Resonance Raman enhancement by the intralayer and interlayer electron-phonon processes in twisted bilayer graphene.

Twisted bilayer graphene is a fascinating system due to the possibility of tuning the electronic and optical properties by controlling the twisting angle [Formula: see text] between the layers. The coupling between the Dirac cones of the two graphene layers gives rise to van Hove singularities (vHs) in the density of electronic states, whose energies vary with [Formula: see text]. Raman spectroscopy is a fundamental tool to study twisted bilayer graphene (TBG) systems since the Raman response is hugely enhanced when the photons are in resonance with transition between vHs and new peaks appear in the Raman spectra due to phonons within the interior of the Brillouin zone of graphene that are activated by the Moiré superlattice. It was recently shown that these new peaks can be activated by the intralayer and the interlayer electron-phonon processes. In this work we study how each one of these processes enhances the intensities of the peaks coming from the acoustic and optical phonon branches of graphene. Resonance Raman measurements, performed in many different TBG samples with [Formula: see text] between [Formula: see text] and [Formula: see text] and using several different laser excitation energies in the near-infrared (NIR) and visible ranges (1.39-2.71 eV), reveal the distinct enhancement of the different phonons of graphene by the intralayer and interlayer processes. Experimental results are nicely explained by theoretical calculations of the double-resonance Raman intensity in graphene by imposing the momentum conservation rules for the intralayer and the interlayer electron-phonon resonant conditions in TBGs. Our results show that the resonant enhancement of the Raman response in all cases is affected by the quantum interference effect and the symmetry requirements of the double resonance Raman process in graphene.

On the kinematics-wave motion of living particles in suspension.

This work presents theoretical and experimental analyses on the kinematics-wave motion of suspended active particles in a biological fluid. The fluid is an active suspension of nematodes immersed in a gel-like biological structure, moving at a low Reynolds number. The nematode chosen for the study is Caenorhabditis elegans. Its motion is subjected to the time reversibility of creeping flows. We investigate how this worm reacts to this reversibility condition in order to break the flow symmetry and move in the surrounding fluid. We show that the relationship between the length of an individual nematode and the wavelength of its motion is linear and can be fitted by a theoretical prediction proposed in this work. We provide a deep discussion regarding the propulsion mechanics based on a scaling analysis that identifies three major forces acting on an individual nematode. These forces are a viscous force, a yield stress force due to gelification of agar molecules in the gel-like medium, and a bending force associated with the muscular tension imposed by the nematodes in the medium. By the scalings, we identify the most relevant physical parameters of the nematode's motion. In order to examine and quantify the motion, dynamical system tools such as FFT are used in the present analysis. The motion characterization is performed by examining (or studying) two different populations: (i) in the absence of food with starving nematodes and (ii) with well-fed nematodes. In addition, several kinematic quantities of the head, center of mass, and tail for a sample of nematodes are also investigated: their slip velocities, wavelengths, trajectories, frequency spectra, and mean curvatures. The main findings of this work are the confirmation of a linear relationship between the nematode's physical length and its motion wavelength, the identification of secondary movements in high frequencies that helps breaking the time-reversibility in which the worms are bonded, and the observation and interpretation of a systematic difference between the individual motion of well-fed and starving nematodes.

Determination of uncertainties associated to the in vivo measurement of iodine-131 in the thyroid.

Intakes of radionuclides can be estimated through in vivo measurements, and the uncertainties associated to the measured activities should be clearly stated in monitoring program reports. This study aims to evaluate the uncertainties of in vivo monitoring of iodine 131 in the thyroid. The reference values for high-energy photons are based on the IDEAS Guide. Measurements were performed at the In Vivo Monitoring Laboratory of the Institute of Radiation Protection and Dosimetry (IRD) and at the Internal Dosimetry Laboratory of the Regional Center of Nuclear Sciences (CRCN-NE). In both institutions, the experiment was performed using a NaI(Tl) 3''3″ scintillation detector and a neck-thyroid phantom. Scattering factors were calculated and compared in different counting geometries. The results show that the technique produces reproducibility equivalent to the values suggested in the IDEAS Guide and measurement uncertainties is comparable to international quality standards for this type of in vivo monitoring.

