A Systems Map of the Challenges of Climate Communication.

Over the past sixty years, scientists have been warning about climate change and its impacts on human health, but evidence suggests that many may not be heeding these concerns. This raises the question of whether new communication approaches are needed to overcome the unique challenges of communicating what people can do to slow or reverse climate change. To better elucidate the challenges of communicating about the links between human activity, climate change and its effects, and identify potential solutions, we developed a systems map of the factors and processes involved based on systems mapping sessions with climate change and communication experts. The systems map revealed 27 communication challenges such as "Limited information on how individual actions contribute to collective human activity," "Limited information on how present activity leads to long-term effects," and "Difficult to represent and communicate complex relationships." The systems map also revealed several themes among the identified challenges that exist in communicating about climate change, including a lack of available data and integrated databases, climate change disciplines working in silos, a need for a lexicon that is easily understood by the public, and the need for new communication strategies to describe processes that take time to manifest.

Feedforward and disinhibitory circuits differentially control activity of cortical somatostatin interneurons during behavioral state transitions.

Interneurons (INs), specifically those in disinhibitory circuits like somatostatin (SST) and vasoactive intestinal peptide (VIP)-INs, are strongly modulated by the behavioral context. Yet, the mechanisms by which these INs are recruited during active states and whether their activity is consistent across sensory cortices remain unclear. We now report that in mice, locomotor activity strongly recruits SST-INs in the primary somatosensory (S1) but not the visual (V1) cortex. This diverse engagement of SST-INs cannot be explained by differences in VIP-IN function but is absent in the presence of visual input, suggesting the involvement of feedforward sensory pathways. Accordingly, inactivating the somatosensory thalamus, but not decreasing VIP-IN activity, significantly reduces the modulation of SST-INs by locomotion. Model simulations suggest that the differences in SST-INs across behavioral states can be explained by varying ratios of VIP- and thalamus-driven activity. By integrating feedforward activity with neuromodulation, SST-INs are anticipated to be crucial for adapting sensory processing to behavioral states.

What is the economic benefit of annual COVID-19 vaccination from the adult individual perspective?

BACKGROUND: With COVID-19 vaccination no longer mandated by many businesses/organizations, it is now up to individuals to decide whether to get any new boosters/updated vaccines going forward. METHODS: We developed a Markov model representing the potential clinical/economic outcomes from an individual perspective in the United States of getting versus not getting an annual COVID-19 vaccine. RESULTS: For an 18-49-year-old, getting vaccinated at its current price ($60) can save the individual on average $30-$603 if the individual is uninsured and $4-$437 if the individual has private insurance, as long as the starting vaccine efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is ≥50% and the weekly risk of getting infected is ≥0.2%, corresponding to an individual interacting with 9 other people in a day under Winter 2023-2024 Omicron SARS-CoV-2 variant conditions with an average infection prevalence of 10%. For a 50-64-year-old, these cost-savings increase to $111-$1,278 and $119-$1,706, for someone without and with insurance, respectively. The risk threshold increases to ≥0.4% (interacting with 19 people/day), when the individual has 13.4% pre-existing protection against infection (e.g., vaccinated 9 months earlier). CONCLUSION: There is both clinical and economic incentive for the individual to continue to get vaccinated against COVID-19 each year.

Health and Economic Value of Eliminating Socioeconomic Disparities in US Youth Physical Activity.

