bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving uptake in non-attenders of breast screening: selective use of second appointment
Authors: Stead M J , Wallis M G , Wheaton M E 
Published: May 2013

Objective To find the most cost and time effective way of increasing uptake by reinvitation of non-attenders after an initial invitation. Setting Women from the Warwickshire, Solihull, and Coventry breast screening programme who failed to attend their initial invitation. Method Between October 1996 and February 1997, 2229 women who had failed to attend and had not declined their first invitation to screening were split into two groups according to their Sx number (a number allocated to all women when they are called for screening). Women with an odd number received a “open” invitation asking them to telephone the screening unit for another appointment and women with an even number were given a second “fixed” appointment time. The response of both groups of women was monitored. Results There was a significant difference (p<0.001) in response to a second invitation between the open invitation and fixed appointment letter (12.3% v 22.8%). The greatest disparities were between those who had attended screening in both preceding rounds and those who had failed to attend either round. Socioeconomic status measured by Townsend scores did not seem to affect the response to second appointments. Conclusion Second appointments are an important way of increasing screening uptake and thus reducing mortality, which should not be dismissed. The type of invitation is important, with fixed appointments being more effective, and the best predictor of attendance being attendance in the previous screening rounds. This information can be used to allocate resources efficiently to achieve an increased uptake. Recommendations All women should receive a second invitation, ideally as a timed appointment. However, if this appointment strategy prevents an individual screening programme maintaining a three year cycle, we have identified a group of women for whom a simple reminder letter would maintain increased uptake while allowing savings in appointment scheduling.
Investigation of the effect of occult invasive cancer on progress towards successful cervical screening
Authors: Herbert A , Bryant T N , Campbell M J , Smith J 
Published: May 2013

Objectives To describe the effect of occult invasive disease on progress towards meeting the Health of the Nation target for reducing the incidence of cervical cancer, and to investigate the possible effect of a higher risk of cervical cancer in women born since 1940. Setting Southampton and South West Hampshire (SSWH), with a total female population of 218 549 in 1990, the midpoint of a study period covering 1985 to 1995. Methods Incidence was calculated per 100 000 women years at risk in overlapping three year periods for symptomatic and screen detected cancers. The same method was used for cohorts of women born before and after 1940. Screen detected stage Ia1 cancers were identified as a subgroup. Results The incidence of invasive cervical cancer fell by 27.4%, from 16.8 to 12.2 per 100 000 women years at risk between 1985–87 and 1993–95, which was a significant linear trend (χ2=4.494, df=1, p=0.034). The corresponding figures adjusted for age in a standardised European population were 16.3 and 11.5: a fall greater than required to meet the Health of the Nation target set for the year 2000. Incidence remained relatively high until screen detected cancers, more than one third of which were stage Ia1, had passed a peak in 1992. When screen detected stage Ia1 cancers were excluded, incidence fell by 41.2%, from 16.5 to 9.7 per 100 000 women years at risk: a highly significant linear trend (χ2=12.391, df=1, p<0.001). The incidence in the first three years of the study was higher in women born between 1940 and 1954 than in those born between 1925 and 1939, though the reverse would be expected by age and the natural history of the disease. In the 1940–54 birth cohort 44% (23/52) of screen detected cancers were stage Ia1, with a peak in 1992. When these were excluded, incidence fell by 57.1%, from 31.7 to 13.6 per 100 000 women years at risk: a highly significant linear trend (χ2=13.704, df=1, p<0.001), whereas an increase would be expected for a cohort aged from 30–45 to 40–55. In the 1925–39 cohort only 24% (8/33) of screen detected cancers were stage Ia1. When these were excluded, incidence fell by 35.3%, from 24.9 to 16.1, which was not a significant linear trend (χ2=0.409, df=1, p=0.522). Conclusion An overall decline in incidence was not achieved until prevalent occult invasive disease had been detected by improved screening. The data confirm the effectiveness of screening, particularly in a high risk cohort of women born between 1940 and 1954.
Obstacles to timely neonatal screening in North Thames
Authors: Ades A E , Walker J , Jones R , Thompson S , Leonard J V , Smith I 
Published: May 2013

