When sperm compete to fertilize available ova, selection is expected to favour ejaculate traits that contribute to a male's fertilization success. While there is much evidence to show that selection favours increased numbers of sperm, only a handful of empirical studies have examined how variation in sperm form and function contributes to competitive fertilization success. Here, we examine selection acting on sperm form and function in the externally fertilizing myobatrachid frog, Crinia georgiana. Using in vitro fertilization techniques and controlling for variation in the number of sperm contributed by males in competitive situations, we show that males with a greater proportion of motile sperm, and motile sperm with slower swimming velocities, have an advantage when competing for fertilizations. Sperm morphology and the degree of genetic similarity between putative sires and the female had no influence on competitive fertilization success. These unusual patterns of selection might explain why frog sperm typically exhibit relatively slow swimming speeds and sustained longevity.

Background

Exposure to metal working fluid (MWF) has been associated with outbreaks of extrinsic allergic alveolitis (EAA) in the USA, with bacterial contamination of MWF being a possible cause, but is uncommon in the UK. Twelve workers developed EAA in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. The study had three aims: (1) to measure the extent of the outbreak by identifying other workers who may have developed EAA or other work‐related respiratory diseases; (2) to provide case detection so that those affected could be treated; and (3) to provide epidemiological data to identify the cause of the outbreak.

Methods

The outbreak was investigated in a three‐phase cross‐sectional survey of the workforce. In phase I a respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. In phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481 (94.4%) responded and 48/50 (96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). In phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed.

Results

87 workers (10.4% of the workforce) met case definitions for occupational lung disease, comprising EAA (n = 19), occupational asthma (n = 74) and humidifier fever (n = 7). 12 workers had more than one diagnosis. The peak onset of work‐related breathlessness was Spring 2003. The proportion of workers affected was higher for those using MWF from a large sump (27.3%) than for those working all over the manufacturing area (7.9%) (OR = 4.39, p<0.001). Two workers had positive specific provocation tests to the used but not the unused MWF solution.

Conclusions

Extensive investigation of the outbreak of EAA detected a large number of affected workers, not only with EAA but also occupational asthma. This is the largest reported outbreak in Europe. Mist from used MWF is the likely cause. In workplaces using MWF there is a need to carry out risk assessments, to monitor and maintain fluid quality, to control mist and to carry out respiratory health surveillance.

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked, recessive, lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase. It has multisystemic involvement, with manifestations in the brain, upper respiratory tract, heart, abdomen, joints and bones. Bone involvement leads to decreased growth velocity and short stature in nearly all patients. A therapeutic option for patients with MPS II is enzyme replacement therapy (ERT) with idursulfase (Elaprase®). We compared annual growth rates before and during ERT in 18 patients from Mainz, Germany, and Manchester, UK. Group 1 included nine patients who started ERT before 10 years of age; group 2 contained nine patients aged more than 10 years at the start of ERT. All patients had received weekly or biweekly ERT or placebo for 1 year, followed by ERT for more than 3 years. For patients in group 1, the mean (± SD) height increase was 14.6 ± 5.5 cm during 3 years of ERT. Only one patient in this group (who was below the 3rd percentile when starting ERT) deviated from the normal growth curve over this time. Patients in group 2 had a mean height increase of 8.1 ± 1.7 cm after 3 years of ERT compared with an increase of 1 cm in the year before ERT. ERT seems to have a positive influence on growth in patients with MPS II. Most benefit is seen in patients beginning ERT before the age of 10 years. This supports the recommendation that ERT should be started as early as possible in patients with MPS II.

The increasing availability of personal genomic tests has led to discussions about the validity and utility of such tests and the balance of benefits and harms. A multidisciplinary workshop was convened by the National Institutes of Health and the Centers for Disease Control and Prevention to review the scientific foundation for using personal genomics in risk assessment and disease prevention and to develop recommendations for targeted research. The clinical validity and utility of personal genomics is a moving target with rapidly developing discoveries but little translation research to close the gap between discoveries and health impact. Workshop participants made recommendations in five domains: (1) developing and applying scientific standards for assessing personal genomic tests; (2) developing and applying a multidisciplinary research agenda, including observational studies and clinical trials to fill knowledge gaps in clinical validity and utility; (3) enhancing credible knowledge synthesis and information dissemination to clinicians and consumers; (4) linking scientific findings to evidence-based recommendations for use of personal genomics; and (5) assessing how the concept of personal utility can affect health benefits, costs, and risks by developing appropriate metrics for evaluation. To fulfill the promise of personal genomics, a rigorous multidisciplinary research agenda is needed.