Importance: There are considerable socioeconomic status (SES) disparities in youth physical activity (PA) levels. For example, studies show that lower-SES youth are less active, have lower participation in organized sports and physical education classes, and have more limited access to PA equipment. Objective: To determine the potential public health and economic effects of eliminating disparities in PA levels among US youth SES groups. Design and Setting: An agent-based model representing all 6- to 17-year-old children in the US was used to simulate the epidemiological, clinical, and economic effects of disparities in PA levels among different SES groups and the effect of reducing these disparities. Main Outcomes and Measures: Anthropometric measures (eg, body mass index) and the presence and severity of risk factors associated with weight (stroke, coronary heart disease, type 2 diabetes, or cancer), as well as direct and indirect cost savings. Results: This model, representing all 50 million US children and adolescents 6 to 17 years old, found that if the US eliminates the disparity in youth PA levels across SES groups, absolute overweight and obesity prevalence would decrease by 0.826% (95% CI, 0.821%-0.832%), resulting in approximately 383 000 (95% CI, 368 000-399 000) fewer cases of overweight and obesity and 101 000 (95% CI, 98 000-105 000) fewer cases of weight-related diseases (stroke and coronary heart disease events, type 2 diabetes, or cancer). This would result in more than $15.60 (95% CI, $15.01-$16.10) billion in cost savings over the youth cohort's lifetime. There are meaningful benefits even when reducing the disparity by just 25%, which would result in $1.85 (95% CI, $1.70-$2.00) billion in direct medical costs averted and $2.48 (95% CI, $2.04-$2.92) billion in productivity losses averted. For every 1% in disparity reduction, total productivity losses would decrease by about $83.8 million, and total direct medical costs would decrease by about $68.7 million. Conclusions and Relevance: This study quantified the potential savings from eliminating or reducing PA disparities, which can help policymakers, health care systems, schools, funders, sports organizations, and other businesses better prioritize investments toward addressing these disparities.

How the Timing of Annual COVID-19 Vaccination of Nursing Home Residents and Staff Affects Its Value.

OBJECTIVES: To evaluate the epidemiologic, clinical, and economic value of an annual nursing home (NH) COVID-19 vaccine campaign and the impact of when vaccination starts. DESIGN: Agent-based model representing a typical NH. SETTING AND PARTICIPANTS: NH residents and staff. METHODS: We used the model representing an NH with 100 residents, its staff, their interactions, COVID-19 spread, and its health and economic outcomes to evaluate the epidemiologic, clinical, and economic value of varying schedules of annual COVID-19 vaccine campaigns. RESULTS: Across a range of scenarios with a 60% vaccine efficacy that wanes starting 4 months after protection onset, vaccination was cost saving or cost-effective when initiated in the late summer or early fall. Annual vaccination averted 102 to 105 COVID-19 cases when 30-day vaccination campaigns began between July and October (varying with vaccination start), decreasing to 97 and 85 cases when starting in November and December, respectively. Starting vaccination between July and December saved $3340 to $4363 and $64,375 to $77,548 from the Centers for Medicare & Medicaid Services and societal perspectives, respectively (varying with vaccination start). Vaccination's value did not change when varying the COVID-19 peak between December and February. The ideal vaccine campaign timing was not affected by reducing COVID-19 levels in the community, or varying transmission probability, preexisting immunity, or COVID-19 severity. However, if vaccine efficacy wanes more quickly (over 1 month), earlier vaccination in July resulted in more cases compared with vaccinating later in October. CONCLUSIONS AND IMPLICATIONS: Annual vaccination of NH staff and residents averted the most cases when initiated in the late summer through early fall, at least 2 months before the COVID-19 winter peak but remained cost saving or cost-effective when it starts in the same month as the peak. This supports tethering COVID vaccination to seasonal influenza campaigns (typically in September-October) for providing protection against SARS-CoV-2 winter surges in NHs.

The potential epidemiologic, clinical, and economic value of a universal coronavirus vaccine: a modelling study.