Objective To assess the timeliness of neonatal (Guthrie card) screening in North Thames, and to identify the most effective ways of improving it. Design Analysis of information routinely collected in the course of neonatal screening; reanalysis of published data on blood phenylalanine concentration in phenylketonuria (PKU) over the first two weeks; simulation studies on the impact of different interventions. Subjects 100 690 infants born over one year and screened at Great Ormond Street Hospital NHS Trust. Outcome measureInterval between birth and reading PKU screen results. Results Although 75% of samples (district range 55–91%) were collected by day 7, only 81% had arrived in the laboratory seven days later (range 57–96%). The average interval between birth and reading results was 14.5 days, with only 9.7% read by day 10. Samples could be collected from day 4 without significant impact on false negative rates for PKU. If samples were collected from day 4 and posted promptly (second class), the average interval between birth and reading results could be reduced to 9.3 days. If first class mail were used and the laboratory operated on Saturdays, and used assays that could be read the same day rather than bacterial inhibition assays, the average would be 7.8 days, with 96% read by day 10. Conclusion Timeliness of neonatal screening shows unacceptable variation between districts, and delays in dispatch of specimens to the laboratory. Same day, first class posting should be introduced, and samples could be collected between days 4 and 8.
Methodological issues in mammography double reading studies
Authors: Williams L J , Hartswood M , Prescott R J 
Published: May 2013

Objectives An examination of the methods used in assessing cancer detection rates in double reading studies to obtain a clear interpretation of the disparate results from differing studies. Setting National breast screening programmes. Methods Critical appraisal of methodologies used in the comparison of cancer detection rates with single or double reading. Results The reported improvement in cancer detection rate with double reading varies greatly between studies, depending upon whether the study is blinded and the statistic used. A method of calculating the increase in cancer detection rate due to a second reader is proposed.
Reduction in breast cancer mortality due to the introduction of mass screening in the Netherlands: comparison with the United Kingdom
Authors: van den Akker-van Marle E. , de Koning H. , Boer R. , van der Maas P. 
Published: May 2013

Objective To assess the impact of the national breast cancer screening programme on breast cancer mortality in the first years after its introduction. Setting The Netherlands and United Kingdom. Methods —MISCAN models, incorporating demographic, epidemiological, and screening characteristics of the region under study, were used to assess the mortality in the presence and absence of screening. Results Breast cancer mortality decreased in women aged 55–74 as the Dutch nationwide screening programme built up, and was 5% lower in 1996 than before the start of the programme. The mortality reduction due to screening in the age group 55–74 is expected to increase gradually to 18% in 1999, 10 years after the introduction of screening, and to 29% in the long term. In the United Kingdom screening was expected to achieve a mortality reduction of 5% and 18% in the age group 55–69 five and 10 years respectively after screening was started. A maximum mortality reduction of 24% in this age group is predicted. Conclusions —The effects of screening will be small in the first years after the start of the programme. Accordingly, it was expected that the reduction in breast cancer mortality due to the Dutch nationwide breast screening programme, which started around 1989, would be statistically significant from 1997 onwards, the point at which the target population of women was completely covered; 70% of the reported 12% mortality reduction in England and Wales in 1994 is expected to be attributed to screening.
Stage distribution at first and repeat examinations in breast cancer screening
Authors: Boer R. , de Koning H. , van Oortmarssen G. , Warmerdam P. , van der Maas P. 
Published: May 2013