Protective Profile Involving CD23/IgE-mediated NO Release is a Hallmark of Cutaneous Leishmaniasis Patients from the Xakriabá Indigenous Community in Minas Gerais, Brazil.

In this study, we described, for the first time, specific aspects of an anti-Leishmania immune response in a Brazilian Xakriabá indigenous community. Induction of an intracellular NO pathway, triggered by the binding of IgE to CD23 receptor in IFN-γ/IL-4 cytokines environment, was evaluated in localized cutaneous leishmaniasis (LCL) carriers and positive Montenegro skin test (MST) individuals without skin lesion (MT(+) SL(-)). Our data demonstrated that the higher frequency of CD23(+) CD14(+) monocytes and the increased serum levels of IgE observed in the LCL group were even higher in LCL carriers with late lesions (LCL≥60). Furthermore, patients with LCL presented increased NO production after Leishmania (Viannia) braziliensis stimulation and this NO profile was independent of the time of the lesion (recent LCL<60 or late LCL≥60). We also showed that the increased frequency of IFN-γ(+) and IL-4(+) CD4(+) T cells is related to the MT(+) SL(-) group. The results of biomarker signature curves demonstrated that in the MT(+) SL(-) group, the index signature was characterized by DAF-2T(+) CD14(+)/IL-4(+) CD8(+)/IFN-γ(+) CD4(+)/IL-4(+) CD4(+). On the other hand, the LCL group presented a higher index of DAF-2T(+) CD14(+)/CD23(+) CD14(+)/IL-4(+) CD8(+), associated with a lower index of IFN-γ(+) CD8(+). Considering the time of lesion, data analysis demonstrated that the main differences observed were highlighted in LCL<60 patients, with a higher index of CD23(+) CD14(+), which was also present in LCL≥60 patients. In conclusion, our data suggest that the protective immune response involving CD23-IgE-mediated NO release is a hallmark of patients with LCL. However, in MT(+) SL(-) individuals, another different leishmanicidal mechanism seems to be involved.

Kidney transplantation: evaluation and clinical outcome of 237 recipients at low, medium, high, or strong immunological risk of rejection.

BACKGROUND: Donor-specific antibodies (DSAs) play a fundamental role in kidney transplantation. The identification of DSAs is an essential rejection parameter. PATIENTS AND METHODS: We evaluated a protocol in 237 patients receiving kidneys from living (LDs) and deceased donors (DDs). Recipients were classified as being at low (LR), medium (MR), high (HR), or strong (SR) risk of rejection based on Luminex panel reactive antibody (PRA)-single antigen beads (SABs). Grafts that survived for 1 year were evaluated. RESULTS: Of the 237 transplanted patients, 129 (54.43%) received a kidney from an LD and 108 (45.57%) from a DD. Of 95 LR recipients receiving kidneys from LDs, 2 patients lost the graft due to non-immunological causes. Of 34 MR recipients, 13 had rejection episodes, and 2 lost the graft by AMR and one by cellular rejection (CR). Of 108 recipients receiving a kidney from a DD, 59 (54.63%) were LR, 31 (28.70%) MR, 11 (10.19%) HR, and 7 (6.48%) SR. Twenty of all transplanted recipients lost their grafts; 4 were due to clinical causes, 4 by cellular rejection, and 12 by antibody-mediated rejection (AMR) with PRA-SAB mean fluorescent intensity of 530 to 12,591. One-year graft survival for LD transplanted LR and MR patients was 97.6% and 94.1%, respectively (P = .004). In DD recipients, the LR vs MR SD was P = .011, and for LR vs HR + SR it was P = .001. For MR vs HR+SR no SD was found (P = .323). CONCLUSION: Rejections were detected in 51 patients (21.52%). Graft failure occurred in 16 patients (6.75%). A total of 218 (91.98%) recipients maintained good kidney function after 1 year. This protocol based on fluxogram risk assessment of AMR provided fast and precise immunological evaluation of recipients and donors and stratification by immunological risk of AMR.

