A Development and Implementation of a Preconception Counseling Program for Black Women and Men in the Southeastern United States: A Pilot Protocol.

Introduction: Racial/ethnic disparities in maternal mortality rates represent one of the most significant areas of disparities amongst all conventional population perinatal health measures in the U.S. The alarming trends and persistent disparities of outcomes by race/ethnicity and geographic location reinforce the need to focus on ensuring quality and safety of maternity care for all women. Despite complex multilevel factors impacting maternal mortality and morbidity, there are evidence-based interventions that, when facilitated consistently and properly, are known to improve the health of mothers before, during and after pregnancy. The objective of this project is to test implementation of pre-conception counseling with father involvement in community-based settings to improve cardiovascular health outcomes before and during pregnancy in southeastern United States. Methods and Analysis: This study has two components: a comprehensive needs and assets assessment and a small-scale pilot study. We will conduct a community informed needs and assets assessment with our diverse stakeholders to identify opportunities and barriers to preconception counseling as well as develop a stakeholder-informed implementation plan. Next, we will use the implementation plan to pilot preconception counseling with father involvement in community-based settings. Finally, we will critically assess the context, identify potential barriers and facilitators, and iteratively adapt the way preconception counseling can be implemented in diverse settings. Results of this research will support future research focused on identifying barriers and opportunities for scalable and sustainable public health approaches to implementing evidence-based strategies that reduce maternal morbidity and mortality in the southeastern United States' vulnerable communities. Discussion: Findings will demonstrate that preconception counseling can be implemented in community health settings in the southeastern United States. Furthermore, this study will build the capacity of community-based organizations in addressing the preconception health of their clients. We plan for this pilot to inform a larger scaled-up clinical trial across community health settings in multiple southeastern states.

Electronic Cigarette Use During Preconception and/or Pregnancy: Prevalence, Characteristics, and Concurrent Mental Health Conditions.

Background: Electronic cigarettes (e-cigarettes) are increasing in popularity in the United States. Prior prevalence estimates of e-cigarette use in pregnancy range from 1% to 15%. Materials and Methods: We assessed prevalence of e-cigarette and conventional cigarette use during preconception or pregnancy in a large sample of racially/ethnically diverse, low-income pregnant women via telephone survey (2015-2018) and compared sociodemographic characteristics and mental health conditions. Results: Of 1365 pregnant women surveyed, 54 (4.0%) reported e-cigarette use (regardless of other tobacco use), 372 (27.3%) reported conventional cigarette use without e-cigarette use (conventional cigarette use), and 939 (68.8%) reported no tobacco or nicotine replacement therapy (NRT) product use during the preconception period and/or pregnancy. Seventy-four percent of women using e-cigarettes reported also using conventional cigarettes. Women who used e-cigarettes were more likely to report high school education or greater, income <$30,000, White race, and non-Hispanic ethnicity than women who used conventional cigarettes. Women who used e-cigarettes were more likely than women who used conventional cigarettes or no tobacco/NRT to report symptoms of depression. Women who used e-cigarettes and women who used conventional cigarettes were more likely than women who used no tobacco/NRT to report a history of severe mental health conditions, alcohol use during pregnancy, and marijuana or other drug use during preconception. Conclusions: In this sample, 4% of women used e-cigarettes during preconception and/or pregnancy and most also used conventional cigarettes. Increased efforts by providers to screen for tobacco (including use of e-cigarette) and polysubstance use and to provide cessation services could improve outcomes of mothers and children.

Nesting Environment Provides Sex-Specific Neuroprotection in a Rat Model of Neonatal Hypoxic-Ischemic Injury.