Objectives To investigate observed stage distributions at first and repeat screenings. To compare the observed outcomes with expected values based on simulation modelling, varying the assumptions about the natural history of the disease. Methods An overview is made of observed data on stage distribution at first and repeat screenings and the difference between those distributions is summarised in a Gini coefficient. Four possible explanations for the observations are considered, two of these are worked out as Miscan simulation models, and the outcomes are compared with observations. Results Often the reported stage distributions at repeat screenings are not or only slightly more favourable than at first screenings and, in the ones that are more favourable, the difference is relatively small. If, in the Miscan model, it is assumed that there is no correlation between the duration of preclinical breast cancer in consecutive tumour size categories and that there is a strong influence of latent cancers, it is not possible to reproduce the observed outcomes. Conclusions The two modelled explanations are not sufficient. Decreasing sensitivity seems an unlikely explanation for the discrepancy in many screening programmes. The possibility that the observations may be explained because false reassurance has been given should be seriously considered and investigated.
CX3CL1 Promotes Breast Cancer via Transactivation of the EGF Pathway
Authors: Tardáguila Manuel , Mira Emilia , García-Cabezas Miguel A. , Feijoo Anna M. , Quintela-Fandino Miguel , Azcoitia Iñigo , Lira Sergio A. , Mañes Santos 
Published: May 2013

Abstract
Chemokines are relevant molecules in shaping the tumor microenvironment, although their contributions to tumorigenesis are not fully understood. We studied the influence of the chemokine CX3CL1/fractalkine in de novo breast cancer formation using HER2/neu transgenic mice. CX3CL1 expression was downmodulated in HER2/neu tumors, yet, paradoxically, adenovirus-mediated CX3CL1 expression in the tumor milieu enhanced mammary tumor numbers in a dose-dependent manner. Increased tumor multiplicity was not a consequence of CX3CL1-induced metastatic dissemination of the primary tumor, although CX3CL1 induced epithelial-to-mesenchymal transition in breast cancer cells in vitro. Instead, CX3CL1 triggered cell proliferation by induction of ErbB receptors through the proteolytic shedding of an ErbB ligand. This effect was important insofar as mammary tumorigenesis was delayed and tumor multiplicity was reduced by genetic deletion of CX3CL1 in HER2/neu mice, but not in polyoma middle T-antigen oncomice. Our findings support the conclusion that CX3CL1 acts as a positive modifier of breast cancer in concert with ErbB receptors. Cancer Res; 73(14); 4461–73. ©2013 AACR.
Climate Change Effects on Hydropower Potential in the Alcantara River Basin in Sicily (Italy)
Authors: Aronica G. T. , Bonaccorso B. 
Published: May 2013

Abstract
In recent years, increasing attention has been paid to hydropower generation, since it is a renewable, efficient, and reliable source of energy, as well as an effective tool to reduce the atmospheric concentrations of greenhouse gases resulting from human activities. At the same time, however, hydropower is among the most vulnerable industries to global warming, because water resources are closely linked to climate changes. Indeed, the effects of climate change on water availability are expected to affect hydropower generation with special reference to southern countries, which are supposed to face dryer conditions in the next decades. The aim of this paper is to qualitatively assess the impact of future climate change on the hydrological regime of the Alcantara River basin, eastern Sicily (Italy), based on Monte Carlo simulations. Synthetic series of daily rainfall and temperature are generated, based on observed data, through a first-order Markov chain and an autoregressive moving average (ARMA) model, respectively, for the current scenario and two future scenarios at 2025. In particular, relative changes in the monthly mean and standard deviation values of daily rainfall and temperature at 2025, predicted by the Hadley Centre Coupled Model, version 3 (HadCM3) for A2 and B2 greenhouse gas emissions scenarios, are adopted to generate future values of precipitation and temperature. Synthetic series for the two climatic scenarios are then introduced as input into the Identification of Unit Hydrographs and Component Flows from Rainfall, Evapotranspiration and Streamflow Data (IHACRES) model to simulate the hydrological response of the basin. The effects of climate change are investigated by analyzing potential modification of the resulting flow duration curves and utilization curves, which allow a site's energy potential for the design of run-of-river hydropower plants to be estimated.
Homogeneity of the Subgrid-Scale Turbulent Mixing in Large-Eddy Simulation of Shallow Convection
Authors: Jarecka Dorota , Grabowski Wojciech W. , Morrison Hugh , Pawlowska Hanna 
Published: May 2013

