To report the impact of the release of the 2002 American Society for Colposcopy and Cervical Pathology guidelines on the management of abnormal cytological findings on time to diagnosis of cervical cancer in an insured population. This retrospective study identified women with cervical cancer (invasive and carcinoma in situ) through commercially insured administrative claims data. The cervical cancer case definition required a claim for cervical cancer and a claim with a diagnostic procedure (colposcopy, conization, biopsy, or hysterectomy). Time to diagnosis was defined as days between the initial Pap screening and the diagnostic procedure. Between 1999 and 2004, there were 3,325 women aged 18 to 64 years who met the case definition for cervical cancer. Median time to diagnosis decreased from 42 days (interquartile range = 23-93 d) to 36.5 days (interquartile range = 20.5-80 d) for women with invasive cancer after the guideline change. The number of follow-up Pap screenings before biopsy also decreased (p =.0067). Among women with carcinoma in situ whose initial Pap screening was completed by a family practice clinician, time to diagnosis was projected to be more than 9 days longer compared with those whose screening was performed by a gynecologist. The 2002 American Society for Colposcopy and Cervical Pathology guidelines for the management of abnormal cytological findings seem to have had a positive impact on the time to diagnosis and Pap screening use before biopsy for women diagnosed with cervical cancer.

BACKGROUND Data on the adherence to surgical site infection (SSI) prevention guidelines in Italian cardiac surgery units are lacking. METHODS A multiple-choice questionnaire, structured into eight sections following the Centers for Disease Control 1999 (CDC) guidelines, was prepared and sent to 24 surgical units participating in a national study group (GIS-InCard); this units perform over 20% of all cardiac surgical procedures in Italy. Answers were stratified based upon the evidence of the recommendations: grade IA (ten questions), grade IB (52 questions), grade II (11 questions), and no recommendation (seven questions). RESULTS 17 of the 24 units (72%) returned the questionnaire. Adherence to grade IA recommendations was 69 +/- 34%, with five units (29%) showing a > or =80% adherence. Adherence to grade IB and II was 65 +/- 26% and 71 +/- 28%, respectively. Adherence did not vary significantly depending on the evidence of the recommendation, i.e., grade IA, IB or II (p = 0.72). Low adherence levels to grade I recommendations were observed on hair removal:(1) it was performed systematically in all male patients (0% adherence),(2) it was performed on the morning of the intervention in 29% of centers, and (3) the method of hair removal was adequate in 41% of cases. Despite 94% of units having written guidelines on antibiotic prophylaxis, only 65% administered antibiotic prophylaxis with the correct timing - i.e., on anesthesia induction. CONCLUSIONS Adherence to CDC SSI guidelines in Italy is fair. The evidence of the recommendation does not influence adherence. Organizational improvements, especially those regarding hair removal and the timing of antibiotic prophylaxis, should be implemented in most hospitals.

OBJECTIVE We describe the content of providers' postcolposcopy consultations and women's perceptions of consultations and their conditions. MATERIALS AND METHODS Consultations (n = 47) were audiotaped, transcribed, and analyzed. Women were interviewed immediately after consultations. RESULTS Providers often named or described the diagnosis (n = 46), suggested a return appointment date (n = 41), and asked if women understood the diagnosis or had any questions (n = 40). Risk factors and causes of cervical cancer, including human papillomavirus infection, smoking, and sexual activity, were rarely discussed (n = 5). The majority (n = 40) of women were asked if they understood the provider's explanation or had any questions. Women rated quality of their provider's explanation as high and the severity of and worry about their condition as moderate. CONCLUSIONS Postcolposcopy consultations focused on follow-up screening and treatment. Risk factors and causes of cervical cancer were discussed infrequently.

OBJECTIVE To evaluate whether timely adherence rates differ by race among women with abnormal Pap tests participating in a cost-free or reduced-cost program. METHODS Eligible subjects included women aged 47-64 years who received a referral for follow-up care after an abnormal Pap test from 1999 to 2002 in South Carolina (n=330). Adherence was measured as days to receipt of follow-up care after an abnormal Pap test. Cox proportional hazards modeling was used to estimate risk factors associated with time to adherence within 60 and 365 days by race. RESULTS African-American and non-Hispanic white women had similar adherence to follow-up. Among white women, those with high-grade lesions were less likely to adhere in a timely manner relative to those with low-grade lesions (hazard ratio 0.6, 95% confidence interval [CI] 0.4-1.0). For African-American women, rural residence (hazard ratio: 0.5, 95% CI 0.2-0.9) and history of abnormal Pap tests (hazard ratio 0.6, 95% CI 0.3-1.0) were associated with decreased adherence, whereas less education (hazard ratio 2.3, 95% CI 1.3-3.9) was associated with increased adherence. CONCLUSION Adherence rates do not differ by race. However, risk factors for adherence within race are variable. Interventions tailored to the differential needs of racial and ethnic groups may prove effective toward increasing timely adherence rates. LEVEL OF EVIDENCE II.

OBJECTIVE Approximately 4000 women annually will die from preventable and treatable cervical cancer. Failure to adhere to follow-up recommendations after an abnormal Pap test can lead to development of cervical cancer. This paper summarizes the body of literature on adherence to follow-up after an abnormal Pap test in order to facilitate development of interventions to decrease morbidity and mortality due to cervical cancer. METHODS We conducted a comprehensive search of published literature addressing risk factors for adherence or interventions to improve adherence following an abnormal Pap test as the outcome. We included peer-reviewed original research conducted in the United States from 1990 to 2005. RESULTS Fourteen analytical and twelve experimental studies that met our criteria were reviewed. Lesion severity and health beliefs were consistently associated with adherence rates. Communication interventions, including telephone reminders, counseling, and educational sessions, increased follow-up compliance across intervention studies. Inconsistent evidence for associations among race, income, and age were found. CONCLUSIONS Further research is needed to reinforce current studies addressing health beliefs and social support. Interventions that focus on the interplay among psychological, educational, and communication barriers are necessary. These interventions should be adapted and applied across various racial/ethnic and socioeconomic groups to reach all women with a high-risk profile for invasive cervical cancer.

