Increased cancer risk in patients undergoing dialysis: a population-based cohort study in North-Eastern Italy

open116noBACKGROUND: In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. METHODS: A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998-2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15-1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42-2.45 for age 40-59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89-10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06-4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46-2.22), oral cavity (SIR = 2.42, 95% CI: 1.36-4.00), and Kaposi's sarcoma (SIR = 10.29, 95% CI: 1.25-37.16). CONCLUSIONS: The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.openTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Sarah Shalaby, Raffaella Petrara, Patrizia Burra, Giacomo Zanus, Stefano Zanini,Paolo Rigotti; Maria Rendina, AlfredoDi Leo, Francesco Paolo Schena, Giuseppe Grandaliano, Marco Fiorentino, Augusto Lauro, Antonio Daniele Pinna, PaoloDi Gioia, Sara Pellegrini, Chiara Zanfi, Maria Piera Scolari, Sergio Stefoni, PaolaTodeschini, Laura Panicali, Chiara Valentini, Umberto Baccarani, Andrea Risaliti, Gian Luigi Adani, Dario Lorenzin, Giuseppe Maria Ettorre, Giovanni Vennarecci,Marco Colasanti, Manuela Coco, Fabrizio Ettorre, Roberto Santoro, LuciaMiglioresi, Francesco Nudo, Massimo Rossi,Gianluca Mennini, Luca Toti, GiuseppeTisone, Annachiara Casella, Laura Fazzolari, Daniele Sforza, Giuseppe Iaria,Carlo Gazia, Chiara Belardi, ClaudiaCimaglia, Alessandro Agresta, Gianpiero D’Offizi, Ubaldo Visco Comandini,Raffaella Lionetti, Marzia Montalbano, Chiara Taibi, Giovanni Fantola, Fausto Zamboni, Gian Benedetto Piredda,Maria Benigna Michittu, Maria Gavina Murgia, Bruno Onano, Lucia Fratino, Luigino Dal Maso, Paolo De Paoli, Diana Verdirosi,Emanuela Vaccher, Francesco Pisani, Antonio Famulari, Federica Delreno, Samuele Iesari, LindaDe Luca, Maurizio Iaria, Enzo Capocasale,Elena Cremaschi, Silvio Sandrini, Francesca Valerio,Valentina Mazzucotelli, Nicola Bossini, Gisella Setti, Massimiliano Veroux, Pierfrancesco Veroux, Giuseppe Giuffrida,Alessia Giaquinta, Domenico Zerbo, GhilBusnach, Laura Di Leo, Maria Luisa Perrino, Marialuisa Querques, ValerianaColombo, Maria Chiara Sghirlanzoni , Piergiorgio Messa, Antonio Leoni , Laura Galatioto, Salvatore Gruttadauria, Vito Sparacino, FlaviaCaputo, Barbara Buscemi ,Franco Cit-terio, Gionata Spagnoletti, Maria Paola Salerno, Evaldo Favi Giuseppe Paolo Segoloni, Luigi Biancone, AntonioLavacca, Maria Cristina Maresca, CarmeloCascone, Bice Virgilio, Donato Donati, Fiorella Dossi, Andrea Fontanella, Andrea Ambrosini, Marco Di CiccoTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Shalaby, Sarah; Petrara, MARIA RAFFAELLA; Burra, Patrizia; Zanus, Giacomo; Zanini, Stefano; Rigotti, Paolo; Maria, Rendina; Alfredodi, Leo; Francesco Paolo Schena, ; Giuseppe, Grandaliano; Marco, Fiorentino; Augusto, Lauro; Antonio Daniele Pinna, ; Paolodi, Gioia; Sara, Pellegrini; Chiara, Zanfi; Maria Piera Scolari, ; Sergio, Stefoni; Paolatodeschini, ; Laura, Panicali; Chiara, Valentini; Umberto, Baccarani; Andrea, Risaliti; Gian Luigi Adani, ; Dario, Lorenzin; Giuseppe Maria Ettorre, ; Giovanni, Vennarecci; Marco, Colasanti; Manuela, Coco; Fabrizio, Ettorre; Roberto, Santoro; Luciamiglioresi, ; Francesco, Nudo; Massimo, Rossi; Gianluca, Mennini; Luca, Toti; Giuseppetisone, ; Annachiara, Casella; Laura, Fazzolari; Daniele, Sforza; Giuseppe, Iaria; Carlo, Gazia; Chiara, Belardi; Claudiacimaglia, ; Alessandro, Agresta; Gianpiero, D’Offizi; Ubaldo Visco Comandini, ; Raffaella, Lionetti; Marzia, Montalbano; Chiara, Taibi; Giovanni, Fantola; Fausto, Zamboni; Gian Benedetto Piredda, ; Maria Benigna Michittu, ; Maria Gavina Murgia, ; Bruno, Onano; Lucia, Fratino; Luigino Dal Maso, ; Paolo De Paoli, ; Diana, Verdirosi; Emanuela, Vaccher; Francesco, Pisani; Antonio, Famulari; Federica, Delreno; Samuele, Iesari; Lindade, Luca; Maurizio, Iaria; Enzo, Capocasale; Elena, Cremaschi; Silvio, Sandrini; Francesca, Valerio; Valentina, Mazzucotelli; Nicola, Bossini; Gisella, Setti; Massimiliano, Veroux; Pierfrancesco, Veroux; Giuseppe, Giuffrida; Alessia, Giaquinta; Domenico, Zerbo; Ghilbusnach, ; Laura Di Leo, ; Maria Luisa Perrino, ; Marialuisa, Querques; Valerianacolombo, ; Maria Chiara Sghirlanzoni, ; Piergiorgio, Messa; Antonio, Leoni; Laura, Galatioto; Salvatore, Gruttadauria; Vito, Sparacino; Flaviacaputo, ; Barbara, Buscemi; Franco, Cit-terio; Gionata, Spagnoletti; Maria Paola Salerno, ; Evaldo Favi Giuseppe Paolo Segoloni, ; Luigi, Biancone; Antoniolavacca, ; Maria Cristina Maresca, ; Carmelocascone, ; Bice, Virgilio; Donato, Donati; Fiorella, Dossi; Andrea, Fontanella; Andrea, Ambrosini; Marco Di Cicco