Abstract
This paper presents an approach to locally predict homogeneity of the subgrid-scale turbulent mixing in large-eddy simulation of shallow clouds applying double-moment warm-rain microphysics. The homogeneity of subgrid-scale mixing refers to the partitioning of the cloud water evaporation due to parameterized entrainment between changes of the mean droplet radius and changes of the mean droplet concentration. Homogeneous and extremely inhomogeneous mixing represent two limits of possible scenarios, where the droplet concentration and the mean droplet radius remains unchanged during the microphysical adjustment, respectively. To predict the subgrid-scale mixing scenario, the double-moment microphysics scheme is merged with the approach to delay droplet evaporation resulting from entrainment. Details of the new scheme and its application in the Barbados Oceanographic and Meteorological Experiment (BOMEX) shallow convection case are discussed. The simulated homogeneity of mixing varies significantly inside small convective clouds, from close to homogeneous to close to extremely inhomogeneous. The mean mixing characteristics become more homogeneous with height, reflecting increases of the mean droplet size and the mean turbulence intensity, both favoring homogeneous mixing. Model results are consistent with microphysical effects of entrainment and mixing deduced from field observations. Mixing close to homogeneous is predicted in volumes with the highest liquid water content (LWC) and strongest updraft at a given height, whereas mixing in strongly diluted volumes is typically close to extremely inhomogeneous. The simulated homogeneity of mixing has a small impact on mean microphysical characteristics. This result agrees with the previous study applying prescribed mixing scenarios and can be explained by the high humidity of the clear air involved in the subgrid-scale mixing.
Ensemble Representation of Uncertainty in Lagrangian Satellite Rainfall Estimates
Authors: Bellerby T. J. 
Published: May 2013

Abstract
A new algorithm called Lagrangian Simulation (LSIM) has been developed that enables the interpolation uncertainty present in Lagrangian satellite rainfall algorithms such as the Climate Prediction Center (CPC) morphing technique (CMORPH) to be characterized using an ensemble product. The new algorithm generates ensemble sequences of rainfall fields conditioned on multiplatform multisensor microwave satellite data, demonstrating a conditional simulation approach that overcomes the problem of discontinuous uncertainty fields inherent in this type of product. Each ensemble member is consistent with the information present in the satellite data, while variation between members is indicative of uncertainty in the rainfall retrievals. LSIM is based on the combination of a Markov weather generator, conditioned on both previous and subsequent microwave measurements, and a global optimization procedure that uses simulated annealing to constrain the generated rainfall fields to display appropriate spatial structures. The new algorithm has been validated over a region of the continental United States and has been shown to provide reliable estimates of both point uncertainty distributions and wider spatiotemporal structures.
Epithelial cytoprotection sustains ectopic expression of tissue-restricted antigens in the thymus during murine acute GVHD
Authors: Dertschnig Simone , Nusspaumer Gretel , Ivanek Robert , Hauri-Hohl Mathias M. , Holländer Georg A. , Krenger Werner 
Published: May 2013

Key PointsAcute GVHD predisposes to autoimmune chronic GVHD, but it is currently unclear how autoimmunity is linked to antecedent alloimmunity. Loss of central tolerance induction that occurs via functional compromise of thymic epithelial cells may provide such a pathogenic link.
The Rac activator DOCK2 regulates natural killer cell–mediated cytotoxicity in mice through the lytic synapse formation
Authors: Sakai Yusuke , Tanaka Yoshihiko , Yanagihara Toyoshi , Watanabe Mayuki , Duan Xuefeng , Terasawa Masao , Nishikimi Akihiko , Sanematsu Fumiyuki , Fukui Yoshinori 
Published: May 2013