OBJECTIVE To address socio-demographic factors associated with adherence to follow-up recommendations in a high-risk population of women referred for follow-up care after an abnormal Pap test. METHODS 486 women aged 46-64 served by BCCEDP in two southeastern states between 1999-2002 and referred for follow-up care after an abnormal Pap test were the sampling frame for this cross-sectional study; 204 women completed a phone-based interview in 2004. Cox proportional hazards modeling was used to determine the association of various risk factors with time to adherence. RESULTS Among those completing the phone interview (interview rate=61.4%) the mean age was 53.3 years, 64.7% were African-American women, 81.9% had low-grade cervical lesions, and all were either uninsured or under insured. Over 95% received follow-up care for an abnormal Pap test within 365 days of referral. When the BCCEDP criteria of follow-up within 60 days were applied, 52.9% were adherent. Rates of self-reported and program documented adherence differed significantly by state. After adjusting for state of residence, women who reported having symptoms of a chronic disease were more likely to be adherent within 365 days (aHR=1.42; 95% CI=1.00, 2.04). Neither age, race, lesion severity, education, number of dependent adults or children, self-perceived physical health, nor smoking status was associated with time to adherence. CONCLUSIONS Findings suggest that institutional factors may be more important than individual factors in predicting time to adherence for an abnormal Pap test.

AIMS: To differentiate between two types of atypical squamous cells of undetermined significance (ASCUS): probably neoplastic (PN) or probably reactive (PR), and, in accordance with the recommendations on screening protocols of the Emilia-Romagna Region (PSRER), Italy, to define the best management to follow and the prognosis. Furthermore, the associations between ASCUS and infectious agents and human papillomavirus (HPV) were evaluated. METHODS: Fifty-eight ASCUS smears were reviewed and sorted; if a diagnosis of ASCUS was confirmed, the smear was classified as PR or PN, and the PSRER group was identified. Then, colposcopy was performed with checks for infectious agents (culture evaluation with cytological or clinical criteria) and HPV (hybrid capture). RESULTS: The ASCUS frequency was 3.96%. Of the 58 cases, 33 (56.9%) were diagnosed as ASCUS on review, of which 15 cases were PN and 18 were PR, while 23 (39.7%) smears were normal and 2 (3.4%) showed cervical intraepithelial neoplasia (CIN). There was a higher frequency of bacterial vaginosis (BV) and HPV in ASCUS PR patients compared with normal cytology, and a higher frequency of CIN in ASCUS PN patients compared with normal controls (P < 0.05). By grouping ASCUS 1 and 3, we observed a higher frequency of CIN and of high-grade colposcopy findings compared with ASCUS 2 and 4 (P < 0.05). From the 23 cases not found to be ASCUS, 18 (87.5%) had normal cytology and colposcopy results on the first follow-up. CONCLUSIONS: Classification of ASCUS as either PN or PR helps in clinical conduct and prognosis, because a higher frequency of CIN is found in ASCUS PN. ASCUS subdivisions, based on PSRER and colposcopy, may facilitate the clinical conduct because ASCUS 1 and 3 with high-grade colposcopic findings proved to be related to the presence of CIN. We propose that initial ASCUS cytology be reviewed, and if it is confirmed, colposcopy should be performed. For those cases found to be normal on review of the cytology results, it is suggested that a cytological check-up be carried out every 6 months.

Although studies have addressed psychosocial factors associated with obtaining follow-up care for an abnormal Pap test, none have explored the effect of stressful life events in predicting the receipt of follow-up care for an abnormal Pap test. Data from a program (1995-2001) that provided free follow-up care for women with low-grade cervical lesions (n = 601) was used to determine whether life stressors increased risk of study discontinuation. Women were interviewed at baseline and offered follow-up at 4- to 6-month intervals for up to 24 months. Of the 556 women recruited and interviewed (92% response rate), 53 were referred out because they had high-grade cervical lesions and 33 had a health condition precluding follow-up. Among 470 women who began follow-up, 175 (37.2%) discontinued before completing three visits. Women who discontinued were significantly more likely to report more stressful life events in the past year [age-adjusted relative risk (aRR), 1.19; 95% confidence interval (95% CI), 1.08-1.30; 17-item scale]. Events most strongly associated with discontinuation included having a problem with a boss (aRR, 1.9; 95% CI, 1.5-2.4), severe physical partner violence (aRR, 1.7; 95% CI, 1.3-2.2), being homeless (aRR, 2.1; 95% CI, 1.6-2.8), and having an unplanned pregnancy (aRR, 1.5, 95% CI, 1.2-2.1). Life stressors may be important predictors of discontinuation of free follow-up care among women in need of immediate follow-up care to prevent lesion progression.