A genetic marker known as apolipoprotein E provides a clear signal of a person’s risk of developing Alzheimer’s disease and thus that person’s future need for long-term care. People who find that they have the variant of the trait that increases Alzheimer’s disease risk are more likely to purchase long-term care insurance after receiving this information. If the information is widely introduced into the insurance market, coverage rates could be affected in different ways, depending on who possesses that information. Policymakers will eventually need to confront the issue of the use of this and other markers in the pricing of long-term care insurance.

This paper explores whether and how the behavioral impact of genotype disclosure can be disentangled from the impact of numerical risk estimates generated by genetic tests. Secondary data analyses are presented from a randomized controlled trial of 162 first-degree relatives of Alzheimer’s disease (AD) patients. Each participant received a lifetime risk estimate of AD. Control group estimates were based on age, gender, family history, and assumed ε4-negative apolipoprotein E (APOE) genotype; intervention group estimates were based upon the first three variables plus true APOE genotype, which was also disclosed. AD-specific self-reported behavior change (diet, exercise, and medication use) was assessed at 12 months. Behavior change was significantly more likely with increasing risk estimates, and also more likely, but not significantly so, in ε4-positive intervention group participants (53% changed behavior) than in control group participants (31%). Intervention group participants receiving ε4-negative genotype feedback (24% changed behavior) and control group participants had similar rates of behavior change and risk estimates, the latter allowing assessment of the independent effects of genotype disclosure. However, collinearity between risk estimates and ε4-positive genotypes, which engender high-risk estimates, prevented assessment of the independent effect of the disclosure of an ε4 genotype. Novel study designs are proposed to determine whether genotype disclosure has an impact upon behavior beyond that of numerical risk estimates.

Purpose

This study evaluates the Alzheimer disease risk perceptions of individuals who accurately recall their genetics-based Alzheimer disease risk assessment.

Methods

Two hundred forty-six unaffected first-degree relatives of patients with Alzheimer disease were enrolled in a multisite randomized controlled trial examining the effects of communicating APOE genotype and lifetime Alzheimer disease risk information.

Results

Among the 158 participants who accurately recalled their Alzheimer disease risk assessment 6 weeks after risk disclosure, 75 (47.5%) believed their Alzheimer disease risk was more than 5% points different from the Alzheimer disease risk estimate they were given. Within this subgroup, 69.3% believed that their Alzheimer disease risk was higher than what they were told (discordant high), whereas 30.7% believed that their Alzheimer disease risk was lower (discordant low). Participants with a higher baseline risk perception were more likely to have a discordant-high risk perception (P < 0.05). Participants in the discordant-low group were more likely to be APOE ε4 positive (P < 0.05) and to score higher on an Alzheimer disease controllability scale (P < 0.05).

Conclusion

Our results indicate that even among individuals who accurately recall their Alzheimer disease risk assessment, many people do not take communicated risk estimates at face value. Further exploration of this clinically relevant response to risk information is warranted.

Perceived risk is a complex concept that influences the genetic counseling process and can affect client coping and behavior. Although the association between family history and risk perception is well recognized in the literature, no studies have explored this relationship specifically in those seeking genetic susceptibility testing for a common chronic condition. REVEAL is a randomized trial assessing the impact of APOE disclosure and genetic risk assessment for Alzheimer’s disease (AD). Using baseline REVEAL data, we hypothesized that there would be a significant association between the degree of AD family history and risk perception of AD, and that this relationship would be stronger in those who believed that genetics is a very important AD risk factor. In our sample of 293 participants, we found that a higher self-perceived risk of AD was associated with strength of family history of AD (p<0.001), belief in genetics as an important AD risk factor (p<0.001), being female (p<0.001) and being Caucasian (p=0.02). These results are the first to demonstrate the association between family history and risk perception in persons volunteering for genetic susceptibility testing for a common complex disease.