Accuracy of intracranial pressure monitoring : systematic review and meta-analysis

Introduction: Intracranial pressure (ICP) measurement is used to tailor interventions and to assist in formulating the prognosis for traumatic brain injury patients. Accurate data are therefore essential. The aim of this study was to verify the accuracy of ICP monitoring systems on the basis of a literature review. Methods: A PubMed search was conducted from 1982 to 2014, plus additional references from the selected papers. Accuracy was defined as the degree of correspondence between the pressure read by the catheter and a reference "real" ICP measurement. Studies comparing simultaneous readings from at least two catheters were included. Drift was defined as the loss of accuracy over the monitoring period. Meta-analyses of data from the studies were used to estimate the overall mean difference between simultaneous ICP measurements and their variability. Individual studies were weighted using both a fixed and a random effects model. Results: Of 163 articles screened, 83 compared two intracranial catheters: 64 reported accuracy and 37 drift(some reported both). Of these, 10 and 17, respectively, fulfilled the inclusion criteria for accuracy and zero drift analysis. The combined mean differences between probes were 1.5mmHg (95% confidence interval (CI) 0.7-2.3) with the random effects model and 1.6mmHg (95% CI 1.3-1.9) with the fixed effects model. The reported mean drift over a long observation period was 0.75mmHg. No relation was found with the duration of monitoring or differences between various probes. Conclusions: This study confirms that the average error between ICP measures is clinically negligible. The random effects model, however, indicates that a high percentage of readings may vary over a wide range, with clinical implications both for future comparison studies and for daily care

Label-free monitoring of tissue biochemistry following traumatic brain injury using Raman spectroscopy.