BACKGROUND We wanted to explore the conceptual representations of illness and experiences with care among women who have learned of an abnormal Papanicolaou (Pap) smear result. METHODS The study took place in 2 primary care, family practice clinics serving low-income, multiethnic patients in the Bronx, New York City. We conducted qualitative, semistructured telephone interviews with 17 patients who had recently learned of abnormal findings on a Pap smear. After a preliminary coding phase, the investigators identified 2 important outcomes: distress and dissatisfaction with care, and factors affecting these outcomes. A model was developed on a subset of the data, which was then tested on each transcript with an explicit search for disconfirming cases. A revised coding scheme conforming to the dimensions of the model was used to recode transcripts. RESULTS Women reported complex, syncretic models of illness that included both biomedical and folk elements. Many concerns, especially nonbiomedical concerns, were not addressed in interactions with physicians. An important source of both distress and dissatisfaction with care was the women's lack of understanding of the inherent ambiguity of Pap smear results. When perceived care needs, which included emotional support as well as information, were not met, distress and dissatisfaction were greatly increased. CONCLUSION In this study, patients' illness models and expectations of care were not routinely addressed in their conversations with physicians about abnormal Pap smear results. When physicians can take the time to review patients' illness models carefully, distress and dissatisfaction with care can be reduced considerably.

Besides all the confusion and associated problems that the use of ASC has created, it has initiated substantial investigational interest that has resulted in a better understanding of squamous intraepithelial lesions and the biology of cervical neoplasia. Although the category of ASC has created, and will continue to create, controversy in the diagnostic and management fields, it allows the pathologist to convey uncertainty that may be the result of poor sampling or difficulty in interpretation of a case. It is a valuable tool that the cytopathologist can use to make it known that the Papanicolaou test has its limitations and may need and benefit, in some instances, from support from ancillary studies. Similar limitations are recognized in other areas of pathology and the use of immunohistochemistry or molecular studies is widely accepted as an aid to a more specific and definitive interpretation. The time for the Papanicolaou test to be considered similarly has arrived. HPV DNA testing may not be the perfect test for cervical cancer screening because of high prevalence of HPV infection in the general population; however, it is currently the best-studied ancillary test and has been proven to be cost-effective for the triage of Papanicolaou tests with equivocal squamous cells. It is important for the cytopathologist to have well-developed diagnostic skills in interpreting gynecologic preparations, and to classify cases as ASC only when deemed appropriate. Downgrading cytologic findings that are diagnostic of a squamous intraepithelial lesion to ASC with the hope of supporting it by an HPV test will only result in a devaluation of the Papanicolaou test. Such recourse may, however, be acceptable in specific situations, such as in patients who have complex histories, atypical clinical presentations, or during pregnancy. Quality assurance measures to closely monitor the ASC:SIL ratio and the rate of HPV positivity in ASC cases will be essential to ensure the appropriate use of this interpretive category. The coordination of the 2001 Bethesda and ASCCP consensus meetings resulted in the new subcategories of ASC-US and ASC-H, along with well-defined management strategies for these interpretations. This new and clinically relevant terminology should lead to a reduction in difficulties at the clinical level and a more uniform management of patients, unlike the situation following Bethesda 1991 where the gynecologist was faced with a new "diagnosis" without specific management recommendations. The standardization of reporting and clinical management will also allow more reliable evaluation of patient outcomes and cost analysis. The 2002 American Cancer Society guidelines did not make specific recommendations regarding HPV DNA testing for the triage of patients who have a cytology result of ASC-US [64]. The FDA approved the expanded use of HPV testing in conjunction with the Papanicolaou test for cervical cancer screening in March of 2003. The future is likely to bring additional testing modalities that may be more specific for detecting squamous lesions that are more likely to persist or progress to carcinoma, than the currently available HPV tests. In addition, looking to the more distant future, recently published data from HPV vaccine trials suggests that immunizing women who are negative for HPV-16 may eventually reduce the incidence of cervical cancer [65]. At the present, however, the most effective method to decrease the mortality of this disease process is to make sure that all women have access to, and receive, effective cervical cytologic screening.

OBJECTIVE: To determine factors predictive of failure to return for colposcopy among women with significant abnormalities on Papanicolaou smears in a high-risk clinical population. DESIGN: Telephone survey. SETTING: An urban community health center. PARTICIPANTS: Two hundred seventy-nine women randomly selected from all women seen at the health center with abnormal Papanicolaou smears requiring colposcopy during 1993 to 1994. Six (2%) refused participation, and 19% could not be reached for inclusion. Subjects were mostly minority women receiving Medicaid. MAIN OUTCOME MEASURE: Completion of colposcopy. RESULTS: Of the 279 selected women, 79% were interviewed. The rate of adherence with colposcopy was 75% for the respondents. Women who did not know the results of their smear or who incorrectly understood their results were significantly less likely to return for colposcopy (P =.001). Younger women, especially teenagers, were less likely to return (P =.02). Socioeconomic status, education, primary language, health beliefs, fear of cancer, and clinician's gender or discipline were not associated with rate of follow-up. Barriers involving transportation, child care, and insurance also did not predict follow-up. CONCLUSIONS: Effective communication of results is the most important factor related to follow-up after abnormal Papanicolaou smear in this setting. In other settings, other factors may be of greater importance.

BACKGROUND AND OBJECTIVES: Clinicians in community health centers find it difficult to balance the demands of increased productivity and effective teaching. We hypothesized that precepting third-year students would decrease clinical productivity and that many elements related to the quality of the learning experience (e.g., amount of patient contact, student autonomy) would be adversely affected by pressure to see increasing numbers of patients. METHODS: Students and preceptors in a 6-week family medicine clerkship completed daily surveys that measured the presence of quantifiable elements of the ambulatory teaching experience. They also rated the overall quality of learning during each session. RESULTS: For 62 sessions for which both students and preceptors completed evaluations, students rated the overall quality of learning more highly than preceptors. For students, the elements most positively associated with quality of learning were total teaching time and the frequency with which family issues were raised. For preceptors, the elements that predicted quality of learning were the number of patients that students saw independently and total teaching time. The clinical productivity of preceptors did not differ for sessions with and without a student. CONCLUSIONS: Preceptors can be effective teachers who encourage student autonomy and who model behaviors central to family practice, without decreasing productivity.