Background: With efforts underway to develop a universal coronavirus vaccine, otherwise known as a pan-coronavirus vaccine, this is the time to offer potential funders, researchers, and manufacturers guidance on the potential value of such a vaccine and how this value may change with differing vaccine and vaccination characteristics. Methods: Using a computational model representing the United States (U.S.) population, the spread of SARS-CoV-2 and the various clinical and economic outcomes of COVID-19 such as hospitalisations, deaths, quality-adjusted life years (QALYs) lost, productivity losses, direct medical costs, and total societal costs, we explored the impact of a universal vaccine under different circumstances. We developed and populated this model using data reported by the CDC as well as observational studies conducted during the COVID-19 pandemic. Findings: A pan-coronavirus vaccine would be cost saving in the U.S. as a standalone intervention as long as its vaccine efficacy is ≥10% and vaccination coverage is ≥10%. Every 1% increase in efficacy between 10% and 50% could avert an additional 395,000 infections and save $1.0 billion in total societal costs ($45.3 million in productivity losses, $1.1 billion in direct medical costs). It would remain cost saving even when a strain-specific coronavirus vaccine would be subsequently available, as long as it takes at least 2-3 months to develop, test, and bring that more specific vaccine to the market. Interpretation: Our results provide support for the development and stockpiling of a pan-coronavirus vaccine and help delineate the vaccine characteristics to aim for in development of such a vaccine. Funding: The National Science Foundation, the Agency for Healthcare Research and Quality, the National Institute of General Medical Sciences, the National Center for Advancing Translational Sciences, and the City University of New York.

Benefits of Meeting the Healthy People 2030 Youth Sports Participation Target.

INTRODUCTION: Healthy People 2030, a U.S. government health initiative, has indicated that increasing youth sports participation to 63.3% is a priority in the U.S. This study quantified the health and economic value of achieving this target. METHODS: An agent-based model developed in 2023 represents each person aged 6-17 years in the U.S. On each simulated day, agents can participate in sports that affect their metabolic and mental health in the model. Each agent can develop different physical and mental health outcomes, associated with direct and indirect costs. RESULTS: Increasing the proportion of youth participating in sports from the most recent participation levels (50.7%) to the Healthy People 2030 target (63.3%) could reduce overweight/obesity prevalence by 3.37% (95% CI=3.35%, 3.39%), resulting in 1.71 million fewer cases of overweight/obesity (95% CI=1.64, 1.77 million). This could avert 352,000 (95% CI=336,200, 367,500) cases of weight-related diseases and gain 1.86 million (95% CI=1.86, 1.87 million) quality-adjusted life years, saving $22.55 billion (95% CI=$22.46, $22.63 billion) in direct medical costs and $25.43 billion (95% CI= $25.25, $25.61 billion) in productivity losses. This would also reduce depression/anxiety symptoms, saving $3.61 billion (95% CI=$3.58, $3.63 billion) in direct medical costs and $28.38 billion (95% CI=$28.20, $28.56 billion) in productivity losses. CONCLUSIONS: This study shows that achieving the Healthy People 2030 objective could save third-party payers, businesses, and society billions of dollars for each cohort of persons aged 6-17 years, savings that would continue to repeat with each new cohort. This suggests that even if a substantial amount is invested toward this objective, such investments could pay for themselves.

Cost-effectiveness of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing and isolation strategies in nursing homes.

OBJECTIVE: Nursing home residents may be particularly vulnerable to coronavirus disease 2019 (COVID-19). Therefore, a question is when and how often nursing homes should test staff for COVID-19 and how this may change as severe acute respiratory coronavirus virus 2 (SARS-CoV-2) evolves. DESIGN: We developed an agent-based model representing a typical nursing home, COVID-19 spread, and its health and economic outcomes to determine the clinical and economic value of various screening and isolation strategies and how it may change under various circumstances. RESULTS: Under winter 2023-2024 SARS-CoV-2 omicron variant conditions, symptom-based antigen testing averted 4.5 COVID-19 cases compared to no testing, saving $191 in direct medical costs. Testing implementation costs far outweighed these savings, resulting in net costs of $990 from the Centers for Medicare & Medicaid Services perspective, $1,545 from the third-party payer perspective, and $57,155 from the societal perspective. Testing did not return sufficient positive health effects to make it cost-effective [$50,000 per quality-adjusted life-year (QALY) threshold], but it exceeded this threshold in ≥59% of simulation trials. Testing remained cost-ineffective when routinely testing staff and varying face mask compliance, vaccine efficacy, and booster coverage. However, all antigen testing strategies became cost-effective (≤$31,906 per QALY) or cost saving (saving ≤$18,372) when the severe outcome risk was ≥3 times higher than that of current omicron variants. CONCLUSIONS: SARS-CoV-2 testing costs outweighed benefits under winter 2023-2024 conditions; however, testing became cost-effective with increasingly severe clinical outcomes. Cost-effectiveness can change as the epidemic evolves because it depends on clinical severity and other intervention use. Thus, nursing home administrators and policy makers should monitor and evaluate viral virulence and other interventions over time.