Placental hypoxia as a result of impaired trophoblast invasion is suggested to be involved in the pathophysiology of preeclampsia. Hypoxia is a potent stimulus for the release of adenosine, and the actions of adenosine are mediated through four adenosine receptors, A1, A2A, A2B and A3. We investigated the presence, distribution and expression of adenosine receptor subtypes in the human placenta, the expression of the adenosine receptors in placentas from pregnancies complicated by preeclampsia, small for gestational age (SGA) infants and uncomplicated pregnancies, and the effect of hypoxia on placental adenosine receptor expression. Immunofluorescent microscopy localized A1, A2A, A2B and A3 adenosine receptors to the syncytiotrophoblast, endothelial cells and myo-/fibroblasts within the human placenta. Adenosine receptor protein and message expression levels were significantly higher in placentas from preeclamptic pregnancies with or without SGA infants, but not different in pregnancies with SGA infants alone. In vitro exposure of placental villous explants to hypoxia (2% oxygen) increased the expression of A2A adenosine receptor 50%. These data indicate that all four known adenosine receptors are expressed in the human placenta and adenosine receptor expression is significantly higher in pregnancies complicated by preeclampsia. These data are consistent with the hypothesis that differences in placental adenosine receptors may contribute to alterations in placental function in preeclampsia.

Listeria monocytogenes can cause a severe invasive food-borne disease known as listeriosis, and large outbreaks of this disease occur occasionally. Based on molecular-subtype data, epidemic clone (EC) strains have been defined, including ECI and ECIa, which have caused listeriosis outbreaks on different continents. While a number of molecular-subtyping studies of outbreak strains have been reported, few comprehensive data sets of virulence-associated characteristics of these strains are available. We assembled a set of human clinical isolates from 15 outbreaks that occurred worldwide between 1975 and 2002. Initial characterization of these strains showed significant variation in the ability to invade human Caco-2 intestinal epithelial cells and HepG2 hepatic cells; four strains showed consistently reduced invasion in both cell lines. DNA sequencing of inlA, which encodes a protein required for efficient Caco-2 and HepG2 invasion, showed that none of the invasion-attenuated strains contained known virulence-attenuating mutations in inlA. Phylogenetic analyses of inlA sequences revealed a well-supported clade containing a fully invasive ECI strain and three invasion-attenuated ECI strains, along with a fully invasive ECIa strain and an invasion-attenuated ECIa strain. Of the four invasion-attenuated strains, one strain showed both reduced inlA transcript levels and impaired swarming, one strain showed reduced inlA transcript levels, and two strains showed reduced swarming. Overall, our data show that (i) L. monocytogenes strains from outbreaks vary significantly in invasion efficiency and (ii) different mechanisms may contribute to reduced invasion efficiency. Association between EC strains and listeriosis outbreaks may involve characteristics other than virulence phenotypes, including survival and growth in food-associated environments.

Hyperuricemia, a common clinical characteristic of preeclamptic pregnancies, has historically been considered a marker of reduced renal function in preeclamptic women. More recently it has been suggested that uric acid may directly contribute to pathological cell signaling events involved in disease progression as well as maternal and fetal pregnancy outcomes including fetal growth restriction. We hypothesize that the increased frequency of restricted fetal growth seen in relation to increasing uric acid concentrations in preeclamptic women is in part the result of uric acid-induced reductions in amino acid transport across the placenta. The objective of the current study was to examine the effects of uric acid on human placental System A amino acid transport using a primary placental villous explant model. Further, we examined the necessity of uric acid uptake and the role of redox signaling as a potential mechanism through which uric acid may attenuate System A activity. Placental uptake of a radiolabeled amino acid analogue, specific to the System A transporter, was reduced in a concentration-dependent fashion with increasing uric acid (0−7 mg/dL), corresponding to uric acid concentrations measured in healthy pregnant and preeclamptic women in the third trimester. Uric acid-induced reduction in System A activity was partially reversed by NADPH oxidase inhibition and completely eliminated by antioxidant treatment. This study demonstrates inhibition of placental System A amino acid transport with uric acid treatment, as a result of uric acid-induced stimulation of intracellular redox signaling cascades. These findings may be relevant to the increased frequency of fetal growth restriction observed in hyperuricemic preeclampsia. Additionally the results of this study, indicating a detrimental effect of hyperuricemia on amino acid transport in the placenta, at concentrations present in women with preeclampsia, also suggest a role for uric acid in the pathophysiology of preeclampsia.

Background

The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial.

Methods

We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure.

Results

There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P = 0.84), depression (8.8 and 8.7, respectively; P = 0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the non-disclosure group and a disclosure subgroup of subjects carrying the APOE ε4 allele (which is associated with increased risk) also revealed no significant differences. However, the ε4-negative subgroup had a significantly lower level of test-related distress than did the ε4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the ε4-positive and ε4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons).