Traumatic brain injury (TBI) constitutes a major cause of death and long-term disability. At present, we lack methods to non-invasively track tissue biochemistry and hence select appropriate interventions for patients. We hypothesized that detailed label-free vibrational chemical analysis of focal TBI could provide such information. We assessed the early spatial and temporal changes in tissue biochemistry that are associated with brain injury in mice. Numerous differences were observed in the spectra of the contusion core and pericontusional tissue between 2 and 7 days. For example, a strong signal from haem was seen in the contusion core at 2 days due to haemorrhage, which subsequently resolved. More importantly, elevated cholesterol levels were demonstrated by 7 days, which may be a marker of important cell repair processes. Principal component analysis revealed an early 'acute' component dominated by haemorrhage and a delayed component reflecting changes in protein and lipid composition. Notably we demonstrated changes in Raman signature with time even in the contralateral hemisphere when compared to sham control mice. Raman spectroscopy therefore shows promise as a probe that is sensitive to important pathobiological processes in TBI and could be applied in future both in the experimental setting, as well as in the clinic

Intracranial pressure after subarachnoid hemorrhage

Objectives: To describe mean intracranial pressure after aneurysmal subarachnoid hemorrhage, to identify clinical factors associated with increased mean intracranial pressure, and to explore the relationship between mean intracranial pressure and outcome. Design: Analysis of a prospectively collected observational database. Setting: Neuroscience ICU of an academic hospital. Patients: One hundred sixteen patients with subarachnoid hemorrhage and intracranial pressure monitoring. Interventions: None. Measurements and Main Results: Episodes of intracranial pressure greater than 20 mm Hg lasting at least 5 minutes and the mean intracranial pressure for every 12-hour interval were analyzed. The highest mean intracranial pressure was analyzed in relation to demographic characteristics, acute neurologic status, initial radiological findings, aneurysm treatment, clinical vasospasm, and ischemic lesion. Mortality and 6-month outcome (evaluated using a dichotomized Glasgow Outcome Scale) were also introduced in multivariable logistic models. Eighty-one percent of patients had at least one episode of high intracranial pressure and 36% had a highest mean intracranial pressure more than 20 mm Hg. The number of patients with high intracranial pressure peaked 3 days after subarachnoid hemorrhage and declined after day 7. Highest mean intracranial pressure greater than 20 mm Hg was significantly associated with initial neurologic status, aneurysmal rebleeding, amount of blood on CT scan, and ischemic lesion within 72 hours from subarachnoid hemorrhage. Patients with highest mean intracranial pressure greater than 20 mm Hg had significantly higher mortality. When death, vegetative state, and severe disability at 6 months were pooled, however, intracranial pressure was not an independent predictor of unfavorable outcome. Conclusions: High intracranial pressure is a common complication in the first week after subarachnoid hemorrhage in severe cases admitted to ICU. Mean intracranial pressure is associated with the severity of early brain injury and with mortality

Brain oxygen tension, oxygen supply, and oxygen consumption during arterial hyperoxia in a model of progressive cerebral ischemia

We investigated the changes in brain oxygen tension (ptiO(2)) after ventilation with pure O-2 in order to (1) clarify the pathophysiology of O-2 exchange in the cerebral microcirculation; and (2) investigate the relationship between brain O-2 tension, O-2 delivery, and consumption in steady-state conditions during stepwise cerebral blood flow (CBF) reductions. A swine model was developed to reduce CBF in three stable steps: (1) baseline (CBF 100%), (2) CBF of 50-60% of baseline, and (3) CBF of (30% of baseline. CBF was reduced by infusing saline into the left lateral ventricle through a catheter connected with an infusion pump. At each step, hyperoxia was tested by increasing the inspired oxygen fraction up to 100%, PtiO(2) reflected the CBF reductions, since it was respectively 27.95 ( +/-10.15), 14.77 (+/-3.58), and 3.45 (+/-2.89) mm Hg during the three CBF steps. Hyperoxia was followed by an increase in ptiO(2), although the increase was significantly lower when hyperoxia was applied during progressive ischemia. O-2 supply to the brain did not change during hyperoxia. Arteriovenous oxygen difference (AVDO(2)) decreased during the phases of intact CBF and moderate impairment, but not during the phase of severe CBF reduction. In conclusion, ptiO(2) reductions closely reflect the imbalance between oxygen delivery and demand; this implies a link between low ptiO(2) and defective O-2 supply due to impaired CBF. However, this relation is not necessarily reciprocal, since manipulating brain oxygen tension does not always influence brain oxygen delivery, as in the case of ventilation with pure oxygen