The Need for Systems Approaches for Precision Communications in Public Health.

A major challenge in communicating health-related information is the involvement of multiple complex systems from the creation of the information to the sources and channels of dispersion to the information users themselves. To date, public health communications approaches have often not adequately accounted for the complexities of these systems to the degree necessary to have maximum impact. The virality of COVID-19 misinformation and disinformation has brought to light the need to consider these system complexities more extensively. Unaided, it is difficult for humans to see and fully understand complex systems. Luckily, there are a range of systems approaches and methods, such as systems mapping and systems modeling, that can help better elucidate complex systems. Using these methods to better characterize the various systems involved in communicating public health-related information can lead to the development of more tailored, precise, and proactive communications. Proceeding in an iterative manner to help design, implement, and adjust such communications strategies can increase impact and leave less opportunity for misinformation and disinformation to spread.

Research gaps and opportunities in precision nutrition: an NIH workshop report.

Precision nutrition is an emerging concept that aims to develop nutrition recommendations tailored to different people's circumstances and biological characteristics. Responses to dietary change and the resulting health outcomes from consuming different diets may vary significantly between people based on interactions between their genetic backgrounds, physiology, microbiome, underlying health status, behaviors, social influences, and environmental exposures. On 11-12 January 2021, the National Institutes of Health convened a workshop entitled "Precision Nutrition: Research Gaps and Opportunities" to bring together experts to discuss the issues involved in better understanding and addressing precision nutrition. The workshop proceeded in 3 parts: part I covered many aspects of genetics and physiology that mediate the links between nutrient intake and health conditions such as cardiovascular disease, Alzheimer disease, and cancer; part II reviewed potential contributors to interindividual variability in dietary exposures and responses such as baseline nutritional status, circadian rhythm/sleep, environmental exposures, sensory properties of food, stress, inflammation, and the social determinants of health; part III presented the need for systems approaches, with new methods and technologies that can facilitate the study and implementation of precision nutrition, and workforce development needed to create a new generation of researchers. The workshop concluded that much research will be needed before more precise nutrition recommendations can be achieved. This includes better understanding and accounting for variables such as age, sex, ethnicity, medical history, genetics, and social and environmental factors. The advent of new methods and technologies and the availability of considerably more data bring tremendous opportunity. However, the field must proceed with appropriate levels of caution and make sure the factors listed above are all considered, and systems approaches and methods are incorporated. It will be important to develop and train an expanded workforce with the goal of reducing health disparities and improving precision nutritional advice for all Americans.

The Impact of a Place-Tailored Digital Health App Promoting Exercise Classes on African American Women's Physical Activity and Obesity: Simulation Study.

BACKGROUND: The increasing prevalence of smartphone apps to help people find different services raises the question of whether apps to help people find physical activity (PA) locations would help better prevent and control having overweight or obesity. OBJECTIVE: The aim of this paper is to determine and quantify the potential impact of a digital health intervention for African American women prior to allocating financial resources toward implementation. METHODS: We developed our Virtual Population Obesity Prevention, agent-based model of Washington, DC, to simulate the impact of a place-tailored digital health app that provides information about free recreation center classes on PA, BMI, and overweight and obesity prevalence among African American women. RESULTS: When the app is introduced at the beginning of the simulation, with app engagement at 25% (eg, 25% [41,839/167,356] of women aware of the app; 25% [10,460/41,839] of those aware downloading the app; and 25% [2615/10,460] of those who download it receiving regular push notifications), and a 25% (25/100) baseline probability to exercise (eg, without the app), there are no statistically significant increases in PA levels or decreases in BMI or obesity prevalence over 5 years across the population. When 50% (83,678/167,356) of women are aware of the app; 58.23% (48,725/83,678) of those who are aware download it; and 55% (26,799/48,725) of those who download it receive regular push notifications, in line with existing studies on app usage, introducing the app on average increases PA and decreases weight or obesity prevalence, though the changes are not statistically significant. When app engagement increased to 75% (125,517/167,356) of women who were aware, 75% (94,138/125,517) of those who were aware downloading it, and 75% (70,603/94,138) of those who downloaded it opting into the app's push notifications, there were statistically significant changes in PA participation, minutes of PA and obesity prevalence. CONCLUSIONS: Our study shows that a digital health app that helps identify recreation center classes does not result in substantive population-wide health effects at lower levels of app engagement. For the app to result in statistically significant increases in PA and reductions in obesity prevalence over 5 years, there needs to be at least 75% (125,517/167,356) of women aware of the app, 75% (94,138/125,517) of those aware of the app download it, and 75% (70,603/94,138) of those who download it opt into push notifications. Nevertheless, the app cannot fully overcome lack of access to recreation centers; therefore, public health administrators as well as parks and recreation agencies might consider incorporating this type of technology into multilevel interventions that also target the built environment and other social determinants of health.