Conclusions

The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE ε4–negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)

This paper describes the development and psychometric properties of a new scale for assessing the psychological impact of genetic susceptibility testing for Alzheimer’s disease (AD). The new instrument, The REVEAL Impact of Genetic Testing for Alzheimer’s disease (IGT-AD) was designed to examine the unique nature of genetic information and the disease course of AD. The scale was tested as a part of a multicenter clinical trial designed to evaluate the impact of AD risk assessment and data was collected from 276 participants in the study. Using an iterative process of Principal Component Analysis and Cronbach’s alpha, the final 16 item IGT-AD was found to have a two factor structure with excellent internal reliability. Construct validity was established by patterns of correlation with other standardized self-reported measures. This scale should be useful in the identification of patients who maybe susceptible to the negative effects of receiving genetic information, monitoring of patients who have received genetic information, and as a tool for researchers who wish to study the effects of genetic susceptibility testing for AD.

Background

Genetic risk for Alzheimer’s disease (AD) may be conferred by the susceptibility polymorphism apolipoprotein E (APOE), where the ε4 allele increases the risk of developing late-onset Alzheimer’s disease but is not a definitive predictor of the disease, or by autosomal dominant mutations (e.g., the presenilins), which almost inevitably result in early-onset familial Alzheimer’s disease. The purpose of this study was to compare the psychological impact of using these two different types of genetic information to disclose genetic risk for AD to family members of affected patients.

Methods

Data were compared from two separate protocols. The Risk Evaluation and Education for Alzheimer’s Disease (REVEAL) Study is a randomized, multi-site clinical trial that evaluated the impact of susceptibility testing for Alzheimer’s disease with APOE in 101 adult children of Alzheimer’s disease patients. A separate study, conducted at the University of Washington, assessed the impact of deterministic genetic testing by disclosing presenilin-1, presenilin-2, or TAU genotype to 22 individuals at risk for familial Alzheimer’s disease or frontotemporal dementia. In both protocols, participants received genetic counseling and completed the Impact of Event Scale (IES), a measure of test-specific distress. Scores were analyzed at the time point closest to one year post-disclosure at which IES data were available. The role of genetic test result (positive vs. negative) and type of genetic testing (deterministic vs. susceptibility) in predicting log-transformed IES scores was assessed with linear regression, controlling for age, gender, and time from disclosure.

Results

Subjects from the REVEAL Study who learned that they were positive for the susceptibility gene APOE ε4+ experienced similar, low levels of test-specific distress compared to those who received positive results of deterministic testing in the University of Washington study (p= 0.78). APOE ε4+ individuals in the susceptibility protocol experienced more test-specific distress than those who tested ε4− in the same study (p= 0.04); however, among those receiving deterministic test disclosure, the subjects who received positive results did not experience significantly higher levels of distress when compared to those who received negative results (p= 0.88).

Conclusions

The findings of this preliminary study, with limited sample size, suggest that the test-related distress experienced by those receiving positive results for a deterministic mutation is similar to the distress experienced by those receiving positive results from genetic susceptibility testing, and that the majority of participants receiving genotype disclosure do not experience clinically significant distress as indicated by IES scores one year after learning of their test results.

Background

For patients with mild chronic hepatitis C the cost effectiveness of antiviral therapy is unknown.

Aims

To assess whether antiviral therapy (either interferon α or peginterferon α combined with ribavirin) is cost effective at a mild stage compared with waiting and only treating those cases who progress to moderate disease.

Patients

Cases with mild chronic hepatitis C.

Methods

A cost effectiveness model which estimates long term costs and outcomes for patients with mild chronic hepatitis C. The model uses effectiveness and cost data from the UK mild hepatitis C randomised controlled trial, combined with estimates of disease progression and cost from observational studies.

Results

Antiviral treatment at a mild rather than a moderate stage improved outcomes measured by quality adjusted life years (QALYS) gained. The mean cost per QALY gained from antiviral treatment with interferon α‐2b and ribavirin, compared with no treatment at a mild stage, was £4535 ($7108) for patients with genotype non‐1 and £25 188 ($39 480) for patients with genotype 1. Providing peginterferon α‐2b and ribavirin at a mild rather than a moderate stage was also associated with a gain in QALYS; the costs per QALY gained were £7821 ($12 259) for patients with genotype non‐1 and £28 409 ($44 528) for patients with genotype 1.