Experimental investigation on thermo-magnetic convection inside cavities.

This paper presents experimental results on thermo-magnetic convection inside cavities. We examine the flow induced by convective currents inside a cavity with aspect ratio near the unity and the heat transfer rates measurements inside a thin cavity with aspect ratio equal to twelve. The convective unstable currents are formed when a magnetic suspension is subjected to a temperature gradient combined with a gradient of an externally imposed magnetic field. Under these conditions, stratifications in the suspension density and susceptibility are both important effects to the convective motion. We show a comparison between flow patterns of magnetic and gravitational convections. The impact of the presence of a magnetic field on the amount of heat extracted from the system when magnetic and gravitational effects are combined inside the test cell is evaluated. The convection state is largely affected by new instability modes produced by stratification in susceptibility. The experiments reveal that magnetic field enhances the instability in the convective flow leading to a more effective mixing and consequently to a more statistically homogenous temperature distribution inside the test cell. The experimental results allow the validation of the scaling law proposed in a previous theoretical work that has predicted that the Nusselt number scales with the magnetic Rayleigh number to the power of 1/3, in the limit in which magnetic force balances viscous force in the convective flow.

Magnetic-induced migration in a sedimenting suspension of magnetic spherical particles.

We study the relative trajectories of two magnetic spheres interacting in a dilute suspension in the presence of particle inertia and Brownian motion effect. The particles settle relative to one another under the action of gravity and when in close contact they exert on each other a magnetic force and torque due to a permanent magnetization. The balance equations of forces and torques for the two particles are considered in the present formulation. The numerical simulations are based on direct computations of the hydrodynamic and the magnetic interactions among the rigid spheres in the regime of no-null Stokes number. The behavior of these suspensions is examined based on the relative trajectories calculated for several initial configurations. The calculations show that fluctuations in particle orientation produced by the continuous magnetic interactions and by the Brownian motion exerts a significant effect on the understanding of particle aggregation and particle migration in magnetic suspensions.

Self-sampling for human papillomavirus (HPV) testing as cervical cancer screening option. Experience from the LAMS study.

PURPOSE: To compare Hybrid Capture II (HC2) in detecting high-risk (HR) HPV in patient-collected vaginal samples with those obtained using gynaecologist collected samples. METHODS: Patients were submitted to Pap smears, visual inspection with acetic acid (VIA) and HC2 for hr-HPV. RESULTS: A total of 1,081 HC2 tests for HR-HPV were performed: 770 (71.2%) samples were collected by a physician and 311 (28.8%) were self-collected by the patients. In detecting any cervical lesion, the sensitivity of HC2 collected by a physician was higher (92.86%) than that (37.5%) in the self-sampling group. Negative predictive value (NPV) was high for both, 99.69% and 93.75%, respectively. Using the CIN2 cutoff, performance of HC2 was significantly improved: 92.9% and 62.5%, respectively. HC2 specificity for any cervical lesion and for CIN2 or higher were close to 90% in both groups. CONCLUSIONS: Self-sampled HPV testing is a powerful option to increase the detection of cervical lesions in women segregated from prevention programs.

Safety of screening with Human papillomavirus testing for cervical cancer at three-year intervals in a high-risk population: experience from the LAMS study.