Hypoxic-ischemic (HI) encephalopathy is a devastating injury that occurs when the fetal brain is deprived of oxygen and blood to a degree that may lead to neurological damage, seizing and cerebral palsy. In rodents, early environmental enrichment that promotes maternal care-taking behavior (mCTB) can improve neurobehavioral outcomes and protect against neurological decline. We hypothesized that an enhanced nesting environment would improve mCTB as measured by pup weight gain, and support greater HI recovery in developing rats. Pregnant dams (E15-16) were introduced to either control Standard Facility (SF) housing or closed nestbox (CN) conditions and maintained in larger cages through pup weaning. On postnatal day (PND) 7, male and female Long-Evans rat pups (N = 73) were randomly sorted into one of two surgical conditions: control and HI. HI pups received isoflurane anesthesia and right carotid artery ligation, a 2-h rest followed by 90 min exposure to a moist hypoxic (92% N, 8% O2) chamber. Pups (PND 8) were weighed daily, and tested on the Morris Water Maze (MWM) task (PND 35-50). Results demonstrate significant differences afforded to male and female pups based on weight measure, where CN-rearing modifies pre-weaning adolescent weights in females and increases post-weaning weights in males and females by an average of 10 g. Following successful MWM training and acquisition (PND 35-37), both male and female CN-raised animals demonstrated faster latency to find the hidden platform (HP) during HP trials (PND 38-42) and appeared to freely explore the MWM pool during an additional probe trial (PND 43). Moreover, after sacrifice (PND 60), CN rearing created sex-specific alterations in brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF) immunopositive cell staining of the dorsomedial striatum and CA1 of the hippocampus. CN-rearing afforded HI males higher BDNF levels in the striatum and produced greater GDNF levels in the hippocampus of HI-injured females. These results suggest that early life environmental enrichment positively modifies nesting environment, increases weight gain, as well as spatial learning and memory in a sex-specific directionality. Our findings also implicate correlative changes in corticolimbic neurotrophin protein levels in the CN-reared animals that may contribute to these benefits.

The things they carried: The pathogenic effects of old and new parasites following the intercontinental invasion of the Australian cane toad (Rhinella marina).

Brought to Australia in 1935 to control agricultural pests (from French Guiana, via Martinique, Barbados, Jamaica, Puerto Rico and Hawai'i), repeated stepwise translocations of small numbers of founders enabled the cane toad (Rhinella marina) to escape many parasites and pathogens from its native range. However, the infective organisms that survived the journey continue to affect the dynamics of the toad in its new environment. In Australia, the native-range lungworm Rhabdias pseudosphaerocephala decreases its host's cardiac capacity, as well as growth and survival, but not rate of dispersal. The lungworm is most prevalent in long-colonised areas within the toads' Australian range, and absent from the invasion front. Several parasites and pathogens of Australian taxa have host-shifted to cane toads in Australia; for example, invasion-front toads are susceptible to spinal arthritis caused by the soil bacterium, Ochrobactrum anthropi. The pentastome Raillietiella frenata has host-shifted to toads and may thereby expand its Australian range due to the continued range expansion of the invasive toads. Spill-over and spill-back of parasites may be detrimental to other host species; however, toads may also reduce parasite loads in native taxa by acting as terminal hosts. We review the impact of the toad's parasites and pathogens on the invasive anuran's biology in Australia, as well as collateral effects of toad-borne parasites and pathogens on other host species in Australia. Both novel and co-evolved pathogens and parasites may have played significant roles in shaping the rapid evolution of immune system responses in cane toads within their invaded range.

The colour of paternity: extra-pair paternity in the wild Gouldian finch does not appear to be driven by genetic incompatibility between morphs.

