Wind Loads on Dynamic Message Cabinets and Behavior of Supporting Trusses, TR-612, 2013

Large Dynamic Message Signs (DMSs) have been increasingly used on freeways, expressways and major arterials to better manage the traffic flow by providing accurate and timely information to drivers. Overhead truss structures are typically employed to support those DMSs allowing them to provide wider display to more lanes. In recent years, there is increasing evidence that the truss structures supporting these large and heavy signs are subjected to much more complex loadings than are typically accounted for in the codified design procedures. Consequently, some of these structures have required frequent inspections, retrofitting, and even premature replacement. Two manufacturing processes are primarily utilized on truss structures - welding and bolting. Recently, cracks at welding toes were reported for the structures employed in some states. Extremely large loads (e.g., due to high winds) could cause brittle fractures, and cyclic vibration (e.g., due to diurnal variation in temperature or due to oscillations in the wind force induced by vortex shedding behind the DMS) may lead to fatigue damage, as these are two major failures for the metallic material. Wind and strain resulting from temperature changes are the main loads that affect the structures during their lifetime. The American Association of State Highway and Transportation Officials (AASHTO) Specification defines the limit loads in dead load, wind load, ice load, and fatigue design for natural wind gust and truck-induced gust. The objectives of this study are to investigate wind and thermal effects in the bridge type overhead DMS truss structures and improve the current design specifications (e.g., for thermal design). In order to accomplish the objective, it is necessary to study structural behavior and detailed strain-stress of the truss structures caused by wind load on the DMS cabinet and thermal load on the truss supporting the DMS cabinet. The study is divided into two parts. The Computational Fluid Dynamics (CFD) component and part of the structural analysis component of the study were conducted at the University of Iowa while the field study and related structural analysis computations were conducted at the Iowa State University. The CFD simulations were used to determine the air-induced forces (wind loads) on the DMS cabinets and the finite element analysis was used to determine the response of the supporting trusses to these pressure forces. The field observation portion consisted of short-term monitoring of several DMS Cabinet/Trusses and long-term monitoring of one DMS Cabinet/Truss. The short-term monitoring was a single (or two) day event in which several message sign panel/trusses were tested. The long-term monitoring field study extended over several months. Analysis of the data focused on trying to identify important behaviors under both ambient and truck induced winds and the effect of daily temperature changes. Results of the CFD investigation, field experiments and structural analysis of the wind induced forces on the DMS cabinets and their effect on the supporting trusses showed that the passage of trucks cannot be responsible for the problems observed to develop at trusses supporting DMS cabinets. Rather the data pointed toward the important effect of the thermal load induced by cyclic (diurnal) variations of the temperature. Thermal influence is not discussed in the specification, either in limit load or fatigue design. Although the frequency of the thermal load is low, results showed that when temperature range is large the restress range would be significant to the structure, especially near welding areas where stress concentrations may occur. Moreover stress amplitude and range are the primary parameters for brittle fracture and fatigue life estimation. Long-term field monitoring of one of the overhead truss structures in Iowa was used as the research baseline to estimate the effects of diurnal temperature changes to fatigue damage. The evaluation of the collected data is an important approach for understanding the structural behavior and for the advancement of future code provisions. Finite element modeling was developed to estimate the strain and stress magnitudes, which were compared with the field monitoring data. Fatigue life of the truss structures was also estimated based on AASHTO specifications and the numerical modeling. The main conclusion of the study is that thermal induced fatigue damage of the truss structures supporting DMS cabinets is likely a significant contributing cause for the cracks observed to develop at such structures. Other probable causes for fatigue damage not investigated in this study are the cyclic oscillations of the total wind load associated with the vortex shedding behind the DMS cabinet at high wind conditions and fabrication tolerances and induced stresses due to fitting of tube to tube connections.