Conclusions

For patients with chronic hepatitis C, it is generally more cost effective to provide antiviral treatment at a mild rather than a moderate disease stage. For older patients (aged 65 years or over) with genotype 1, antiviral treatment at a mild stage is not cost effective.

Preeclampsia and intrauterine growth restriction (IUGR) are both associated with abnormal remodeling of maternal spiral arteries perfusing the placental site. This would be expected to be associated with reduced fetal growth, yet only one third of infants of mothers with preeclampsia are growth restricted. Infants with IUGR have decreased concentrations of amino acids in their blood and system A amino acid transporter activity is reduced in their placentas. Since infants of preeclamptic pregnancies have increased circulating amino acids, we tested system A amino acid transport activity of placental villous fragments from pregnancies with small for gestational age (SGA) infants with and without maternal preeclampsia and from uncomplicated and preeclamptic pregnancies with normal sized infants. We confirm the reduced uptake of amino acids in SGA pregnancies without preeclampsia but report that placental amino acid uptake of SGA infants with maternal preeclampsia is not reduced and is identical to uptake by normal and preeclamptic pregnancies with normal weight infants.

Background

To address evidence-based effective communication skills in the formal academic half day curriculum of our core internal medicine residency program, we designed and delivered an interactive session using excerpts taken from medically-themed television shows.

Methods

We selected two excerpts from the television show House, and one from Gray's Anatomy and featured them in conjunction with a brief didactic presentation of the Kalamazoo consensus statement on doctor-patient communication. To assess the efficacy of this approach a set of standardized questions were given to our residents once at the beginning and once at the completion of the session.

Results

Our residents indicated that their understanding of an evidence-based model of effective communication such as the Kalamazoo model, and their comfort levels in applying such model in clinical practice increased significantly. Furthermore, residents' understanding levels of the seven essential competencies listed in the Kalamazoo model also improved significantly. Finally, the residents reported that their comfort levels in three challenging clinical scenarios presented to them improved significantly.

Conclusion

We used popular television shows to teach residents in our core internal medicine residency program about effective communication skills with a focus on the Kalamazoo's model. The results of the subjective assessment of this approach indicated that it was successful in accomplishing our objectives.

Aim: To determine the efficacy and safety of perfluorocarbon liquid as a short term postoperative tamponade in patients with retinal detachment from giant retinal tears.

Method: A retrospective consecutive case series of patients with retinal detachment from giant retinal tears who underwent vitrectomy using perfluorocarbon liquid as a short term postoperative internal tamponade. The perfluorocarbon liquid was removed 5–14 days (mean 7.5 days) later and replaced by gas or silicone oil. Scleral buckling was performed in some cases with proliferative vitreoretinopathy. The crystalline lens was removed if there was interference with the surgical view or if it was subluxated. The success rate of retinal reattachment, visual outcome, and postoperative complications were assessed.

Results: A total of 62 eyes of 61 patients with a follow up of 8–69 months (mean 24.5 months) were included. All retinas were attached intraoperatively. 14 eyes (22.6%) developed re-detachment and additional operations were performed in 13 eyes. At final visit, 58 eyes (93.5%) had retinas that remained attached with visual acuity 6/12 or better in 27 eyes (46.5%). The visual acuity improved in 34 eyes (54.8%) with 28 eyes (45.2%) improving at least two Snellen lines, it was unchanged in 20 eyes (32.3%), and was worse in eight eyes (12.9%). Three patients developed glaucoma that was controlled medically. There was no retained perfluorocarbon liquid in any eyes.

Conclusion: Perfluorocarbon liquid appears safe and effective to use as a short term postoperative tamponade in management of retinal detachment from giant retinal tears.

Among older mothers, preeclampsia in the first pregnancy was associated with a reduction in maternal breast cancer risk that was significantly more pronounced in women bearing male than female infants. Androgen concentrations in male, preeclamptic pregnancies were consistent with the hypothesis that elevated pregnancy androgens might mediate this apparent modifying effect of fetal gender.