In socially monogamous species, individuals can use extra-pair paternity and offspring sex allocation as adaptive strategies to ameliorate costs of genetic incompatibility with their partner. Previous studies on domesticated Gouldian finches (Erythrura gouldiae) demonstrated a genetic incompatibility between head colour morphs, the effects of which are more severe in female offspring. Domesticated females use differential sex allocation, and extra-pair paternity with males of compatible head colour, to reduce fitness costs associated with incompatibility in mixed-morph pairings. However, laboratory studies are an oversimplification of the complex ecological factors experienced in the wild and may only reflect the biology of a domesticated species. This study aimed to examine the patterns of parentage and sex ratio bias with respect to colour pairing combinations in a wild population of the Gouldian finch. We utilized a novel PCR assay that allowed us to genotype the morph of offspring before the morph phenotype develops and to explore bias in morph paternity and selection at the nest. Contrary to previous findings in the laboratory, we found no effect of pairing combinations on patterns of extra-pair paternity, offspring sex ratio or selection on morphs in nestlings. In the wild, the effect of morph incompatibility is likely much smaller, or absent, than was observed in the domesticated birds. Furthermore, the previously studied domesticated population is genetically differentiated from the wild population, consistent with the effects of domestication. It is possible that the domestication process fostered the emergence (or enhancement) of incompatibility between colour morphs previously demonstrated in the laboratory.

Proton magnetic resonance spectroscopy and outcome in term neonates with chorioamnionitis.

OBJECTIVE: Evaluate brain metabolites, which reflect neuroinflammation, and relate to neurodevelopmental outcomes in healthy term neonates exposed to chorioamnionitis. STUDY DESIGN: Thirty-one healthy term neonates with documented fetal inflammatory response after maternal chorioamnionitis underwent magnetic resonance spectroscopy (MRS), with voxels placed in basal ganglia (BG) and frontal white matter. Bayley III examinations were performed at 12 months of age. RESULT: Infants with below average outcomes did not show the same increase in NAA/Cho ratios postnatally as the group with normal outcomes. Decreased NAA/Cho and increased Lac/Cr in BG correlated with lower motor and cognitive composite scores, respectively, controlling for postnatal age. In males, increased lactate/NAA in BG were associated with lower motor scores. Funisitis severity was associated with decreased NAA/Cho and increased mI/NAA in males. CONCLUSION: In healthy term newborns with chorioamnionitis, MRS ratios shortly after birth may provide evidence of occult neuroinflammation, which may be associated with worse performance on 1-year neurodevelopmental tests.

Causes of male sexual trait divergence in introduced populations of guppies.

Males from different populations of the same species often differ in their sexually selected traits. Variation in sexually selected traits can be attributed to sexual selection if phenotypic divergence matches the direction of sexual selection gradients among populations. However, phenotypic divergence of sexually selected traits may also be influenced by other factors, such as natural selection and genetic constraints. Here, we document differences in male sexual traits among six introduced Australian populations of guppies and untangle the forces driving divergence in these sexually selected traits. Using an experimental approach, we found that male size, area of orange coloration, number of sperm per ejaculate and linear sexual selection gradients for male traits differed among populations. Within populations, a large mismatch between the direction of selection and male traits suggests that constraints may be important in preventing male traits from evolving in the direction of selection. Among populations, however, variation in sexual selection explained more than half of the differences in trait variation, suggesting that, despite within-population constraints, sexual selection has contributed to population divergence of male traits. Differences in sexual traits were also associated with predation risk and neutral genetic distance. Our study highlights the importance of sexual selection in trait divergence in introduced populations, despite the presence of constraining factors such as predation risk and evolutionary history.

Sex differences in cerebral blood flow following chorioamnionitis in healthy term infants.

OBJECTIVE: Sex is an important determinant of neonatal outcomes and may have a significant role in the physiologic response to maternal chorioamnionitis. Our goal was to determine cerebral blood flow (CBF) parameters by sex and subsequent neurodevelopment in healthy term infants exposed to chorioamnionitis. STUDY DESIGN: CBF by Doppler ultrasound in anterior and middle cerebral (ACA, MCA) and basilar arteries were analyzed for time-averaged maximum velocity (TAMX) and corrected resistive index in 52 term control and chorioamnionitis-exposed infants between 24 and 72 h after birth. Placental pathology confirmed histologic evidence of chorioamnionitis (HC). Bayley Scales of Infant Development-III were administered at 12 months. RESULT: HC male infants had significantly greater TAMX in the MCA and lower mean MCA and ACA resistance than HC females. Abnormal CBF correlated negatively with neurodevelopmental outcome. CONCLUSION: CBF is altered in term infants with histologically confirmed chorioamnionitis compared with control infants with sex-specific differences.