The definition of quality of life in solid organ transplantation: A psychological qualitative model

Quality of life has been extensively discussed in acute and chronic illnesses. However a dynamic model grounded in the experience of patients in the course of transplantation has not been to our knowledge developed. In a qualitative longitudinal study, patients awaiting solid organ transplantation participated in semi-structured interviews: Exploring topics pre-selected on previous research literature review. Creative interview was privileged, open to themes patients would like to discuss at the different steps of the transplantation process. A qualitative thematic and reflexive analysis was performed, and a model of the dimensions constitutive of quality of life from the perspective of the patients was elaborated. Quality of life is not a stable construct in a long lasting illness-course, but evolves with illness constraints, treatments and outcomes. Dimensions constitutive of quality of life are defined, each of them containing different sub-categories depending on the organ related illness co-morbidities and the stage of illness-course.

Dietary resveratrol prevents alzheimer's markers and increases life span in SAMP8

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study.

Background We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. Patients and methods From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. Results Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. Conclusions Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.

Male mutation bias and possible long-term effects of human activities.

The ability of a population to adapt to changing environments depends critically on the amount and kind of genetic variability it possesses. Mutations are an important source of new genetic variability and may lead to new adaptations, especially if the population size is large. Mutation rates are extremely variable between and within species, and males usually have higher mutation rates as a result of elevated rates of male germ cell division. This male bias affects the overall mutation rate. We examined the factors that influence male mutation bias, and focused on the effects of classical life-history parameters, such as the average age at reproduction and elevated rates of sperm production in response to sexual selection and sperm competition. We argue that human-induced changes in age at reproduction or in sexual selection will affect male mutation biases and hence overall mutation rates. Depending on the effective population size, these changes are likely to influence the long-term persistence of a population.

Melanin-specific life-history strategies.

Abstract The maintenance of genetic variation is a long-standing issue because the adaptive value of life-history strategies associated with each genetic variant is usually unknown. However, evidence for the coexistence of alternative evolutionary fixed strategies at the population level remains scarce. Because in the tawny owl (Strix aluco) heritable melanin-based coloration shows different physiological and behavioral norms of reaction, we investigated whether coloration is associated with investment in maintenance and reproduction. Light melanic owls had lower adult survival compared to dark melanic conspecifics, and color variation was related to the trade-off between offspring number and quality. When we experimentally enlarged brood size, light melanic males produced more fledglings but in poorer condition, and they were less often recruited in the local breeding population than those of darker melanic conspecifics. Our results also suggest that dark melanic males allocate a constant effort to raise their brood independently of environmental conditions, whereas lighter melanic males finely adjust reproductive effort in relation to changes in environmental conditions. Color traits can therefore be associated with life-history strategies, and stochastic environmental perturbation can temporarily favor one phenotype over others. The existence of fixed strategies implies that some phenotypes can sometimes display a "maladapted" strategy. Long-term population monitoring is therefore vital for a full understanding of how different genotypes deal with trade-offs.

Life designing: A paradigm for career construction in the 21st century

At the beginning of the 21st century, a new social arrangement of work poses a series of questions and challenges to scholars who aim to help people develop their working lives. Given the globalization of career counseling, we decided to address these issues and then to formulate potentially innovative responses in an international forum. We used this approach to avoid the difficulties of creating models and methods in one country and then trying to export them to other countries where they would be adapted for use. This article presents the initial outcome of this collaboration, a counseling model and methods. The life-designing model for career intervention endorses five presuppositions about people and their work lives: contextual possibilities, dynamic processes, non-linear progression, multiple perspectives, and personal patterns. Thinking from these five presuppositions, we have crafted a contextualized model based on the epistemology of social constructionism, particularly recognizing that an individual's knowledge and identity are the product of social interaction and that meaning is co-constructed through discourse. The life-design framework for counseling implements the theories of self-constructing [Guichard, J. (2005). Life-long self-construction. International Journal for Educational and Vocational Guidance, 5, 111-124] and career construction [Savickas, M. L. (2005). The theory and practice of career construction. In S. D. Brown & R. W. Lent (Eds.), Career development and counselling: putting theory and research to work (pp. 42-70). Hoboken, NJ: Wiley] that describe vocational behavior and its development. Thus, the framework is structured to be life-long, holistic, contextual, and preventive.

Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer

Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24,and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 16 months after treatment, with larger declines following surgery in urinary and sexual QOL as compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to surgery. Long-term urinary and sexual QOL declines remained clinically significantly lower for surgery patients but not for SBRT patients. Conclusions: Overall, these results may have implications for patient and physician clinical decision making which are often influenced by QOL. These differences in sexual, urinary and bowel QOL should be closely considered in selecting the right treatment, especially in evaluating the value of non-invasive treatments, such as SBRT.

A Continuous Span Aluminum Girder Concrete Deck Bridge - Part 2 of 2: Fatigue Tests of Aluminum Girders, Final Report, 1997

In 1957, the Iowa State Highway Commission, with financial assistance from the aluminum industry, constructed a 220-ft (67-m) long, four-span continuous, aluminum girder bridge to carry traffic on Clive Road (86th Street) over Interstate 80 near Des Moines, Iowa. The bridge had four, welded I-shape girders that were fabricated in pairs with welded diaphragms between an exterior and an interior girder. The interior diaphragms between the girder pairs were bolted to girder brackets. A composite, reinforced concrete deck served as the roadway surface. The bridge, which had performed successfully for about 35 years of service, was removed in the fall of 1993 to make way for an interchange at the same location. Prior to the bridge demolition, load tests were conducted to monitor girder and diaphragm bending strains and deflections in the northern end span. Fatigue testing of the aluminum girders that were removed from the end spans were conducted by applying constant-amplitude, cyclic loads. These tests established the fatigue strength of an existing, welded, flange-splice detail and added, welded, flange-cover plates and horizontal web plate attachment details. This part, Part 2, of the final report focuses on the fatigue tests of the aluminum girder sections that were removed from the bridge and on the analysis of the experimental data to establish the fatigue strength of full-size specimens. Seventeen fatigue fractures that were classified as Category E weld details developed in the seven girder test specimens. Linear regression analyses of the fatigue test results established both nominal and experimental stress-range versus load cycle relationships (SN curves) for the fatigue strength of fillet-welded connections. The nominal strength SN curve obtained by this research essentially matched the SN curve for Category E aluminum weldments given in the AASHTO LRFD specifications. All of the Category E fatigue fractures that developed in the girder test specimens satisfied the allowable SN relationship specified by the fatigue provisions of the Aluminum Association. The lower-bound strength line that was set at two standard deviations below the least squares regression line through the fatigue fracture data points related well with the Aluminum Association SN curve. The results from the experimental tests of this research have provided additional information regarding behavioral characteristics of full-size, aluminum members and have confirmed that aluminum has the strength properties needed for highway bridge girders.

Neurocognitive deficits and personality traits among euthymic patients with mood disorders in late life.

BACKGROUND: Previous studies revealed that acute depressive episodes are associated with both cognitive deficits and modified personality patterns in late life. Whether or not these psychological changes are present after remission remains a matter of debate. To date, no study provided concomitant assessment of cognition and psychological functions in this particular clinical setting. METHOD: Using a cross-sectional design, 58 remitted outpatients (36 with unipolar early-onset depression (EOD) and 22 with bipolar disorder (BD)) were compared to 62 healthy controls. Assessment included detailed neurocognitive measures and evaluation of the five factor personality dimensions (NEO-Personality Inventory). RESULTS: Group comparisons revealed significant slower processing speed, working and episodic memory performances in BD patients. EOD patients showed cognitive abilities comparable to those of elderly controls. In NEO PI assessment, both BD and EOD patients displayed higher Depressiveness facet scores. In addition, the EOD but not BD group had lower Extraversion factor, and Warmth and Positive Emotion facet scores than controls. CONCLUSIONS: After remission from acute affective symptoms, older BD patients show significant impairment in several cognitive functions while neuropsychological performances remained intact in elderly patients with EOD. Supporting a long-lasting psychological vulnerability, EOD patients are more prone to develop emotion-related personality trait changes than BD patients.

A systematic review of existing data on long-term lithium therapy: neuroprotective or neurotoxic?

