein Btn1p, as well as a series of targeted mutations, and assessed trafficking and the ability of the mutant proteins to rescue four distinct phenotypes of btn1Δ cells. Mutating the C-terminal cysteine residues of Btn1p caused it to be internalised into the vacuole, providing further evidence that this protein functions from pre-vacuole compartments. Mutations in the lumenal regions of the multi-spanning membrane protein, especially in the third lumenal domain which contains a predicted amphipathic helix, had the most significant impact on Btn1p function, indicating that these domains of CLN3 are functionally important. Only one mutant protein was able to rescue the cell curving phenotype (p.Glu295Lys), and since this mutation is associated with a very protracted disease progression, this phenotype could be used to predict the disease severity of novel mutations in CLN3. The ability to predict disease phenotypes in S. pombe confirms this yeast as an invaluable tool to understanding Batten disease.
MDM2-A, a common Mdm2 splice variant, causes perinatal lethality, reduced longevity and enhanced senescence
Authors: Volk Erin L. , Schuster Katja , Nemeth Katie M. , Fan Liying , Harris Linda C.
Published: December 2008

MDM2 is the predominant negative regulator of p53 that functions to maintain the appropriate level of expression and activity of this central tumor suppressor. Mdm2-a is a commonly identified splice variant of Mdm2; however, its physiological function is unclear. To gain insight into the activity of MDM2-A and its potential impact on p53, an Mdm2-a transgenic mouse model was generated. Mdm2-a transgenic mice displayed a homozygous-lethal phenotype that could be rescued by a reduction in p53 expression, demonstrating a dependence upon p53. Mdm2-a hemizygous mice exhibited reduced longevity, and enhanced senescence was observed in their salivary glands. In addition, the transgenic mice lacked typical, accelerated aging phenotypes. Growth of transgenic mouse embryonic fibroblasts (MEFs) was inhibited relative to wild-type MEFs, and MDM2-A was shown to bind to full-length MDM2 in an interaction that could increase p53 activity via reduced MDM2 inhibition. Evidence of p53 activation was shown in the Mdm2-a transgenic MEFs, including p53-dependent growth inhibition and elevated expression of the p53 target protein p21. In addition, MDM2-A increased senescence in a p21-independent manner. In conclusion, unexpected roles for MDM2-A in longevity and senescence were identified in a transgenic mouse model, suggesting that Mdm2 splice variants might be determinants of these phenotypes in vivo.
Expression of H-RASV12 in a zebrafish model of Costello syndrome causes cellular senescence in adult proliferating cells
Authors: Santoriello Cristina , Deflorian Gianluca , Pezzimenti Federica , Kawakami Koichi , Lanfrancone Luisa , d’Adda di Fagagna Fabrizio , Mione Marina
Published: December 2008

Constitutively active, ‘oncogenic’ H-RAS can drive proliferation and transformation in human cancer, or be a potent inducer of cellular senescence. Moreover, aberrant activation of the Ras pathway owing to germline mutations can cause severe developmental disorders. In this study we have generated transgenic zebrafish that constitutively express low levels, or can be induced to express high levels, of oncogenic H-RAS. We observed that fish carrying the integrated transgene in their germline display several hallmarks of Costello syndrome, a rare genetic disease caused by activating mutations in the gene H-RAS, and can be used as a model for the disease. In Costello-like fish, low levels of oncogenic H-RAS expression are associated with both reduced proliferation and an increase in senescence markers in adult progenitor cell compartments in the brain and heart, together with activated DNA damage responses. Overexpression of H-RAS through a heat-shock-inducible promoter in larvae led to hyperproliferation, activation of the DNA damage response and tp53-dependent cell cycle arrest. Thus, oncogene-induced senescence of adult proliferating cells contributes to the development of Costello syndrome and provides an alternative pathway to transformation in the presence of widespread constitutively active H-RAS expression.
A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle
Authors: Dutton Kirsten , Abbas Leila , Spencer Joanne , Brannon Claire , Mowbray Catriona , Nikaido Masataka , Kelsh Robert N. , Whitfield Tanya T.
Published: December 2008