CONTEXT Universal tuberculin skin testing of children has been shown to be costly and inefficient. In response, several authorities have recommended targeted screening based on epidemiological risk. In 1996, the New York City Department of Health (NYCDOH) developed questions to identify children who require a tuberculin skin test. OBJECTIVE To determine the sensitivity, specificity, and predictive validity of the NYCDOH tuberculosis risk assessment questionnaire. DESIGN Prospective criterion standard study in which tuberculin skin tests and the NYCDOH questionnaire were administered simultaneously between August 1996 and January 1998. Specific questions asked about contact with a tuberculosis case, birth in or travel to endemic areas, regular contact with high-risk adults, and human immunodeficiency virus infection in the child. SETTING Ambulatory clinic in South Bronx, New York, NY. PARTICIPANTS Consecutive sample of 2920 children aged 1 to 18 years. MAIN OUTCOME MEASURES Sensitivity, specificity, positive and negative predictive values of the questionnaire, and odds ratio (OR) of reactive skin test results. RESULTS The NYCDOH questionnaire identified 413 children (14%) as having at least 1 risk factor. Of these, 23 (5.6%) had a positive skin test result; 4 (0.16%) of the 2507 without risk factors had a positive result. Results for the full NYCDOH questionnaire were sensitivity, 85.2%; specificity, 86.0%; negative predictive value, 99.8%; positive predictive value, 5.4%; and OR, 35.2 (95% confidence interval, 12.1-102.4). CONCLUSION The NYCDOH questionnaire is a valid instrument for identifying children for tuberculin skin testing.

STUDY OBJECTIVES: To assess the validity of purified protein derivative (PPD) readings by patients and trained health-care professionals as compared with a calibrated model. DESIGN AND PARTICIPANTS: Survey of a group of patients, nurses, medical assistants, and physicians at five neighborhood health centers in the Bronx, NY. INTERVENTIONS: Participants were asked to read a calibrated model with four PPD indurations measuring 0 mm, 3 mm, 7 mm, and 13 mm. Indurations > or = 5 mm were to be considered "positive" reactions. MEASUREMENTS AND RESULTS: Data were obtained from 233 patients and 80 trained professionals. All patients correctly measured the 0-mm induration site and were able to detect the presence of an induration in 99.3% of possible observations. Compared with professionals, patients had more variability in measurements and interpretations of the 3-, 7-, and 13-mm sites. Professionals detected 100% of all indurations. Patients' specificity for the 0- and 3-mm sites was 97.4% and 62.7%, respectively; whereas sensitivity for the 7- and 13-mm sites was 68.2% and 89.3%, respectively. Professionals' specificity for the 0- and 3-mm sites was 98.7% and 65.3%, respectively; their sensitivity for the 7- and 13-mm sites was 86.7% and 97.3%, respectively. Seventy percent of professionals agreed that the model was a realistic representation of PPD indurations. CONCLUSIONS: Patients can reliably distinguish between the presence and absence of an induration at a PPD injection site. They are not as reliable in the measurement and interpretation of test reactions. Professionals had considerable variability in their assessments of PPDs but were more precise overall in their assessments than patients.

Many people on the waiting list for organ donation die each year without receiving organs. The shortage of organs is even more pronounced in minority communities. Despite the fact that minorities are at higher risk, they may be less likely to support or consent to organ donation. This investigation was undertaken to study racial factors in organ donation, by focusing on differences in awareness, attitudes, and behavior. Three family practice centers in the Bronx with racially diverse but socioeconomically homogenous communities were studied. The study population consisted of a convenience sample of 163 patients who were approached for participation while they waited to see a doctor. Respondents filled out a 25-item survey that measured demographic information; their exposure to, awareness of, and attitudes toward organ donation; and whether they had signed an organ donor card. The results demonstrated overwhelming support for organ donation across all racial groups. Racial differences were found on awareness of and attitudes toward organ donation, and in the signing of organ donation cards. In contrast to other studies, racial minorities were not less likely than whites to support organ donation. These results suggest that making it easier for racial minorities to obtain organ donor cards could increase their rates of consenting to donate organs.

Extracellular proteins play a key role in generating and maintaining cohesion and adhesion in biological tissues. These "natural glues" are involved in vital biological processes such as blood clotting, wound healing and maintaining the structural integrity of tissues. Macromolecular assemblies of proteins can be functionally stabilized in a variety of ways in situ that include ionic interactions as well as covalent crosslinking to form protein networks that can extend both within and between tissues. Within tissues, myriad cohesive forces are required to preserve tissue integrity and function, as are additional appropriate adhesive forces at interfaces both within and between tissues of differing composition. While the mechanics of some key structural adhesive proteins have been characterized in tensile experiments at both the macroscopic and single protein levels, the fracture toughness of thin proteinaceous interfaces has never been directly measured. Here, we describe a novel and simple approach to measure the cohesive behavior and toughness of thin layers of proteinaceous adhesives. The test is based on the standard double-cantilever beam test used for engineering adhesives, which was adapted to take into account the high compliance of the interface compared to the beams. This new "rigid double-cantilever beam"(RDCB) method enables stable crack propagation through an interfacial protein layer, and provides a direct way to measure its full traction-separation curve. The method does not require any assumption for the shape of the cohesive law, and the results provide abundant information contributing to understanding the structural, chemical and molecular mechanisms acting in biological adhesion. As an example, we present results using this method for thin films of fibrin - a protein involved in blood clotting and used clinically as a tissue bio-adhesive after surgery - with the effects of calcium and crosslinking by Factor XIII being examined. Finally, a simple model is proposed demonstrating how a bell-shaped cohesive law forms during the failure of the fibrin interface based on an eight-chain model whose structure degrades and changes configuration with stress.2.