Lithium is an efficacious agent for the treatment of bipolar disorder, but it is unclear to what extent its long-term use may result in neuroprotective or toxic consequences. Medline was searched with the combination of the word 'Lithium' plus key words that referred to every possible effect on the central nervous system. The papers were further classified into those supporting a neuroprotective effect, those in favour of a neurotoxic effect and those that were neutral. The papers were classified into research in humans, animal and in-vitro research, case reports, and review/opinion articles. Finally, the Natural Standard evidence-based validated grading rationale was used to validate the data. The Medline search returned 970 papers up to February 2006. Inspection of the abstracts supplied 214 papers for further reviewing. Eighty-nine papers supported the neuroprotective effect (6 human research, 58 animal/in vitro, 0 case reports, 25 review/opinion articles). A total of 116 papers supported the neurotoxic effect (17 human research, 23 animal/in vitro, 60 case reports, 16 review/opinion articles). Nine papers supported no hypothesis (5 human research, 3 animal/in vitro, 0 case reports, 1 review/opinion articles). Overall, the grading suggests that the data concerning the effect of lithium therapy is that of level C, that is 'unclear or conflicting scientific evidence' since there is conflicting evidence from uncontrolled non-randomized studies accompanied by conflicting evidence from animal and basic science studies. Although more papers are in favour of the toxic effect, the great difference in the type of papers that support either hypothesis, along with publication bias and methodological issues make conclusions difficult. Lithium remains the 'gold standard' for the prophylaxis of bipolar illness, however, our review suggests that there is a rare possibility of a neurotoxic effect in real-life clinical practice even in closely monitored patients with 'therapeutic' lithium plasma levels. It is desirable to keep lithium blood levels as low as feasible with prophylaxis.

Concurrent or Sequential Adjuvant Letrozole and Radiotherapy after Conservative Surgery for Early-stage Breast Cancer: Long-term Results of the Cohort Phase 2 Randomized Trial

Purpose/Objective(s): Letrozole radiosensitizes breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting.Materials/Methods: The present study is registered with ClinicalTrials.gov, number NCT00208273. This Phase 2 randomized trial was undertaken in two centers in France and one in Switzerland between January 12, 2005, and February 21, 2007. One hundred fifty postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n = 75) or sequential radiotherapy and letrozole (n = 75). Randomization was open label with a minimization technique, stratified by investigational centers, chemotherapy (yes vs. no), radiation boost (yes vs. no), and value of radiation-induced lymphocyte apoptosis (#16% vs. .16%). The whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal mammary node irradiation, the dose was 44 - 50 Gy. Letrozole was administered orally once daily at a dose of 2 - 5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks postradiotherapy in the sequential group). The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced Grade 2 or worse toxic effects of the skin and lung (functional pulmonary test and lung CT-scan). Analyses were by intention-to-treat. The long-term follow-up after 2 years was only performed in Montpellier (n = 121) and evaluated skin toxicity (clinical examination every 6 months), lung fibrosis (one CT-scan yearly), cosmetic outcome.Results: All patients were analyzed apart from 1 in the concurrent group who withdrew consent before any treatment.Within the first 2 years (n = 149), no lung toxicity was identified by CT scan and no modification from baseline was noted by the lung diffusion capacity test. Two patients in each group had Grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis [RISF]). After 2 years (n = 121), and with a median follow-up of 50 months (38-62), 2 patients (1 in each arm) presented a Grade 3 RISF. No lung toxicity was identified by CT scan. Cosmetic results (photographies) and quality of life was good to excellent. All patients who had Grade 3 subcutaneous fibrosis had an RILA value of 16% or less, irrespective of the sequence with letrozole.Conclusions:With long-term follow-up, letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy.