High levels of pathogenic microorganisms have been documented previously in waters of the Lower Passaic River in northern New Jersey. The purpose of this study was to characterize the microbial contamination of river sediments near combined sewer overflows (CSOs), a known source of pathogens. Concentrations of fecal coliform, total coliform, fecal Streptococcus, fecal Enterococcus, Pseudomonas aeruginosa, Staphylococcus aureus, Giardia lamblia, and Cryptosporidium parvum organisms were measured in 16 samples from three mudflat locations along the Lower Passaic River, as well as from an upstream location. Selected samples were also analyzed for antibiotic resistance. All of the samples contained high concentrations of total coliform, fecal coliform, fecal Streptococcus, and fecal Enterococcus organisms. Analysis of isolates of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli from several samples indicated that each strain was resistant to at least one antibiotic typically used in clinical settings. Eight of 16 samples contained Giardia, and one sample contained Cryptosporidium. With these sampling data, a quantitative microbial risk assessment was conducted to evaluate the probability of infection or illness resulting from incidental ingestion of contaminated sediments over a 1-year period. Three potential exposure scenarios were considered: visitor, recreator, and homeless person. Single-event risk was first evaluated for the three individual exposure scenarios; overall risk was then determined over a 1-year period using Monte Carlo techniques to characterize uncertainty. For fecal Streptococcus and Enterococcus, annualized risk estimates for gastrointestinal illness ranged from approximately 0.42 to 0.53 for recreators, 0.07 to 0.10 for visitors, and 0.62 to 0.72 for homeless individuals across the three sampling locations. Annualized risk of Giardia infection ranged from 0.14 to 0.64 for recreators, 0.01 to 0.1 for visitors, and 0.30 to 0.87 for homeless individuals, across all locations where detected. Cryptosporidium was detected at one location, and the corresponding annualized risk of infection was 0.32, 0.05, and 0.51 for recreators, visitors, and homeless individuals, respectively. This risk assessment suggests that pathogen-contaminated sediments near areas of CSO discharge in the Lower Passaic River could pose a health risk to individuals coming into contact with sediments in the mudflat areas.

Purpose

To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants.

Methods

The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease.

Results

Review of epidemiological data suggested notable differences in risk between African Americans and whites and that Apolipoprotein E genotype predicts risk in both groups. Discussions about the benefits and risks of stratified risk assessments reached consensus that estimates based on data from whites should not preclude enrolling African Americans, but population-specific risk curves should be created if feasible. Risk models specific to ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for the randomized clinical trial that oversampled African Americans.

Conclusion

The Risk Evaluation and Education for Alzheimer Disease study provides an instructive example of a process to develop risk assessment protocols that are sensitive to the implications of genetic testing for multiple ethnic groups with differing levels of risk.

Risk information for Alzheimer disease (AD) may be communicated through susceptibility gene disclosure, even though this is not currently in clinical use. The REVEAL Study is the first randomized clinical trial of risk assessment for AD with apolipoprotein E (APOE) genotype and numerical risk estimate disclosure. We examined whether APOE genotype and numerical risk disclosure to asymptomatic individuals at high risk for AD alters health behaviors. One hundred sixty-two participants were randomized to either intervention (APOE disclosure) or control (no genotype disclosure) groups. Subjects in both groups received numerical lifetime risk estimates of future AD development based on sex and family history of AD. The intervention group received their APOE genotype. Subjects were informed that no proven preventive measures for AD existed and given an information sheet on preventative therapies under investigation. Participants who learned they were ε4 positive were significantly more likely than ε4 negative participants to report AD-specific health behavior change 1 year after disclosure (adjusted odds ratio: 2.73; 95% confidence interval: 1.14, 6.54; P = 0.02). Post hoc analyses revealed similar significant associations between numerical lifetime risk estimates and self-report of AD-specific health behavior change. Despite lack of preventive measures for AD, knowledge of APOE genotype, numerical lifetime risk, or both, influences health behavior.

This article examines four periods of environmental policy-making in the Amazon region of Brazil. It specifically analyses the role of pro-environment and pro-development policy networks in affecting policy design and implementation. It argues that the efforts of environmentalist networks trying to advocate or block relative developmentalist policies in the Amazon depend on three critical factors—whether they are able to attract the support of elites (or at least block their developmentalist policy initiatives); the type and level of international support they have; and the organizational and financial resources that they are able to mobilize. In analysing the four periods, this article finds that while international influences and resources have been substantial in enabling environmentalist networks to flourish and influence the policy, their effectiveness has been nearly always outweighed by Brazilian developmentalist interests. The outcome in each phase has been a different form of stalemate on environmental protection, and the deforestation continued each time, albeit at slower rates. These findings suggest that the key for significantly lower rates of deforestation on the Amazon may be in the ability of pro-environment networks to neutralize opposition by creating an incentive structure that ‘compensates’ potential losers of policies that promote conservation.