A Retrospective Comparison of Patient and Pressure Injury Data at Two Time Points in a Regional Hospital in France.

BACKGROUND: Pressure injuries (PIs) are a significant problem for health care institutions. PURPOSE: A retrospective study of patient data was conducted at a semi-urban state hospital in France, aiming to evaluate the rate of PIs and variables that may influence PI prevalence and care at 2 different time points. METHODS: Patient demographic, clinical, PI and PI prevention, and care variables were retrieved from the charts of all patients on all wards (except pediatrics and obstetrics) on October 20, 2009, and on October 24, 2013-4 years apart. Qualitative data were compared between the 2 dates using a t-test for independent variables. The remaining variables were compared using Pearson's chi-square method. P < .05 was considered significant. RESULTS: No significant differences were noted in PI rates (19% for 2009 and 16% for 2013) or the timing of their occurrence (51% occurred following admission in 2009, and 58.3% occurred after admission in 2013). Significant differences were found with regard to patient age (average, 73.97 and 76.22 years old in 2009 and 2013, respectively; P = .014) and rates of serious injuries (27% and 43% were stages 3 and 4 in 2009 and 2013, respectively; P = .010). Compared with 2009, in 2013, significantly more patients were placed on a specialty mattress and provided nutritional supplements and fewer were provided percutaneous endoscopic gastrostomy or nasogastric tubes. CONCLUSION: The rate of PIs was not different between these 2 time points despite improvements in the use of preventive and therapeutic measures, perhaps due to the increased age and frailty of the patient population in 2013 compared with 2009. Additional prospective research across multiple health care entities is warranted.

Sleep apnoea and endothelial dysfunction: An individual patient data meta-analysis.

We performed an individual patient data meta-analysis to investigate the association between obstructive sleep apnoea (OSA) severity and the reactive hyperaemia index (RHI) measured by peripheral arterial tonometry (PAT), a validated measurement of endothelial function, and a strong predictor of late cardiovascular (CV) events. Patients from 12 studies underwent PAT and overnight polysomnography or respiratory polygraphy for suspected OSA. Endothelial dysfunction was defined by a log-transformed RHI<0.51. Subgroup analyses were performed to investigate this relationship in specific populations. Among 730 patients without overt CV disease, 387 (53.0%) had severe OSA (apnoea-hypopnea index ≥30) and 164 (22.5%) exhibited endothelial dysfunction. After adjustment for age, gender, diastolic blood pressure, obesity, diabetes and chronic obstructive pulmonary disease, endothelial dysfunction was associated with severe OSA (odds ratio, OR [95% confidence interval]: 2.27 [1.12-4.60]; p = 0.02), and nocturnal hypoxemia defined by >20 min with oxygen saturation <90% (OR: 1.83 [1.22-2.92]; p = 0.004) or mean oxygen saturation <92% (OR: 1.52 [1.17-1.96]; p = 0.002). On subgroup analyses, the association between severe OSA and endothelial dysfunction was not significant in patients with hypertension, obesity and/or diabetes. Among adults without overt CV disease, severe OSA is independently associated with an increased risk of endothelial dysfunction that may predispose to late CV events.