OBJECTIVES: To assess whether human papillomavirus (HPV) testing is a safe enough approach to warrant extension of the screening intervals of baseline Papanicolaou (Pap)-/HPV- women in low-income settings. METHODS: Of the >1000 women prospectively followed up as part of the Latin American Screening (LAMS) Study in São Paulo, Campinas, Porto Alegre) and Buenos Aires, 470 women with both baseline cytology and Hybrid Capture 2 (HC2) results available were included in this analysis. These baseline Pap-negative and HC2- or HC2+ women were controlled at six-month intervals with colposcopy, HC2 and Pap to assess the cumulative risk of incident Pap smear abnormalities and their predictive factors. RESULTS: Of the 470 women, 324 (68.9%) were high-risk HPV (hrHPV) positive and 146 (31.1%) were negative. Having two or more lifetime sex partners (odds ratio [OR] = 2.63; 95% CI 1.70-3.51) and women using hormonal contraception (OR = 2.21; 95% CI 1.40-3.51) were at increased risk for baseline hrHPV infection. Baseline hrHPV+ women had a significantly increased risk of incident abnormal Pap smears during the follow-up. Survival curves deviate from each other starting at month 24 onwards, when hrHPV+ women start rapidly accumulating incident Pap smear abnormalities, including atypical squamous cells (ASC) or worse (log-rank; P < 0.001), low-grade squamous intraepithelial lesions (LSIL) or worse (P < 0.001) and high-grade squamous intraepithelial lesions (HSIL) (P = 0.03). Among the baseline hrHPV- women, the acquisition of incident hrHPV during the follow-up period significantly increased the risk of incident cytological abnormalities (hazard ratio = 3.5; 95% CI 1.1-11.7). CONCLUSION: These data implicate that HPV testing for hrHPV types might be a safe enough approach to warrant extension of the screening interval of hrHPV-/Pap-women even in low-resource settings. Although some women will inevitably contract hrHPV, the process to develop HSIL will be long enough to enable their detection at the next screening round (e.g. after three years).

Rastreamento anterior para câncer de colo uterino em mulheres com alterações citológicas ou histológicas / Previous screening for cervical cancer among women with cytological and histological abnormalities

OBJETIVO: Analisar a história de rastreamento citológico anterior em mulheres que apresentaram alterações citológicas e confirmação histológica para câncer cervical. MÉTODOS: Estudo transversal com 5.485 mulheres (15-65 anos) que se submeteram a rastreamento para o câncer cervical entre fevereiro de 2002 a março de 2003, em São Paulo e Campinas, SP. Aplicou-se questionário comportamental e foi feita a coleta da citologia oncológica convencional ou em base líquida. Para as participantes com alterações citológicas indicou-se colposcopia e, nos casos anormais, procedeu-se à biópsia cervical. Para investigar a associação entre as variáveis qualitativas e o resultado da citologia, utilizou-se o teste de qui-quadrado de Pearson com nível de significância de 5 por cento. RESULTADOS: Dentre os resultados citológicos, 354 (6,4 por cento) foram anormais, detectando-se 41 lesões intra-epitelial escamosa de alto grau e três carcinomas; em 92,6 por cento revelaram-se normais. De 289 colposcopias realizadas, 145 (50,2 por cento) apresentaram alterações. Dentre as biópsias cervicais foram encontrados 14 casos de neoplasia intra-epitelial cervical grau 3 e quatro carcinomas. Referiram ter realizado exame citológico prévio: 100 por cento das mulheres com citologia compatível com carcinoma, 97,6 por cento das que apresentaram lesões intra-epiteliais de alto grau, 100 por cento daquelas com confirmação histológica de carcinoma cervical, e 92,9 por cento das mulheres com neoplasia intra-epitelial cervical grau 3. A realização de citologia anterior em período inferior a três anos foi referida, respectivamente, por 86,5 por cento e 92,8 por cento dessas participantes com alterações citológicas e histológicas. CONCLUSÕES: Entre as mulheres que apresentaram confirmação histológica de neoplasia intra-epitelial cervical grau 3 ou carcinoma e aquelas que não apresentaram alterações histológicas não houve diferença estatisticamente significante do número de exames...