Key PointsDOCK2-deficienct NK cells fail to effectively kill leukemia cells in vitro and major histocompatibility complex class I–deficient bone marrow cells in vivo. Activating NK receptor–mediated Rac activation and the lytic synapse formation are severely impaired in DOCK2-deficient NK cells.
The venus kinase receptor (VKR) family: structure and evolution
Authors: Vanderstraete Mathieu , Gouignard Nadège , Ahier Arnaud , Morel Marion , Vicogne Jérôme , Dissous Colette 
Published: May 2013

Abstract

Background
Receptor tyrosine kinases (RTK) form a family of transmembrane proteins widely conserved in Metazoa, with key functions in cell-to-cell communication and control of multiple cellular processes. A new family of RTK named Venus Kinase Receptor (VKR) has been described in invertebrates. The VKR receptor possesses a Venus Fly Trap (VFT) extracellular module, a bilobate structure that binds small ligands to induce receptor kinase activity. VKR was shown to be highly expressed in the larval stages and gonads of several invertebrates, suggesting that it could have functions in development and/or reproduction.

Results
Analysis of recent genomic data has allowed us to extend the presence of VKR to five bilaterian phyla (Platyhelminthes, Arthropoda, Annelida, Mollusca, Echinodermata) as well as to the Cnidaria phylum. The presence of NveVKR in the early-branching metazoan Nematostella vectensis suggested that VKR arose before the bilaterian radiation. Phylogenetic and gene structure analyses showed that the 40 receptors identified in 36 animal species grouped monophyletically, and likely evolved from a common ancestor. Multiple alignments of tyrosine kinase (TK) and VFT domains indicated their important level of conservation in all VKRs identified up to date. We showed that VKRs had inducible activity upon binding of extracellular amino-acids and molecular modeling of the VFT domain confirmed the structure of the conserved amino-acid binding site.

Conclusions
This study highlights the presence of VKR in a large number of invertebrates, including primitive metazoans like cnidarians, but also its absence from nematodes and chordates. This little-known RTK family deserves to be further explored in order to determine its evolutionary origin, its possible interest for the emergence and specialization of Metazoa, and to understand its function in invertebrate development and/or reproductive biology.
A large-scale assessment of hand hygiene quality and the effectiveness of the “WHO 6-steps”
Authors: Szilágyi László , Haidegger Tamás , Lehotsky Ákos , Nagy Melinda , Csonka Erik-Artur , Sun Xiuying , Ooi Kooi Li , Fisher Dale 
Published: May 2013

Abstract

Background
Hand hygiene compliance is generally assessed by observation of adherence to the “WHO five moments” using numbers of opportunities as the denominator. The quality of the activity is usually not monitored since there is no established methodology for the routine assessment of hand hygiene technique. The aim of this study was to objectively assess hand rub coverage of staff using a novel imaging technology and to look for patterns and trends in missed areas after the use of WHO’s 6 Step technique.

Methods
A hand hygiene education and assessment program targeted 5200 clinical staff over 7 days at the National University Hospital, Singapore. Participants in small groups were guided by professional trainers through 5 educational stations, which included technique-training and UV light assessment supported by digital photography of hands. Objective criteria for satisfactory hand hygiene quality were defined a priori. The database of images created during the assessment program was analyzed subsequently. Patterns of poor hand hygiene quality were identified and linked to staff demographic.

Results
Despite the assessment taking place immediately after the training, only 72% of staff achieved satisfactory coverage. Failure to adequately clean the dorsal and palmar aspects of the hand occurred in 24% and 18% of the instances, respectively. Fingertips were missed by 3.5% of subjects. The analysis based on 4642 records showed that nurses performed best (77% pass), and women performed better than men (75% vs. 62%, p<0.001). Further risk indicators have been identified regarding age and occupation.

Conclusion
Ongoing education and training has a vital role in improving hand hygiene compliance and technique of clinical staff. Identification of typical sites of failure can help to develop improved training.