Diagnóstico e alternativas para a recuperação ambiental da Bacia Hidrográfica do Rio Guandu (BHRG) - RJ.

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Mineralogical evolution of cement pastes at early ages based on thermogravimetric analysis (TGA)

[EN] Ordinary thermogravimetric analysis (TG) and high-resolution TG tests were carried out on three different Portland cement pastes to study the phases present during the first day of hydration. Tests were run at 1, 6, 12 and 24 h of hydration, in order to determine the phases at these ages. High-resolution TG tests were used to separate decompositions presented in the 100¿200 C interval. The non-evaporable water determined by TG was used to determine hydration degree for the different ages. The effect of particle size distribution (PSD) on mineralogical evolution was established, as well as the addition of calcite as mineralogical filler. Finer PSD and calcite addition accelerate the hydration process, increasing the hydration degree on the first day of eaction between water and cement. According to high-resolution TG results, it was demonstrated that ettringite was the only decomposed phase in the 100¿200 C interval during the first 6 h of hydration for all studied cements. C-S-H phase starts to appear in all cements after 12 h of hydration.Funding was provided by Colciencias (Grant No. Convocatoria 567-2012).Gaviria, X.; Borrachero Rosado, MV.; Paya Bernabeu, JJ.; Monzó Balbuena, JM.; Tobón, J. (2018). Mineralogical evolution of cement pastes at early ages based on thermogravimetric analysis (TGA). Journal of Thermal Analysis and Calorimetry. 132(1):39-46. https://doi.org/10.1007/s10973-017-6905-0S39461321Benboudjema F, Meftah JM, Torernti F. Interaction between drying, shrinkage, creep and cracking phenomena in concrete. Eng Struct. 2005;27:239–50.Holt E. Contribution of mixture design to chemical and autogenous shrinkage of concrete at early ages. Cem Concr Res. 2005;35:464–72.Darquennes A, Staquet S, Delplancke-Ogletree MP, Espion B. Effect of autogenous deformation on the cracking risk of slag cement concretes. Cem Concr Compos. 2011;33:368–79.Slowik V, Schmidt M, Fritzsch R. Capillary pressure in fresh cement-based materials and identification of the air entry value. Cem Concr Compos. 2008;30(7):557–65.Evju C, Hansen S. Expansive properties of ettringite in a mixture of calcium aluminate cement, Portland cement and ß-calcium sulfate hemihydrates. Cem Concr Res. 2001;31:257–61.Bentz DP, Jensen OM, Hansen KK. Olesen, Stang, H. Haecker, C.J. Influence of cement particle-size distribution on early age autogenous strain and stresses in cement-based materials. J Am Ceram Soc. 2001;84(1):129–35.Barcelo L, Moranville M, Clavaud B. Autogenous shrinkage of concrete: a balance between autogenous swelling and self-desiccation. Cem Concr Res. 2005;35(1):177–83.Bouasker M, Mounanga P, Turcry P, Loukili A, Khelidj A. Chemical shrinkage of cement pastes and mortars at very early age: effect of limestone filler and granular inclusions. Cem Concr Compos. 2008;30(1):13–22.Bentz DP. A review of early-age properties of cement-based materials. Cem Concr Res. 2008;38(2):196–204.Ozawa T. Controlled rate thermogravimetry. New usefulness of controlled rate thermogravimetry revealed by decomposition of polyimide. J Therm Anal Calorim. 2000;59:375–84.Ramachandran VS, Paroli RM, Beaudoin JJ, Delgado AH. Thermal analysis of construction materials. Building materials series. New York: Noyes Publications; 2003.Zanier A. High-resolution TG for the characterization of diesel fuel additives. J Therm Anal Calorim. 2001;64:377–84.Tobón JI, Payá J, Borrachero MV, Restrepo OJ. Mineralogical evolution of Portland cement blended with silica nanoparticles and its effect on mechanical strength. Constr Build Mater. 