In humans, mutations in the SOX10 gene are a cause of the auditory-pigmentary disorder Waardenburg syndrome type IV (WS4) and related variants. SOX10 encodes an Sry-related HMG box protein essential for the development of the neural crest; deafness in WS4 and other Waardenburg syndromes is usually attributed to loss of neural-crest-derived melanocytes in the stria vascularis of the cochlea. However, SOX10 is strongly expressed in the developing otic vesicle and so direct roles for SOX10 in the otic epithelium might also be important. Here, we examine the otic phenotype of zebrafish sox10 mutants, a model for WS4. As a cochlea is not present in the fish ear, the severe otic phenotype in these mutants cannot be attributed to effects on this tissue. In zebrafish sox10 mutants, we see abnormalities in all otic placodal derivatives. Gene expression studies indicate deregulated expression of several otic genes, including fgf8, in sox10 mutants. Using a combination of mutant and morphant data, we show that the three sox genes belonging to group E (sox9a, sox9b and sox10) provide a link between otic induction pathways and subsequent otic patterning: they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions. Single-cell labelling experiments indicate a small and transient neural crest contribution to the zebrafish ear during normal development, but this is unlikely to account for the strong defects seen in the sox10 mutant. We discuss the implication that the deafness in WS4 patients with SOX10 mutations might reflect a haploinsufficiency for SOX10 in the otic epithelium, resulting in patterning and functional abnormalities in the inner ear.
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.
Consensus recommendations for cervical cancer prevention in the Czech Republic: a report of the International Conference on Human Papillomavirus in Human Pathology (Prague, 1–3 May 2008)
Authors: Tachezy Ruth , Davies Philip , Arbyn Marc , Rob Lukás , Lazdane Gunta , Petrenko Jana , Hamsíková Eva , Beková Alena , Klozar Jan , Dusková Jaroslava
Published: December 2008

A comparison of cervical cancer incidence and mortality in the Czech Republic with that from other countries shows that the burden of cervical cancer here is considerably higher than in Western Europe, where screening is widespread. In May 2008, the International Conference on Human Papillomavirus in Human Pathology was convened to review the latest evidence and to formulate consensus recommendations for the reduction of cervical cancer rates. The Czech Republic is spending considerable resources on cervical cancer prevention, but these resources are being used inefficiently. The current system is characterized by a lack of coordination and monitoring that leads to the over-screening of a minority of women while the majority of the target population are under-screened or not screened at all. It was recommended that a comprehensive, organized programme be implemented, coordinated by an independent administrative body with legal and budgetary responsibility. As the laboratory infrastructure and professional technical skills required for a quality-assured organized screening programme are already in place, implementation of this programme would not require much in the way of additional resources to produce substantial cost-effective reductions in cervical cancer rates.
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.
Emissions Compliance in the Fossil-Fuel Based Energy Sector
Authors: Bill Alain , Bitran Guillaume , Basler Benno , Hess Stephan
Published: December 2008

Most of today's air pollution legislation varies from country to country depending on factors such as the economy, fuel supply, fuel dependency and specific local pollution problems. At the same time, in a growing number of countries, the energy sector is going through a privatisation, deregulation and globalisation process which is affecting energy demand and fuel selection, driving gradual integration of energy markets and requiring new solutions. It is now also well recognized that pollution is often not a localized problem and that gaseous air pollutants can cross great distances. This has led to the cooperation between countries to control transboundary pollution, under bilateral or multilateral agreements. As for the energy sector, countries are not only becoming increasingly linked in political, economic and social terms but also in environmental terms. Power generators and equipment manufacturers have been developing technologies and business agreements in countries with respective legislation constraints over many years and take this trend of interdependence into account. The equipment manufacturers and global solution providers such as Alstom have become the focal point driving the development of new environmental compliance products and solutions within the fossil fuel based energy sector to meet these increasingly stringent emissions reduction requirements while extending the plant lifetime of existing power plants, and keeping them competitive. This paper gives an overview and outlook of environmental regulations, air pollution control technologies and some experience in pioneering environmental long-term service agreements. The most immediately effective way to ensure emissions compliance of existing power plant is obviously to professionally maintain and upgrade the plant in order to guarantee high availability and operating reliability. The second option is to take advantage of monitoring and control systems for continuous process supervision and optimisation. Regular monitoring and fine-tuning of the plant by an expert team using state of the art technology indeed guarantees the lowest possible emissions and energy consumption. A long-term service partnership can secure, for the power generator, plant availability and full environmental compliance.
The Competition for Oil and Gas in Africa
Authors: Xu Yi-Chong
Published: December 2008