OBJECTIVE: To examine previous Pap smear history in women screened for cervical cancer with cytological or histological abnormalities. METHODS: Cross-sectional study in a sample of 5,485 women (15-65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. A behavioral questionnaire was applied and cervical specimens were obtained for testing by Pap smears or liquid-based cytology. Women who had abnormal cytology were referred for colposcopic examination and, if abnormal, for cervical punch biopsy. To explore factors associated to cervical abnormalities Pearson's chi-was conduted square test at a 5 percent significance level. RESULTS: Cytological abnormalities were found in 354 women (6.4 percent) and included 41 high-grade squamous intra-epithelial lesions and 3 carcinomas; 92.7 percent were normal results. Colposcopy was performed in 289 women, and 145 (50.2 percent) showed abnormal results. Punch biopsies showed 14 cervical intraepithelial neoplasias grade 3 and 4 carcinomas. Previous Pap smears were reported in all women who had cytology suspected of carcinoma, 97.6 percent of those with high-grade squamous intra-epithelial lesions, all women with histological diagnosis of carcinoma and 92.9 percent of those who had cervical intraepithelial neoplasias grade 3 histologically. Previous Pap smear in the last tree years was reported by 86.5 percent and 92.8 percent of women with abnormal cytology and biopsy, respectively. CONCLUSIONS: There was no statistically significant difference regarding the number of Pap tests and time since their last test between women with histologically diagnosed carcinoma and cervical intraepithelial neoplasia grade 3 compared with those with normal cytology.

Drug addiction is not an independent risk factor for oncogenic human papillomavirus infections or high-grade cervical intraepithelial neoplasia: case-control study nested within the Latin American Screening study cohort.

Drug abuse (addiction) has been listed among the risk factors for human papillomavirus (HPV) infections, but no case-control studies exist to rule out sexual behaviour and other potential confounders. The aim of this study is to evaluate the role of drug addiction as an independent predictor of HR-HPV infections and (cervical intraepithelial neoplasia) CIN2+ in an age-matched case-control (1:4) study nested within the prospective Latin American Screening (LAMS) study cohort. All 109 women in the LAMS cohort (n=12,114) reporting drug abuse/addiction were matched with four controls (n = 436) of non-abusers strictly by age. Conditional logistic regression analysis was used to estimate the co-variates of drug abuse, and the whole series (n=545) was analysed for predictors of HR-HPV and CIN2+ using univariate and multivariate regression models. Oncogenic HPV infections were significantly (P=0.019) more prevalent among abusers (37.7%) than in controls (21.9%), but there was no difference in high-grade squamous intraepithelial lesions (P=0.180) or CIN2+ lesions (P=0.201). In multivariate conditional logistic regression, number of lifetime sexual partners (P=0.0001), ever smokers (P=0.0001), non-use of OCs (P=0.013), ever having sexually transmitted diseases (STD) (P=0.041) and no previous Pap smear (P=0.027) were independent co-variates of drug addiction. Drug abuse was not an independent risk factor of high-risk (HR)-HPV infection, which was significantly predicted by (1) age below 30 years (P=0.045), (2) more than five lifetime sexual partners (P=0.046) and (3) being current smoker (P=0.0001). In multivariate model, only HR-HPV infection was an independent risk factor of CIN2+ (P=0.031), with adjusted OR=11.33 (95% CI 1.25-102.50). These data indicate that drug addiction is not an independent risk factor of either HR-HPV infections or CIN2+, but the increased prevalence of HR-HPV infections is explained by the high-risk sexual behaviour and smoking habits of these women.

[Previous screening for cervical cancer among women with cytological and histological abnormalities]. / Rastreamento anterior para câncer de colo uterino em mulheres com alterações citológicas ou histológicas.

OBJECTIVE: To examine previous Pap smear history in women screened for cervical cancer with cytological or histological abnormalities. METHODS: Cross-sectional study in a sample of 5,485 women (15-65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. A behavioral questionnaire was applied and cervical specimens were obtained for testing by Pap smears or liquid-based cytology. Women who had abnormal cytology were referred for colposcopic examination and, if abnormal, for cervical punch biopsy. To explore factors associated to cervical abnormalities Pearson's chi-square test was conducted at a 5% significance level. RESULTS: Cytological abnormalities were found in 354 women (6.4%) and included 41 high-grade squamous intra-epithelial lesions and 3 carcinomas; 92.7% were normal results. Colposcopy was performed in 289 women, and 145 (50.2%) showed abnormal results. Punch biopsies showed 14 cervical intraepithelial neoplasias grade 3 and 4 carcinomas. Previous Pap smears were reported in all women who had cytology suspected of carcinoma, 97.6% of those with high-grade squamous intra-epithelial lesions, all women with histological diagnosis of carcinoma and 92.9% of those who had cervical intraepithelial neoplasias grade 3 histologically. Previous Pap smear in the last tree years was reported by 86.5% and 92.8% of women with abnormal cytology and biopsy, respectively. CONCLUSIONS: There was no statistically significant difference regarding the number of Pap tests and time since their last test between women with histologically diagnosed carcinoma and cervical intraepithelial neoplasia grade 3 compared with those with normal cytology.