BACKGROUND Thousands of rescue and recovery workers descended on the World Trade Center (WTC) in the wake of the terrorist attack of September 11, 2001 (9/11). Recent studies show that respiratory illness and post-traumatic stress disorder (PTSD) are the hallmark health problems, but relationships between them are poorly understood. The current study examined this link and evaluated contributions of WTC exposures. METHOD Participants were 8508 police and 12 333 non-traditional responders examined at the WTC Medical Monitoring and Treatment Program (WTC-MMTP), a clinic network in the New York area established by the National Institute for Occupational Safety and Health (NIOSH). We used structural equation modeling (SEM) to explore patterns of association among exposures, other risk factors, probable WTC-related PTSD [based on the PTSD Checklist (PCL)], physician-assessed respiratory symptoms arising after 9/11 and present at examination, and abnormal pulmonary functioning defined by low forced vital capacity (FVC). RESULTS Fewer police than non-traditional responders had probable PTSD (5.9% v. 23.0%) and respiratory symptoms (22.5% v. 28.4%), whereas pulmonary function was similar. PTSD and respiratory symptoms were moderately correlated (r=0.28 for police and 0.27 for non-traditional responders). Exposure was more strongly associated with respiratory symptoms than with PTSD or lung function. The SEM model that best fit the data in both groups suggested that PTSD statistically mediated the association of exposure with respiratory symptoms. CONCLUSIONS Although longitudinal data are needed to confirm the mediation hypothesis, the link between PTSD and respiratory symptoms is noteworthy and calls for further investigation. The findings also support the value of integrated medical and psychiatric treatment for disaster responders.

Genetic map construction and identification of quantitative trait loci (QTLs) for blackleg resistance were performed for four mapping populations derived from five different canola source cultivars. Three of the populations were generated from crosses between single genotypes from the blackleg-resistant cultivars Caiman, Camberra and (AV)Sapphire and the blackleg-susceptible cultivar Westar(10). The fourth population was derived from a cross between genotypes from two blackleg resistant varieties (Rainbow and (AV)Sapphire). Different types of DNA-based markers were designed and characterised from a collection of 20,000 EST sequences generated from multiple Brassica species, including a new set of 445 EST-SSR markers of high value to the international community. Multiple molecular genetic marker systems were used to construct linkage maps with locus numbers varying between 219 and 468, and coverage ranging from 1173 to 1800 cM. The proportion of polymorphic markers assigned to map locations varied from 70 to 89% across the four populations. Publicly available simple sequence repeat markers were used to assign linkage groups to reference nomenclature, and a sub-set of mapped markers were also screened on the Tapidor x Ningyou (T x N) reference population to assist this process. QTL analysis was performed based on percentage survival at low and high disease pressure sites. Multiple QTLs were identified across the four mapping populations, accounting for 13-33% of phenotypic variance (V (p)). QTL-linked marker data are suitable for implementation in breeding for disease resistance in Australian canola cultivars. However, the likelihood of shifts in pathogen race structure across different geographical locations may have implications for the long-term durability of such associations.

For skeletal mineralization, the avian embryo mobilizes calcium from its calcitic eggshell. This occurs through dissolution of specific interior regions of the shell in a process that also weakens the shell to allow hatching. Here, we have examined eggshell ultrastructure during dissolution occurring between laying of a fertilized egg (with incubation) and hatching of the chick (Gallus gallus). We have focused on changes in shell mammillae where the majority of dissolution takes place. Using scanning electron microscopy, we describe differences in matrix-mineral structure and relationships not observed in unfertilized eggs (unresorbed eggshell). We document changes in the calcium reserve body - an essential sub-compartment of mammillae - consistent with it being an early, primary source of calcium essential for embryonic skeletal growth. Dissolution events occurring in the calcium reserve sac and in the base plate of the calcium reserve body, and similar changes in surrounding bulk mammillae structure, all correlate with advancing skeletal embryonic calcification. The changes in mammillae sub-structures can generally be characterized as mineral dissolutions revealing fine surface topographies on remaining mineral surfaces and the exposure of an extensive, intracrystalline (occluded) organic matrix network. We propose that this mineral-occluded network regulates how shell mineral is dissolved by providing dissolution channels facilitating calcium release for the embryonic skeleton.

In trabecular bone fracture repair in vivo, osteogenesis occurs through endochondral ossification under hypoxic conditions, or through woven bone deposition in the vicinity of blood vessels. In vitro osteogenesis assays are routinely used to test osteoblastic responses to drugs, hormones, and biomaterials for bone and cartilage repair applications. These cell culture models recapitulate events that occur in woven bone synthesis, and are carried out using primary osteoblasts, osteoblast precursors such as bone marrow-derived mesenchymal stromal cells (BMSCs), or various osteoblast cell lines. With time in culture, cell differentiation is typically assessed by examining levels of alkaline phosphatase activity (an early osteoblast marker) and by evaluating the assembly of a collagen (type I)-containing fibrillar extracellular matrix that mineralizes. In this review, we have made a comparative analysis of published osteogenic assays using calvarial cells, calvaria-derived cell lines, and bone marrow stromal cells. In all of these cell types, alkaline phosphatase activity shows similar progression over time using a variety of osteogenic and mineralizing media conditions; however, levels of alkaline phosphatase activity are not proportional to observed mineralization levels.