Comparison of four assays for the detection of cryptococcal antigen.

We compared the performance of four assays for the detection of cryptococcal antigen in serum samples (n = 634) and cerebrospinal fluid (CSF) samples (n = 51). Compared to latex agglutination, the sensitivity and specificity of the Premier enzyme immunoassay (EIA), Alpha CrAg EIA, and CrAg lateral flow assay (LFA) were 55.6 and 100%, 100 and 99.7%, and 100 and 99.8%, respectively, from serum samples. There was 100% agreement among the four tests for CSF samples, with 18 samples testing positive by each of the assays.

Kin selection, not group augmentation, predicts helping in an obligate cooperatively breeding bird.

Kin selection theory has been the central model for understanding the evolution of cooperative breeding, where non-breeders help bear the cost of rearing young. Recently, the dominance of this idea has been questioned; particularly in obligate cooperative breeders where breeding without help is uncommon and seldom successful. In such systems, the direct benefits gained through augmenting current group size have been hypothesized to provide a tractable alternative (or addition) to kin selection. However, clear empirical tests of the opposing predictions are lacking. Here, we provide convincing evidence to suggest that kin selection and not group augmentation accounts for decisions of whether, where and how often to help in an obligate cooperative breeder, the chestnut-crowned babbler (Pomatostomus ruficeps). We found no evidence that group members base helping decisions on the size of breeding units available in their social group, despite both correlational and experimental data showing substantial variation in the degree to which helpers affect productivity in units of different size. By contrast, 98 per cent of group members with kin present helped, 100 per cent directed their care towards the most related brood in the social group, and those rearing half/full-sibs helped approximately three times harder than those rearing less/non-related broods. We conclude that kin selection plays a central role in the maintenance of cooperative breeding in this species, despite the apparent importance of living in large groups.

Treponema-specific tests for serodiagnosis of syphilis: comparative evaluation of seven assays.

The diagnosis of syphilis is challenging and often relies on serologic tests to detect treponemal or nontreponemal antibodies. Recently, the Centers for Disease Control and Prevention and the Association of Public Health Laboratories proposed an update to the syphilis serology testing algorithm, in which serum samples are first tested using a treponema-specific test and positive samples are analyzed with a nontreponemal assay. The goal of this study was to compare the performance of seven treponemal assays (BioPlex 2200 syphilis IgG [Bio-Rad, Hercules, CA], fluorescent treponemal antibody [FTA] assay [Zeus Scientific, Raritan, NJ], Treponema pallidum particle agglutination [TP-PA; Fujirebio Diagnostics, Malvern, PA], Trep-Sure enzyme immunoassay [EIA; Phoenix Biotech, Oakville, Ontario, Canada], Trep-Chek EIA [Phoenix Biotech], Trep-ID EIA [Phoenix Biotech], and Treponema ViraBlot IgG [Viramed Biotech AG, Planegg, Germany]) using serum samples (n = 303) submitted to our reference laboratory. In addition to testing with these 7 assays, all samples were tested by a rapid plasma reagin (RPR) assay and a treponemal IgM Western blot assay (Viramed ViraBlot). Compared to the FTA assay as the gold standard, the evaluated treponemal tests demonstrated comparable levels of performance, with percent agreement ranging from 95.4% (95% confidence interval, 92.3 to 97.3) for the Trep-Sure EIA to 98.4% (96.1 to 99.4) for the Trep-ID EIA. Compared to a "consensus of the test panel" (defined as at least 4 of 7 treponemal tests being in agreement), the percent agreement ranged from 95.7% (92.7 to 97.5) for Trep-Sure to 99.3% (97.5 to 99.9) for Trep-ID. These data may assist clinical laboratories that are considering implementing a treponemal test for screening or confirmatory purposes.