Prediction of high-grade cervical disease with human papillomavirus detection in women with glandular and squamous cytologic abnormalities.

The objective of this study was to assess whether human papillomavirus (HPV) detection with hybrid capture II (HC II) can help predict the presence and the nature, glandular or squamous, of histologic cervical lesions in women referred due to atypical glandular cells (AGC) or high-grade squamous intraepithelial lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a histologic assessment of their cervix. Histologic analysis showed 38 women with (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%) glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost 70% of AGC-HPV-negative patients did not have a pathologically proven cervical neoplasia, whereas 76% of women with AGC-HPV-positive result were diagnosed with a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV detection did not contribute to their differentiation from glandular lesions. We conclude that in women with AGC, HPV positivity strongly correlated with the presence of glandular or squamous cervical lesion but did not help distinguishing women with squamous from those with glandular neoplasia.

Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: experience from the Latin American Screening study.

Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was carried out in a cohort of 4284 women at their first clinical visit. Overall prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20 years to only 11.0% among those older than 41 years. HPV prevalence was significantly higher among current smokers (odds ratio [OR] = 1.31; 95% CI 1.1-1.6), in women with two or more lifetime sexual partners (OR = 1.9; 95% CI 1.6-2.4), and those women with two or more sexual partners during the past 12 months prior to examination (OR = 1.6; 95% CI 1.2-2.2). HPV detection increased in parallel with increasing cytologic abnormality, being highest in women with high-grade squamous intraepithelial lesion (P= 0.001). Specificity of the HPV test in detecting histologically confirmed cervical disease was 85% (95% CI 83.9-86.1). Sensitivity of the HPV test in detecting histologic abnormalities increased in parallel with disease severity, ranging from 51.5% for cervical intraepithelial neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective decline of positive predictive value. These data suggest that HPV testing with HC II assay might be a viable screening tool among this population with relatively high prevalence of cervical disease.

Atypical glandular cells: criteria to discriminate benign from neoplastic lesions and squamous from glandular neoplasia.

OBJECTIVE: To evaluate the presence of some criteria in cervical smears with atypical glandular cells and their correlation with histological patterns to identify pre-neoplastic and neoplastic lesions. METHODS: Seventy-three women referred with an atypical glandular cell smear, who had undergone conization or hysterectomy, were included in this study. Referral Pap smears were reviewed using the set of 27 cyto-morphological criteria that was correlated with the histological diagnosis. RESULTS: Histological results showed intraepithelial or invasive neoplasia in 35 (48%) cases and benign lesions in 38 (52%) cases. After logistic regression and decision tree analysis an increased nuclear/cytoplasmic ratio and the presence of dyskeratotic cells were strongly associated with intraepithelial or invasive neoplasia and the differential cyto-morphological criteria for glandular lesions were decreased cytoplasm, irregular nuclear membranes and the presence of nucleoli. CONCLUSION: The analysis of individual cyto-morphological criteria can better predict intraepithelial or invasive neoplasia and differentiate glandular from squamous lesions.

Evaluation of visual inspection with acetic acid (VIA), Lugol's iodine (VILI), cervical cytology and HPV testing as cervical screening tools in Latin America. This report refers to partial results from the LAMS (Latin AMerican Screening) study.