China and the US are two key players in the recent round of ‘scrambling’ for Africa. They compete for control over oil and other strategic resources, for markets, and for political influence. To understand the concerns of many who have been alarmed by the competition, this article identifies what the US and China are actually doing in Africa and explains how they perceive each other's activities. It argues that alarmists often consider the ambitions of both China and the US in isolation; when laid out side by side, the extent to which their activities in Africa overlap or clash can be seen more clearly. That is, China and the US are seeking different things at different places in the continent and are careful not to step on the each other's toe. Their activities do not support the dire prediction. The ‘scramble for Africa’ may irritate; it is unlikely to cause direct confrontations because competition remains by and large economic and economic competition in an integrated global market creates networks of constraints that ameliorate potential confrontation.
Hydrocarbons Reserves in Venezuela
Authors: Cruz Diego J. González
Published: December 2008

Venezuela is an important player in the energy world because of its hydrocarbons reserves. The process for calculating oil and associated gas reserves is described bearing in mind that 90% of the gas reserves of Venezuela are associated to oil. An analysis is presented of oil reserves figures 1975–2003. Reference is made to inconsistencies in these data found by international experts and including changes that took place in the 1980s, and the explanations offered for these by the Ministry of Energy and Petroleum (MENPET) and Petróleos de Venezuela (PDVSA). The reserves of associated gas are analysed as related to the different crude oils and the use of gas injection. Possible changes for gas are discussed if the figures for oil reserves were revised. Hubbert's Law is explained as a tool for determining peak production of conventional oil. The interest of the United Nations in this issue is emphasised. Some recommendations are submitted so that the MENPET may start to prepare the pertinent policies governing reserves.
Hungary-Ukraine Energy Cooperation and Its Contribution to the Security of Supply in the European Union
Authors: Kiss Péter
Published: December 2008

The European Union (EU) is expected to be increasingly dependent upon non-EU primary energy resources as domestic resources are depleted. Ukraine is the largest country in the world by the volume of gas transit: Annually through the Ukrainian gas pipeline the transit gas deliveries amount to 140 billion m3 including 120 billion m3 to countries of Central and Western Europe. Ukraine also has an underutilized 750 kV transmission line that reaches into the heart of the neighbouring EU member Hungary. This high-level natural gas transportation infrastructure and the existence of major electricity transmission lines results in Eastern Hungary being a key location for a 2,400MW Combined Cycle Gas Turbine (CCGT) plant. A large CCGT power plant usinig the best available technology in this region would not only benefit from existing infrastructure but also provide electricity for the Central and Eastern European (CEE) region, and may supply the impetus for major regional development initiatives.(1)
Energy Security and Evolution of Gas Markets
Authors: Mitrova Tatiana
Published: December 2008

Questions of energy security and international gas trade have recently become indissolubly connected. Paradoxically, during the evolution of natural gas markets, concerns about security issues in gas trade were growing at the same time as transaction costs. Market participants have developed several mechanisms of adaptation (vertical integration, mutual penetration of capital and long-term contracts) which should be regarded not as a market failure, but as an essential part of current energy security guarantees. Further gas market evolution will demand a more unified institutional framework to reduce both threats to energy security and transaction costs. This framework should be a result of mutual compromise between all market participants.
The Absorption Characteristics of Muslim Worshippers
Authors: Oldham D. J. , Elkhateeb A.
Published: December 2008

The Masjid (Mosque) is the most important architectural space in the religious life of the Muslim. However, although considerable effort has been spent on the investigation of the absorption coefficient of an audience in many other situations, the absorption characteristics of people performing prayers according to the Islamic rules have never been measured. As this information is essential for the design of the acoustics of Masjids, this work describes an investigation of the absorption per person, Aobj, for the worshippers performing prayer according to Islamic rules. The absorption characteristics of Muslim worshippers have been investigated in the reverberation chamber of the Acoustic Research Unit, University of Liverpool according to BS- EN-ISO 354:2003. The four positions of the group prayer according to the Islamic rules (standing, bowing, prostration and sitting in rows on carpet) were simulated with thirteen male persons in the reverberation chamber in addition to a fifth position where the audience were sitting down in a random way on carpet to simulate the position of listening to the Friday sermon. Results were calculated for the sound absorption per person and compared with other reported values of audience absorption. Results showed that at the mid and high frequencies the maximum absorption occurs for the standing position followed by the bowing position, the random sitting position, the sitting in rows position and finally the prostrate position which exhibited the minimum values.