PURPOSE: The study's purposes were to identify the portfolio of grants awarded by the National Cancer Institute that addressed follow-up to abnormal screening tests for colon, breast and cervical cancer, document key research design characteristics, and discuss questions and issues for future practice and research.METHODS: A standardized form was used to audit grants funded from 2002 through 2011. Grant text was independently reviewed by two auditors; differences in reports were discussed until consensus was reached. The investigators then summarized findings in order to distill trends and issues.RESULTS: Twelve grants met inclusion criteria; 5, 4, 2 and 1 addressed follow-up of Pap tests, mammography, and colorectal tests and multiple screens respectively. Fifty percent were R01 awards, the majority of which applied group or individual RCT designs. One was a prospective cohort study. R21s typically emphasized qualitative methods and stressed behavioral epidemiology, measurement tool development and intervention planning; several listed aims related to determining prevalence. Definition of outcome measures was variable: e.g. completion of a follow-up test; time to follow-up; and steps until diagnosis. Four studies explicitly focused on ethnic/racial disparities; 5 on low income and underserved populations. Several emphasized measurement development. Three included cost analyses research questions. Most focused on individual level change, although changes in the broader multi-level context were proposed, but at times implicit, often viewed as process measures. A majority included aims related to understanding important mediator and moderator variables. Few explicated multilevel theories, although models reflected an ecological orientation.CONCLUSIONS: Future practice and research priorities include development of clear operational definitions of follow-up; conceptual and descriptive evaluations of how providers, patients, and organizations interact across the steps and interfaces of follow-up care; determination of priorities for multilevel intervention testing and improvement of measures, and application of appropriate and innovative study designs using multi-methods.This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.

OBJECTIVE This population based study investigates the patterns of care women with high grade cervical dysplasia receive. METHODS The study population includes women with a first time diagnosis of a high grade dysplasia (ASC-H, AGUS, HSIL, malignancy, carcinoma) from 2000 to 2005 as identified in a centralized cervical smear database. Record linkages were then carried out to other databases of health care services to characterize management. RESULTS Women (43,712) with a high grade dysplasia had a mean age of 37.6. HSIL and AGC accounted for 55% and 33% of abnormalities, respectively. The mean time to referral to colposcopy services ranged from 6 to 24 weeks. Women (1195) were diagnosed with an underlying cervical cancer with a mean time to diagnosis of 26, 26, 17, 6, and 3 weeks for the cytologic abnormality of ASC-H, AGUS, HSIL, malignancy, and carcinoma, respectively. Women (559) were diagnosed with endometrial cancer. The mean time to diagnosis from index Pap was 16, 5.3 and 1.5 weeks for AGC, malignancy, and carcinoma on Pap test, respectively. The percentage of patients with a high grade Pap smear who had no follow-up all up to a 2-year window from index Pap was 5.4, 74, 19, 1.22, and 0.18% for ASC-H, AGUS, HSIL, malignancy and carcinoma on Pap, respectively. CONCLUSIONS The mean time to referral to colposcopy and rates of loss to follow-up for high grade smears are influenced by cytologic nomenclature. Explicit language is recommended for national guidelines to reduce the prolonged time in the workup of patients who may have serious premalignant and malignant lesion of the reproductive tract.

OBJECTIVE: To investigate epidemiological factors that predicts high-risk human papillomavirus (HR-HPV) types among women with atypical squamous cells of undetermined significance (ASCUS). METHODS: Case-control study of women with ASCUS and 'reflex' HR-HPV DNA test results at the Prentice Ambulatory Care (PAC) outpatient clinic, Northwestern University, Chicago, USA. Univariate analysis and logistic regression were done to generate measures of association between various epidemiological variables and positive HR-HPV. RESULTS: A total of 2,539 women had liquid-based Pap smear and 126 (4.96%) were confirmed ASCUS. Of the 126 with ASCUS, 125 (99.2%) had 'reflex' HR-HPV results. The prevalence of HR-HPV among women with ASCUS was 43.2%. Among the 54 with a positive HR-HPV, 76.0% were women <30 years and 24.0% were >/=30 years. The prevalence of HR-HPV was 61.2% among women <30 years versus 22.4% among women >/=30 years (P < 0.001). The mean age and standard deviations (SD) was 26.5 (6.2 years) and 34.6 (10.2 years) for women with a positive HR-HPV and negative HR-HPV test, respectively (P < 0.001). Age category <30 years was independently predictive of HR-HPV (adjusted odds ratio 4.6, 95% CI 2.0-10.7; P < 0.001). CONCLUSION: Age <30 years significantly predicts presence of HR-HPV types among women with diagnosis of ASCUS. A strategy of limiting HPV testing to older women and referral of those <30 years for colposcopic assessment appears more effective.

BACKGROUND: DNA- and mRNA-based assays are the main tools used for detecting human papillomavirus (HPV) nucleic acid in clinical samples. A recent tool, NucliSENS EasyQ HPV, uses a new concept to directly detect the expression of HPV oncogenic factors (E6 and E7) from the most prevalent HPV genotypes in cervical cancer (16, 18, 31, 33 and 45). OBJECTIVES: The primary aim of the study is to assess the accuracy of NucliSENS EasyQ HPV in detecting high-risk (HR) HPV in a population of atypical cells of undetermined significance/low-grade squamous intraepithelial lesion/high-grade squamous lesion (ASCUS/LSIL/HSIL) patients using a clinical cut-off of a cervical dysplasia (CIN2+) histology. The secondary aim is to compare this mRNA-based assay with the DNA-based hybrid capture II (HCII) assay. STUDY DESIGN: The study population comprised 140 women referred for colposcopy and histology. NucliSENS EasyQ HPV test, hybrid capture II (HCII) test and linear array (LA) test were assessed on all samples. All the tests were performed on the samples collected in PreservCyt liquid media for liquid-based cytology (ThinPrep Pap test). RESULTS: The clinical specificity of the NucliSENS EasyQ HPV was 63% for the detection of CIN2+ or HSIL patients, significantly higher than the specificity of HCII and LA (49% and 45%, respectively, p<0.05). Agreement between HCII and NucliSENS EasyQ HPV was fair (k=0.49) and was good between HCII and LA (k=0.88). HPV 16 was the most-detected type (49% with NucliSENS EasyQ HPV and 56% with LA), and HPV 31 was the second most-detected HPV type (31% with NucliSENS EasyQ HPV and 29% with LA). CONCLUSIONS: The NucliSENS EasyQ HPV assay has interesting clinical sensitivity and specificity for the detection of HPV types in CIN2+ patients and shows comparable diagnostic values with the HCII DNA assay. This assay allows simultaneous detection of HPV mRNA and determination of the type of the main prevalent oncogenic virus.