2012;36:736–42.Singh M, Waghmare S, Kumar V. Characterization of lime plasters used in 16th century Mughal Monument. J Archeol Sci. 2014;42:430–4.Majchrzak-Kuçeba I. Thermogravimetry applied to characterization of fly ash-based MCM-41 mesoporous materials. J Therm Anal Calorim. 2012;107:911–21.Silva ACM, Gálico DA, Guerra RB, Legendre AO, Rinaldo D, Galhiane MS, Bannach G. Study of some volatile compounds evolved from the thermal decomposition of atenolol. J Therm Anal Calorim. 2014;115:2517–20.Rios-Fachal M, Gracia-Fernández C, López-Beceiro J, Gómez-Barreiro S, Tarrío-Saavedra J, Ponton A, Artiaga R. Effect of nanotubes on the thermal stability of polystyrene. J Therm Anal Calorim. 2013;113:481–7.Yamarte L, Paxman D, Begum S, Sarkar P, Chambers A. TG measurement of reactivity of candidate oxygen carrier materials. J Therm Anal Calorim. 2014;116:1301–7.Borrachero MV, Payá J, Bonilla M, Monzó J. The use of thermogravimetric analysis technique for the characterization of construction materials. The gypsum case. J Therm Anal Calorim. 2008;91(2):503–9.Tobón JI, Payá J, Borrachero MV, Soriano L, Restrepo OJ. Determination of the optimum parameters in the high resolution thermogravimetric analysis (HRTG) for cementitious materials. J Therm Anal Calorim. 2012;107:233–9.Kuzielova E, Žemlička M, Másilko, J, Palou, M.T. Effect of additives on the performance of Dyckerhoff cement, Class G, submitted to simulated hydrothermal curing. J Therm Anal Calorim. Accepted 29 Oct 2017Genc M, Genc ZK. Microencapsulated myristic acid–fly ash with TiO2 shell as a novel phase change material for building application. J Therm Anal Calorim. Accepted 24 Oct 2017.Singh M, Kumar SV, Waghmare SA. The composition and technology of the 3–4th century CE decorative earthen plaster of Pithalkhora caves, India. J Archeol Sci. 2016;7:224–37.Liu L, Liu Q, Cao Y, Pan WP. The isothermal studies of char-CO2 gasification using the high-pressure thermo-gravimetric method. J Therm Anal Calorim. 2015;120:1877–82.Majchrzak-Kuce I, Bukalak-Gaik D. Regeneration performance of metal–organic frameworks TG-vacuum tests. J Therm Anal Calorim. 2016;125:1461–6.Ion RM, Radovici C, Fierascu RC, Fierascu I. Thermal and mineralogical investigations of iron archaeological Materials. J Therm Anal Calorim. 2015;121:1247–53.Rupasinghe M, San Nicolas R, Mendis P, Sofi M, Ngo T. Investigation of strength and hydration characteristics in nano-silica incorporated cement paste. Cem Concr Compos. 2017;80:17–30.Esteves PL. On the hydration of water-entrained cement–silica systems: combined SEM, XRD and thermal analysis in cement pastes. Thermochim Acta. 2011;518:27–35.Riesen R. Adjustment of heating rate for maximum resolution in TG and TMA (MaxRes). J Therm Anal. 1998;53:365–74.Lim S, Mondal P. Micro- and nano-scale characterization to study the thermal degradation of cement-based materials. Mater Charact. 2014;92:15–25.Gill PS, Sauerbrunn SR, Crowe BS. High resolution thermogravimetry. J Therm Anal. 1992;38:255–66.Mounanga P, Khelidj A, Loukili A, Baroghel-Bouny V. Predicting Ca(OH)2 content and chemical shrinkage of hydrating cement pastes using analytical approach. Cem Concr Res. 2004;34:255–65.Zeng Q, Li K, Fen-chong T, Dangla P. Determination of cement hydration and pozzolanic reaction extents for fly-ash cement pastes. Constr Build Mater. 2012;27:560–9.Parrott LP, Geiker M, Gutteridge WA, Killoh D. Monitoring Portland cement hydration: Comparison of methods. Cem Concr Res. 1990;20:919–26.Hewlett PC. Lea’s chemistry of cement and concrete. 4th ed. Oxford: Elsevier Science & Technology Books; 2004.ASTM C305 Standard practice for mechanical mixing of hydraulic cement pastes and mortars of plastic consistency. ASTM International, West Conshohocken, PA; 2012.Taylor HF. Cement chemistry. 2nd ed. Westminster: Thomas Telford; 1997.Nadelman EI, Freas DJ, Kurtis KE. Nano- and microstructural characterization of Portland limestone cement paste. In: Nanotechnology in construction. Proceedings of NICOM 5. 2015. p. 87–92