Evaluation of a multiplex flow immunoassay for detection of epstein-barr virus-specific antibodies.

Conventional methods for the detection of Epstein-Barr virus (EBV)-specific antibodies include the immunofluorescence assay (IFA) and enzyme immunoassay (EIA). While sensitive and specific, these methods are labor-intensive and require separate assays for each analyte. This study evaluated the performance of a multiplex bead assay (BioPlex 2200; Bio-Rad Laboratories, Hercules, CA) for the simultaneous detection of immunoglobulin G (IgG) and IgM class antibodies to the EBV viral capsid antigen (VCA) and IgG class antibodies to Epstein-Barr virus nuclear antigen-1 (EBNA-1). Serum specimens (n = 1,315) submitted for routine EBV-specific antibody testing by EIA (Grifols-Quest, Inc., Miami, FL) were also tested by the multiplex bead assay using the BioPlex 2200 automated analyzer. Specimens showing discordant results were tested by IFA. Following IFA resolution, the BioPlex VCA IgM, VCA IgG, and EBNA-1 IgG assays demonstrated 97.9%, 91.4%, and 96.9% agreement, respectively, with the results obtained by EIA. Furthermore, the BioPlex assays showed an overall agreement of 94.1% with the EIA when the specimens were categorized by disease state (susceptible, acute, or past infection) based on the EBV-specific antibody profiles. These findings indicate that the BioPlex EBV assays demonstrate a performance comparable to that of the conventional EIA, while allowing for a more rapid (2.3 h for 100 samples versus 4.5 h by the EIA) and higher-throughput ( approximately 400 samples per 9 h versus 200 samples by the EIA) analysis of the EBV-specific antibody response.

Evaluation of two commercial systems for automated processing, reading, and interpretation of Lyme borreliosis Western blots.

The diagnosis of Lyme borreliosis (LB) is commonly made by serologic testing with Western blot (WB) analysis serving as an important supplemental assay. Although specific, the interpretation of WBs for diagnosis of LB (i.e., Lyme WBs) is subjective, with considerable variability in results. In addition, the processing, reading, and interpretation of Lyme WBs are laborious and time-consuming procedures. With the need for rapid processing and more objective interpretation of Lyme WBs, we evaluated the performances of two automated interpretive systems, TrinBlot/BLOTrix (Trinity Biotech, Carlsbad, CA) and BeeBlot/ViraScan (Viramed Biotech AG, Munich, Germany), using 518 serum specimens submitted to our laboratory for Lyme WB analysis. The results of routine testing with visual interpretation were compared to those obtained by BLOTrix analysis of MarBlot immunoglobulin M (IgM) and IgG and by ViraScan analysis of ViraBlot and ViraStripe IgM and IgG assays. BLOTrix analysis demonstrated an agreement of 84.7% for IgM and 87.3% for IgG compared to visual reading and interpretation. ViraScan analysis of the ViraBlot assays demonstrated agreements of 85.7% for IgM and 94.2% for IgG, while ViraScan analysis of the ViraStripe IgM and IgG assays showed agreements of 87.1 and 93.1%, respectively. Testing by the automated systems yielded an average time savings of 64 min/run compared to processing, reading, and interpretation by our current procedure. Our findings demonstrated that automated processing and interpretive systems yield results comparable to those of visual interpretation, while reducing the subjectivity and time required for Lyme WB analysis.

A retrogen strategy for presentation of an intracellular tumor antigen as an exogenous antigen by dendritic cells induces potent antitumor T helper and CTL responses.