OBJECTIVES: To assess the performance indicators of visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI) in four Latin American centres participating in the ongoing Latin AMerican Screening (LAMS) study, in settings with moderate incidence of cervical disease and with poorly to moderately well-organized cervical cancer screening. SETTING: Three Brazilian centres (São Paulo, Campinas and Porto Alegre) and one Argentine centre (Buenos Aires) recruited a total of 11,834 healthy women to undergo VIA, VILI, conventional Pap smear and Hybrid Capture II (HCII). METHODS: Women who had a positive result from any of these tests were subjected to colposcopy and biopsies (if necessary), and women with high-grade cervical intraepithelial neoplasia (CIN) were properly treated. To control for verification bias, 5% of women with normal tests were referred for colposcopy, as were 20% of HCII-negative women. RESULTS: Data on VIA (n=11,834), VILI (n=2994), conventional Pap smear (n=10,138) and HCII (n=4195) were available for test comparisons, calculating sensitivity, specificity, and positive and negative predictive values. Overall test positivity was 11.6% for VIA, 23.0% for VILI, 2.2% for Pap smear (LSIL threshold), 1.1% for Pap smear (HSIL threshold) and 17.1% for HCII. VIA was positive in 61.8% of the women with CIN 1, 57.0% of those with CIN 2, 35.0% of women with CIN 3 and in 21 of 28 (75%) of women with cancer. Approximately 10% of women with no detectable disease had an abnormal VIA. Regarding VILI, 83.3% of women diagnosed with CIN 1 and 62.5% of those with CIN 3 had an abnormal test. VILI failed to detect one of three cases of cancer. Both the sensitivity, specificity and positive predictive value of VIA and VILI in detecting CIN 2 or CIN 3 could be significantly improved depending on the combination with Pap smear or HCII (sensitivity up to 100.0% and specificity up to 99.8%). CONCLUSIONS: The LAMS study failed to reproduce the performance figures obtained with VIA and VILI (as stand-alone tests) in some other settings, where the prevalence of cervical disease was higher. However, a combined use of VIA or VILI with the Pap test or HCII allowed specific detection of cervical abnormalities.

Comparing PAP smear cytology, aided visual inspection, screening colposcopy, cervicography and HPV testing as optional screening tools in Latin America. Study design and baseline data of the LAMS study.

OBJECTIVES: This is a European Commission (EC)-funded ongoing study known as the LAMS (Latin American Screening) study, where PAP smear/liquid-based cytology and screening colposcopy were compared with i) three optional screening tools [visual inspection with acetic acid (VIA), or Lugol's iodine (VILI), cervicography] and with ii) Hybrid Capture II from a) conventional samples and from b) self-samples, in women at different risk for cervical cancer in Brazil and Argentina. STUDY DESIGN: During 2002-2003, a cohort of 12,107 women attending four clinics: Campinas (CA), Sao Paulo (SP), Porto Alegre (PA) and Buenos Aires (BA), were interviewed for risk factors, and examined using the 8 diagnostic arms. Colposcopy was performed for women positive in any test and for 5% of women with baseline PAP-negative and 20% of HCII-negatives. All high-grade lesions (CIN2/3) were treated, and low-grade CIN are prospectively followed-up. RESULTS: Of the 12,107 women, the following baseline data are available: epidemiological data (n=11,996), conventional PAP smears (n=10,363), LBC, SurePATH (n=320), LBC, DNA-Citoliq (n=1,346), VIA (n=12.067), VILI (n=3,061), cervicography (n=279), screening colposcopy (n=3,437), HCII conventional (n=4,710), HCII self-sampling (n=246) and cervical biopsies (n=1,524). The four sub-cohorts differ significantly in all their baseline data on the implicated risk factors of cervical cancer, consonant with their origin from regions with different cancer incidence. Around 95% of all PAP smears were negative, with slight variations in the prevalence of LSIL and HSIL between the four centers. Significant differences were found in the detection rates of abnormal findings in VIA, VILI and colposcopy between the four centers (p=0.0001). The prevalence of HPV was practically identical (16.5-18.8%) in all four cohorts (p=0.486), with no differences in the relative viral loads. Biopsy results were different depending on whether the women underwent screening colposcopy (BA) or elective colposcopy (others). CONCLUSION: Four cohorts with significantly different baseline data are available, and prospective follow-up of these women permits analysis of whether variations in cervical cancer incidence in these regions is due to i) different natural history of the precursor lesions, or ii) due to different levels of exposure to the known risk factors.