Identification of soluble protein fragments by gene fragmentation and genetic selection

We describe a new method, which identifies protein fragments for soluble expression in Escherichia coli from a randomly fragmented gene library. Inhibition of E. coli dihydrofolate reductase (DHFR) by trimethoprim (TMP) prevents growth, but this can be relieved by murine DHFR (mDHFR). Bacterial strains expressing mDHFR fusions with the soluble proteins green fluroscent protein (GFP) or EphB2 (SAM domain) displayed markedly increased growth rates with TMP compared to strains expressing insoluble EphB2 (TK domain) or ketosteroid isomerase (KSI). Therefore, mDHFR is affected by the solubility of fusion partners and can act as a reporter of soluble protein expression. Random fragment libraries of the transcription factor Fli1 were generated by deoxyuridine incorporation and endonuclease V cleavage. The fragments were cloned upstream of mDHFR and TMP resistant clones expressing soluble protein were identified. These were found to cluster around the DNA binding ETS domain. A selected Fli1 fragment was expressed independently of mDHFR and was judged to be correctly folded by various biophysical methods including NMR. Soluble fragments of the cell-surface receptor Pecam1 were also identified. This genetic selection method was shown to generate expression clones useful for both structural studies and antibody generation and does not require a priori knowledge of domain architecture

Do women ⩾50 years of age need as much screening as women <50 years after they have had negative screening results?

To assess the adequacy of a routine screening to identify cervical intraepithelial neoplasia 2 or worse (CIN2+) in women over 50 years of age, a retrospective cohort was set in six Italian organised population-based screening programmes. In all, 287 330 women (1 714 550 person-years of observation, 1110 cases) screened at age 25–64, with at least two cytological screening tests, the first negative, were followed from their first negative smear until a biopsy proven CIN2+ lesion or their last negative smear. For women aged 25–49 and 50–64 years, crude and age-standardised detection rate (DR), cumulative risk (CR), adjusted hazard risk for number of previous negative screens, probability of false-positive CIN2+ after two or more smear tests were calculated. Detection rate is significantly lower over 50 years of age. Multivariable analysis shows a significant protective effect from four screening episodes (DR=0.70, 95% CI: 0.51–0.97); the effect of age ⩾50 is 0.29 (95% CI: 0.24–0.35). The CR of CIN2+ is at least eightfold higher in women <50 (CR=2.06, 95% CI: 1.88–2.23) after one previous negative test than in women ⩾50 years with four screens (CR=0.23, 95% CI: 0.00–0.46). Over 50 years of age, after four tests at least three false-positive cases are diagnosed for every true positive. Benefits arising from cytological screening is uncertain in well-screened older women