Induction of an effective antitumor response requires CD4+ helper T (Th) cells to recognize antigens on the same dendritic cells (DCs) that cross-present CTL antigens. Such cross-presentation is difficult to achieve by current tumor vaccine strategies. Here, we develop a novel "Retrogen" strategy for DCs to efficiently cross-present an intracellular tumor antigen, MAGE-3, to both MHC class I and MHC class II in a cognate manner. Specifically, the MAGE-3 gene was linked to a leader sequence at its NH2 terminus for secretion and to a cell-binding domain at its COOH terminus for receptor-mediated internalization. DCs transduced with the modified MAGE-3 gene produced and secreted MAGE-3 proteins, which were efficiently taken up by DCs via receptor-mediated internalization and presented as exogenous antigens to class I and class II molecules. Immunization of mice with the transduced DCs expressing the MAGE-3 fusion protein, termed "Retrogen" for its retrograde transport/internalization after secretion, efficiently induced all arms of the adaptive antitumor immune responses. Thus, this retrogen strategy of using a unifying mechanism for DCs to cross-present an intracellular tumor antigen in a cognate manner could be generally used to improve the efficacy of tumor vaccines and immunotherapies.

Induction of vigorous helper and cytotoxic T cell as well as B cell responses by dendritic cells expressing a modified antigen targeting receptor-mediated internalization pathway.

Efficient Ag presentation is essential to induce effective cellular and humoral immune responses. Thus, one central goal of current immunotherapy and vaccine development is to enhance Ag presentation to induce potent and broad immune responses. Here, a novel Ag presentation strategy is developed by transducing dendritic cells (DCs) to produce an Ag for presentation as an exogenous Ag to efficiently induce both humoral and cellular immunity. The principle of this strategy is illustrated by genetically modifying DCs to secrete a model hepatitis B virus Ag fused with a cell-binding domain and to process the fusion Ag as an exogenous Ag after receptor-mediated internalization for MHC class I and II presentation. Vigorous Ag-specific CD4(+) helper and CD8(+) cytotoxic T cell, as well as B cell, responses were induced by the transduced DCs in mouse models. Thus, this novel strategy uses a receptor-mediated internalization process to efficiently induce all arms of the adaptive immunity and may provide a powerful means to develop potent vaccines and immunotherapies.

The Virginia generalist initiative: lessons learned in a statewide consortium.

In response to Virginia's need for an increased supply of generalist physicians, the state's three medical schools--Eastern Virginia Medical School, Virginia Commonwealth University School of Medicine, and the University of Virginia School of Medicine--have formed a partnership with key governmental stakeholders in the Virginia Generalist Initiative funded by The Robert Wood Johnson Foundation's Generalist Physician Initiative. These state-supported medical schools historically have functioned independently, with little cooperative effort. This paper describes the consortium, its activities, its successes, and its unmet objectives, and uses a series of cases in point to illustrate relevant lessons learned. Some of these lessons are that (1) stakeholders must be involved from the beginning of planning to identify mutual goals and establish consortium protocols; (2) all partners must share a philosophical commitment to the consortium's mission, as well as the time and resources needed; (3) an atmosphere that enables risk-taking behavior must be created; (4) stakeholders must be willing to revise goals and sustain an environment conductive to change; and (5) trust is essential and must be vigilantly maintained. The paper concludes that the Virginia Generalist Initiative has dramatically altered the goals, objectives and programs of the three schools and has succeeded in aligning the schools' strategic objectives with the state's priorities.

Moving from policy to practice in curriculum change at the University of Virginia School of Medicine, East Carolina University School of Medicine, and SUNY-Buffalo School of Medicine.

A set of formative evaluation studies from the medical schools of the University of Virginia (UVA), East Carolina University (ECU), and the State University of New York at Buffalo (SUNY-Buffalo) portrays, in qualitative and quantitative terms, evidence of achievements and obstacles to the curricular reform supported by The Robert Wood Johnson Foundation's Generalist Physician Initiative (GPI). In this paper, innovations in the under-graduate curriculum, a specific course, and instructional strategies are examined. Individual interviews of faculty and focus groups with students assessed opinions about curricular change at the University of Virginia. Questionnaires and focus groups provided information about the impact of course changes at East Carolina University. Questionnaires completed by students provided information of the effect of modifying the instructional strategies at SUNY-Buffalo. The obstacles to implementing change at the three schools included breakdowns in the faculty's understanding and support of change, lack of skills required to implement change, and weakness in coordinating and assessing planned change. Although the GPI catalyzed changes in the content and conduct of generalist education at the three schools, many lessons were learned that are applicable to other medical schools.