OBJECTIVE To evaluate the value of cervical cytology and hybrid capture II (HC- II) human papillomavarus (HPV) test for screening cervical lesion. METHODS Conventional papanicolaou (Pap) smear by improved take-samples, liquid-based cytology test (LCT) and HC- II human papillomavarus test were performed in 425 women in Shang Mei-lin community of Futian region in Shenzhen city, from December 2007 to March 2008 and the above methods were performed in 75 women in Shenzhen Hospital of Peking University at the same time. Age stratified sampling was used. Samples of Pap were taken a broom-type sampling device (take-samples used for LCT) with split-sampling method. Those women with HPV-positive, Pap> or =atypical squamous cells of undetermined sign (ASCUS) or LCT> or =ASCUS received multi-spot biopsy and endocervical curettage under colposcopy. Final diagnosis would depend on pathological findings as well, to evaluate the values of Pap, LCT, HC-II HPV, Pap-HPV parallel test, LCT-HPV parallel test, Pap-HPV serial test and LCT-HPV serial test for the screening program on cervical cancer. RESULTS (1) In this study, 7 women had cervical intraepithelial neoplasia (CIN) II, another 7 had CIN III, 1 had cervical cancer in the community; 9 had CIN II, 11 had CIN III, 3 had cervical cancer in the hospital, respectively.(2) The sensitivity of HC-II HPV and cytology-HPV parallel test for detecting > or =CIN II was >95.0% while negative pre-value were nearly 100.0%.(3) There were no significant differences of screening effectiveness and unsatisfactory rates between Pap of improved take-samples and LCT.(4) The cost-effectiveness ratio of Pap-HPV parallel test was higher than LCT-HPV parallel test. CONCLUSION It was suggested that the first choice for screening of cervical serious lesion were HC-II HPV and cytology-HPV parallel test while Pap-HPV parallel test was the best method for screening purposes.

BACKGROUND Cervical cancer screening guidelines were substantially revised in 2002 and 2003. Little information is available about primary care physicians' current Papanicolaou (Pap) test screening practices, including initiation, frequency, and stopping. OBJECTIVE To assess current Pap test screening practices in the United States. DESIGN Cross-sectional survey. SETTING Nationally representative sample of physicians during 2006 to 2007. PARTICIPANTS 1212 primary care physicians. MEASUREMENTS The survey included questions about physician and practice characteristics and recommendations for Pap screening presented as clinical vignettes describing women by age and by sexual and screening histories. A composite measure-guideline-consistent recommendations-was created by using responses to vignettes in which major guidelines were uniform. RESULTS Most physicians reported providing Pap tests to their eligible patients (91.0%[95% CI, 89.0% to 92.6%]). Among Pap test providers (n = 1114), screening practices, including number of tests ordered or performed, use of patient reminder systems, and cytology method used, varied by physician specialty (P < 0.001). Although most Pap test providers reported that screening guidelines were very influential in their clinical practice, few had guideline-consistent recommendations for starting and stopping Pap screening across multiple vignettes (22.3%[CI, 19.9% to 25.0%]). Guideline-consistent recommendations varied by specialty (obstetrics/gynecology, 16.4%; internal medicine, 27.5%; and family or general practice, 21.1%). Compared with obstetricians/gynecologists, internal medicine specialists and family or general practice specialists were more likely to have guideline-consistent screening recommendations (odds ratio, 1.98 [CI, 1.22 to 3.23] and 1.45 [CI, 0.99 to 2.13], respectively) in multivariate analysis. LIMITATION Physician self-report may reflect idealized rather than actual practice. CONCLUSION Primary care physicians' recommendations for Pap test screening are not consistent with screening guidelines, reflecting overuse of screening. Implementation of effective interventions that focus on potentially modifiable physician and practice factors is needed to improve screening practice. PRIMARY FUNDING SOURCE National Cancer Institute, Centers for Disease Control and Prevention, and Agency for Healthcare Research and Quality.

BACKGROUND Screening for cervical cancer precursors has evolved considerably with the introduction of new technologies to improve the early detection of disease. The objective of this study was to analyze the accuracy and effectiveness of combined screening with cytology and high-risk human papillomavirus (HR-HPV) testing in a low-risk population of women aged >or=30 years. METHODS Consecutive unselected samples from a group of 1871 women aged >or=30 years were screened with image-guided ThinPrep tests and HR-HPV tests during a 6-month period. Histologic follow-up was reviewed among women with positive HR-HPV tests. RESULTS A total of 85 (4.5%) women had positive HR-HPV tests. In 48 HR-HPV-positive women with follow-up biopsies, 41 (85%) were found to have histologic abnormalities. Thirty-three (1.9%) women with cytologically normal Papanicolaou (Pap) tests harbored HR-HPV, and a cervical intraepithelial neoplasia (CIN) 2+ lesion was detected in 1 (16%) of 6 women with histologic follow-up. Conversely, 2 (28%) of 7 women with high-grade intraepithelial lesion on cytology tested negative for HR-HPV during the same period. A case of serous carcinoma with atypical glandular cells on cytology was also negative for HR-HPV, as expected. CONCLUSIONS In this low-risk population of women aged >or=30 years, histology-confirmed CIN2+ lesions were identified in women with negative cytology and positive HR-HPV tests, as well as in those with positive cytology and negative HR-HPV tests. Because both cytology and HPV testing alone missed significant lesions, cotesting with Pap and HR-HPV in women aged >or=30 years appears to be a reasonable option in a low-risk population.