Long-term effects of cochlear implantation on the intelligibility of speech in French-speaking children.

Our study compares the intelligibility of French-speaking children with a cochlear implant (N = 13) and age-matched children with typical hearing (N = 13) in a narrative task. This contrasts with previous studies in which speech intelligibility of children with cochlear implants is most often tested using repetition or reading tasks. Languages other than English are seldom considered. Their productions were graded by naive and expert listeners. The results show that (1) children with CIs have lower intelligibility, (2) early implantation is a predictor of good intelligibility, and (3) late implantation after two years of age does not prevent the children from eventually reaching good intelligibility.

Statistical Methodology for the Analysis of Repeated Duration Data in Behavioral Studies.

Purpose: Repeated duration data are frequently used in behavioral studies. Classical linear or log-linear mixed models are often inadequate to analyze such data, because they usually consist of nonnegative and skew-distributed variables. Therefore, we recommend use of a statistical methodology specific to duration data. Method: We propose a methodology based on Cox mixed models and written under the R language. This semiparametric model is indeed flexible enough to fit duration data. To compare log-linear and Cox mixed models in terms of goodness-of-fit on real data sets, we also provide a procedure based on simulations and quantile-quantile plots. Results: We present two examples from a data set of speech and gesture interactions, which illustrate the limitations of linear and log-linear mixed models, as compared to Cox models. The linear models are not validated on our data, whereas Cox models are. Moreover, in the second example, the Cox model exhibits a significant effect that the linear model does not. Conclusions: We provide methods to select the best-fitting models for repeated duration data and to compare statistical methodologies. In this study, we show that Cox models are best suited to the analysis of our data set.

Pandemic (H1N1) 2009 in captive cheetah.

We describe virus isolation, full genome sequence analysis, and clinical pathology in ferrets experimentally inoculated with pandemic (H1N1) 2009 virus recovered from a clinically ill captive cheetah that had minimal human contact. Evidence of reverse zoonotic transmission by fomites underscores the substantial animal and human health implications of this virus.

Industrial yeast strain engineered to ferment ethanol from lignocellulosic biomass.

In this study an industrial Saccharomyces cerevisiae yeast strain capable of fermenting ethanol from pretreated lignocellulosic material was engineered. Genes encoding cellulases (endoglucanase, exoglucanase and ß-glucosidase) were integrated into the chromosomal ribosomal DNA and delta regions of a derivative of the K1-V1116 wine yeast strain. The engineered cellulolytic yeast produces ethanol in one step through simultaneous saccharification and fermentation of pretreated biomass without the addition of exogenously produced enzymes. When ethanol fermentation was performed with 10% dry weight of pretreated corn stover, the recombinant strain fermented 63% of the cellulose in 96 h and the ethanol titer reached 2.6% v/v. These results demonstrate that cellulolytic S. cerevisiae strains can be used as a platform for developing an economical advanced biofuel process.

Methodological approach for substantiating disease freedom in a heterogeneous small population. Application to ovine scrapie, a disease with a strong genetic susceptibility.

Demonstrating disease freedom is becoming important in different fields including animal disease control. Most methods consider sampling only from a homogeneous population in which each animal has the same probability of becoming infected. In this paper, we propose a new methodology to calculate the probability of detecting the disease if it is present in a heterogeneous population of small size with potentially different risk groups, differences in risk being defined using relative risks. To calculate this probability, for each possible arrangement of the infected animals in the different groups, the probability that all the animals tested are test-negative given this arrangement is multiplied by the probability that this arrangement occurs. The probability formula is developed using the assumption of a perfect test and hypergeometric sampling for finite small size populations. The methodology is applied to scrapie, a disease affecting small ruminants and characterized in sheep by a strong genetic susceptibility defining different risk groups. It illustrates that the genotypes of the tested animals influence heavily the confidence level of detecting scrapie. The results present the statistical power for substantiating disease freedom in a small heterogeneous population as a function of the design prevalence, the structure of the sample tested, the structure of the herd and the associated relative risks.