Molecular pathogenesis of transplacentally induced mouse lung tumors.

Previous studies from this and other laboratories have shown that treatment of pregnant mice with 3-methylcholanthrene (MC) caused lung tumors in the offspring, the incidence of which correlated with fetal inducibility of Cyp1a1. Analysis of paraffin-embedded lung tissue for Ki-ras-2 mutations indicated that 79% of the lesions examined contained point mutations in codons 12 and 13 of the Ki-ras-2 gene locus, the majority of which (84%) were G-->T transversions. The mutational spectrum was dependent on the tumor stage, as both the incidence of mutation and type of mutation produced correlated with malignant progression of the tumor. Mutations occurred in 60% of the hyperplasias, 80% of the adenomas, and 100% of the adenocarcinomas. In the tumors with mutations, GLY12-->CYS12 transversions occurred in 100% of the hyperplasias, 42% of the adenomas, and 14% of the adenocarcinomas. GLY12-->VAL12 transversions were not observed in hyperplasias and occurred in 42% of the adenomas and 57% of the adenocarcinomas. The remaining ASP12 and ARG13 mutations occurred only in adenomas (17%) and adenocarcinomas (29%). The tumors were also analyzed for alterations in the structure or function of the tumor suppressor genes Rb, p53, and Cdkn2a. No mutations were observed in exons 5-8 of the p53 gene. SSCP analysis demonstrated that 2 of 15 lung tumors contained shifted bands at the Cdkn2a gene locus. Sequence analysis had identified these as mutations in exon 2, with a CAC-->TAC transition at base 301 (HIS74-->TYR74) in tumor 23-1 and GGG-->GAG transition at base 350 (GLY90-->GLU90) in tumor 36-1. Northern blot analysis of the larger tumors revealed that 14 of 14 of these large lung tumors exhibited markedly decreased expression of Rb gene transcripts. These results were confirmed by immunohistochemistry. The larger tumors, which exhibited features of adenocarcinomas, showed a marked reduction or almost complete absence of nuclear pRb staining compared with smaller adenomas and normal lung tissue. The results suggest that Ki-ras-2 mutations are an early and frequent event in lung tumorigenesis, and that the type of mutation produced by environmental chemicals can influence the carcinogenic potential of the tumor. The results obtained with the Cdkn2a and Rb genes suggest that alterations in the Rb regulatory axis may play a key role in the pathogenesis of the pulmonary tumors and appear to occur later in the neoplastic process. It appears from these experiments that the combination of mutated Ki-ras-2 and alterations in the Rb regulatory gene locus, which are frequent alterations in human lung tumors, may be the preferred pathway for lung tumor pathogenesis in mice exposed transplacentally to environmental carcinogens.

Predicting pass rates on the American Board of Internal Medicine certifying examination.

Our objective was to determine the ability of the internal medicine In-Training Examination (ITE) to predict pass or fail outcomes on the American Board of Internal Medicine (ABIM) certifying examination and to develop an externally validated predictive model and a simple equation that can be used by residency directors to provide probability feedback for their residency programs. We collected a study sample of 155 internal medicine residents from the three Virginia internal medicine programs and a validation sample of 64 internal medicine residents from a residency program outside Virginia. Scores from both samples were collected across three class cohorts. The Kolmogorov-Smirnov z test indicated no statistically significant difference between the distribution of scores for the two samples (z = 1.284, p = .074). Results of the logistic model yielded a statistically significant prediction of ABIM pass or fail performance from ITE scores (Wald = 35.49, SE = 0.036, df = 1, p < .005) and overall correct classifications for the study sample and validation sample at 79% and 75%, respectively. The ITE is a useful tool in assessing the likelihood of a resident's passing or failing the ABIM certifying examination but is less predictive for residents who received ITE scores between 49 and 66.