BACKGROUND Human papillomavirus (HPV) DNA testing using Hybrid Capture 2 assay with ThinPrep Papanicolaou (Pap) collection is the only US Food and Drug Administration-approved method for the triage of women with atypical squamous cells of undetermined significance (ASCUS). Although SurePath Pap collection has been used for Hybrid Capture 2 HPV DNA testing, clinical validation of this method has been scarce. METHODS From a cervical cancer-screening program in Mississippi, we analyzed data from screenings of 8380 women with ASCUS Pap results who underwent reflex Hybrid Capture 2 HPV DNA tests during a course of 4 years. Of these, 4145 were screened with the ThinPrep collection system, and 4235 were screened with SurePath. Results of follow-up biopsies within 3 months of Pap tests were available for the ThinPrep group (229 cases) and the SurePath group (455 cases). Hybrid Capture 2 positive rates and the follow-up biopsy results from both groups were compared. RESULTS Hybrid Capture 2 detected high-risk HPV DNA in 68.8% of ThinPrep and 66.7% of SurePath-collected specimens (P =.37). Detection rates for CIN2+ and CIN3+ were also comparable between ThinPrep (21.4%, 3.1%) and SurePath (15.4%, 4.2%) using Hybrid Capture 2 (P =.06, P =.45). In ThinPrep-collected specimens, 4.4% were quantitatively insufficient for Hybrid Capture 2 testing. Significantly more equivocal Hybrid Capture 2 results were observed in SurePath (11.4%) than in ThinPrep specimens (3.2%). However, 67.4% of women with equivocal Hybrid Capture 2 results had negative 1-year Pap cytology follow-up in the SurePath group. CONCLUSIONS Hybrid Capture 2 positive rates and CIN2-3 detection rates were comparable for the SurePath and ThinPrep Pap collection systems, thus supporting the use of SurePath for Hybrid Capture 2 testing.

OBJECTIVE. Atypical squamous cells of undetermined significance (ASCUS) cells, occurring in organized cytological screening, may be either high-risk human papillomavirus (HPV) positive or negative. To refine the assessment of women with ASCUS, a high-risk HPV-DNA test is recommended as triage in Sweden. METHODS: A total of 197 consecutive women (mean age 39 years, range 21-60) with a diagnosis of ASCUS from the primary screening were selected for triage. Their cervical smears were collected and evaluated by using conventional cytological examination in combination with a high-risk HPV-DNA test (hybrid capture 2). The women were categorized into four groups: Group A, Cytology +/HPV +; Group B, Cytology-/HPV +; Group C, Cytology +/HPV-; and Group D, Cytology-/ HPV-. Women within Groups A-C were admitted for colposcopy and cervical biopsy. The women in Group D were considered as a low-risk group for tumor development, and were re-examined after three years in the next round of the organized screening. RESULTS: In women in Group A (n=58) the prevalence of histological verified CIN2-3 was 41%, in Group B (n=41) 20%, and in Group C (n=9) 0%. In Group D (n=89), repeated primary screening three years later revealed CIN2-3 in two biopsies from 74 women studied (<3%). The prevalence of a high-risk HPV infection decreased with age in women with ASCUS. It was 74% in women <30 years and 19% in women > or =50 years. CONCLUSIONS: Adding a high-risk HPV test in secondary screening increased the identification of women with CIN2-3 lesions by 33% in comparison with repeat cytology (p=0.01). The clinical significance of the ASCUS diagnosis varied with age of the women.

STUDY OBJECTIVE To determine the prevalence of cervical dysplasia and adherence to recommendations for referral/follow-up in a group of adolescent girls undergoing routine reproductive health care in a primary care setting. DESIGN Retrospective review of all screening Papanicolaou (Pap) smears performed between 12/99 and 12/05. SETTING An urban academic adolescent medicine practice in New York City. PARTICIPANTS 824 sexually active adolescent girls. MAIN OUTCOMES Cytology and cervical biopsy results and adherence to follow-up and colposcopy recommendations. RESULTS Among 824 adolescents ages 12-21 years (mean = 17) who underwent 1 to 6 screening Paps, 81%(n = 666) had normal Pap smears only and 19%(n = 158) had at least one abnormal Pap. Of the 1214 screening Pap smears reviewed, only one was suggestive of a high grade lesion, 85 (7%) revealed atypical squamous cells of undetermined significance (ASCUS), 81 (6.6%) showed low-grade squamous intraepithelial lesions (LGSIL), and the rest were normal. Fifteen percent of patients (n = 123) were referred for at least one colposcopy; only 72%(n = 88) complied. Biopsy identified 5 high-grade lesions; 3 patients required cervical Loop Electrosurgical Excision Procedures: Despite appropriate referrals and access to services, 32% of patients with ASCUS and 28% of patients with LGSIL lacked evidence of either follow-up Pap or colposcopy by the time of last review. CONCLUSIONS High-grade lesions were rare in our sample, supporting new guidelines for less colposcopy in this age group. Although many adolescents were followed within primary care, achieving appropriate follow-up for those with cervical dysplasia was challenging and often unsuccessful.