Comparison of strategies for substantiating freedom from scrapie in a sheep flock.

BACKGROUND: The public health threat represented by a potential circulation of bovine spongiform encephalopathy agent in sheep population has led European animal health authorities to launch large screening and genetic selection programmes. If demonstrated, such a circulation would have dramatic economic consequences for sheep breeding sector. In this context, it is important to evaluate the feasibility of qualification procedures that would allow sheep breeders demonstrating their flock is free from scrapie. Classical approaches, based on surveys designed to detect disease presence, do not account for scrapie specificities: the genetic variations of susceptibility and the absence of live diagnostic test routinely available. Adapting these approaches leads to a paradoxical situation in which a greater amount of testing is needed to substantiate disease freedom in genetically resistant flocks than in susceptible flocks, whereas probability of disease freedom is a priori higher in the former than in the latter. The goal of this study was to propose, evaluate and compare several qualification strategies for demonstrating a flock is free from scrapie. RESULTS: A probabilistic framework was defined that accounts for scrapie specificities and allows solving the preceding paradox. Six qualification strategies were defined that combine genotyping data, diagnostic tests results and flock pedigree. These were compared in two types of simulated flocks: resistant and susceptible flocks. Two strategies allowed demonstrating disease freedom in several years, for the majority of simulated flocks: a strategy in which all the flock animals are genotyped, and a strategy in which only founders animals are genotyped, the flock pedigree being known. In both cases, diagnostic tests are performed on culled animals. The less costly strategy varied according to the genetic context (resistant or susceptible) and to the relative costs of a genotyping exam and of a diagnostic test. CONCLUSION: This work demonstrates that combining data sources allows substantiating a flock is free from scrapie within a reasonable time frame. Qualification schemes could thus be a useful tool for voluntary or mandatory scrapie control programmes. However, there is no general strategy that would always minimize the costs and choice of the strategy should be adapted to local genetic conditions.

Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: a case series with 15-year follow-up.

BACKGROUND: Aristolochic acids are nephrotoxins and predispose to upper-tract urothelial carcinoma. The risk of bladder urothelial carcinoma after kidney transplantation and its relationship to upper-tract urothelial carcinoma is not well defined. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Single-center cohort of 38 women given kidney transplants for end-stage aristolochic acid nephropathy. OUTCOMES & MEASUREMENTS: The prevalence of upper urinary tract urothelial carcinoma was determined by collecting pathological results of specimens obtained by means of bilateral ureteronephrectomy. We also established the cumulative incidence of bladder urothelial carcinoma in biopsies performed during prospective screening cystoscopies during a 15-year follow-up. RESULTS: Upper-tract urothelial carcinoma was found in 17 patients with aristolochic acid nephropathy (44.7%). During follow-up, bladder urothelial carcinoma was diagnosed in 15 patients 68 to 169 months after cessation of aristolochic acid exposure (39.5%): 8 urothelial carcinoma in situ, 4 noninvasive low-grade papillary urothelial carcinoma, and 3 infiltrating urothelial carcinoma. 12 of 17 patients (71%) with a history of upper-tract urothelial carcinoma developed bladder urothelial carcinoma during follow-up, whereas this occurred in only 3 of 21 patients (14%) without upper-tract urothelial carcinoma (P < 0.01). Despite local and/or systemic chemotherapy, 3 patients died and 2 radical cystectomies were performed. LIMITATIONS: Small sample size of this case series. CONCLUSIONS: Upper-tract and bladder urothelial carcinoma are dramatic complications in kidney transplant recipients with aristolochic acid nephropathy, confirming the carcinogenic properties of aristolochic acids. We identified upper-tract urothelial carcinoma as a potent risk factor for the subsequent development of bladder urothelial carcinoma after kidney transplantation for aristolochic acid nephropathy. Because this complication may occur years after aristolochic acid discontinuation, we suggest regular cystoscopies in addition to the bilateral ureteronephrectomy in kidney transplant recipients with aristolochic acid nephropathy.