Local adaptation and life history traits evolution in heterogeneous environment : an empirical example in the freshwater snail, Galba truncatula

Abstract: To understand the processes of evolution, biologists are interested in the ability of a population to respond to natural or artificial selection. The amount of genetic variation is often viewed as the main factor allowing a species to answer to selection. Many theories have thus focused on the maintenance of genetic variability. Ecologists and population geneticists have long-suspected that the structure of the environment is connected to the maintenance of diversity. Theorists have shown that diversity can be permanently and stably maintained in temporal and spatial varying environment in certain conditions. Moreover, varying environments have been also theoretically demonstrated to cause the evolution of divergent life history strategies in the different niches constituting the environment. Although there is a huge number of theoretical studies selection and on life history evolution in heterogeneous environments, there is a clear lack of empirical studies. The purpose of this thesis was to. empirically study the evolutionary consequences of a heterogeneous environment in a freshwater snail Galba truncatula. Indeed, G. truncatula lives in two habitat types according the water availability. First, it can be found in streams or ponds which never completely dry out: a permanent habitat. Second, G. truncatula can be found in pools that freeze during winter and dry during summer: a temporary habitat. Using a common garden approach, we empirically demonstrated local adaptation of G. truncatula to temporary and permanent habitats. We used at first a comparison of molecular (FST) vs. quantitative (QST) genetic differentiation between temporary and permanent habitats. To confirm the pattern QST> FST between habitats suggesting local adaptation, we then tested the desiccation resistance of individuals from temporary and permanent habitats. This study confirmed that drought resistance seemed to be the main factor selected between habitats, and life history traits linked to the desiccation resistance were thus found divergent between habitats. However, despite this evidence of selection acting on mean values of traits between habitats, drift was suggested to be the main factor responsible of variation in variances-covariances between populations. At last, we found life history traits variation of individuals in a heterogeneous environment varying in parasite prevalence. This thesis empirically demonstrated the importance of heterogeneous environments in local adaptation and life history evolution and suggested that more experimental studies are needed to investigate this topic. Résumé: Les biologistes se sont depuis toujours intéressés en l'aptitude d'une population à répondre à la sélection naturelle. Cette réponse dépend de la quantité de variabilité génétique présente dans cette population. Plus particulièrement, les théoriciens se sont penchés sur la question du maintient de la variabilité génétique au sein d'environnements hétérogènes. Ils ont alors démontré que, sous certaines conditions, la diversité génétique peut se maintenir de manière stable et permanente dans des environnements variant au niveau spatial et temporel. De plus, ces environments variables ont été démontrés comme responsable de divergence de traits d'histoire de vie au sein des différentes niches constituant l'environnement. Cependant, malgré ce nombre important d'études théoriques portant sur la sélection et l'évolution des traits d'histoire de vie en environnement hétérogène, les études empiriques sont plus rares. Le but de cette thèse était donc d'étudier les conséquences évolutives d'un environnement hétérogène chez un esgarcot d'eau douce Galba truncatula. En effet, G. truncatula est trouvé dans deux types d'habitats qui diffèrent par leur niveau d'eau. Le premier, l'habitat temporaire, est constitué de flaques d'eau qui peuvent s'assécher pendant l'été et geler pendant l'hiver. Le second, l'habitat permanent, correspond à des marres ou à des ruisseaux qui ont un niveau d'eau constant durant toute l'année. Utilisant une approche expérimentale de type "jardin commun", nous avons démontré l'adaptation locale des individus à leur type d'habitat, permanent ou temporaire. Nous avons utilisé l'approche Fsr/QsT qui compare la différentiation génétique moléculaire avec la différentiation génétique quantitative entre les 2 habitats. Le phénomène d'adapation locale démontré par QsT > FsT, a été testé experimentalement en mesurant la résistance à la dessiccation d'individus d'habitat temporaire et permanent. Cette étude confirma que la résistance à la sécheresse a été sélectionné entre habitats et que les traits responsables de cette resistance sont différents entre habitats. Cependant si la sélection agit sur la valeur moyenne des traits entre habitats, la dérive génétique semble être le responsable majeur de la différence de variances-covariances entre populations. Pour finir, une variation de traits d'histoire de vie a été trouvée au sein d'un environnement hétérogène constitué de populations variants au niveau de leur taux de parasitisme. Pour conclure, cette thèse a donc démontré l'importance d'un environnement hétérogène sur l'adaptation locale et l'évolution des traits d'histoire de vie et suggère que plus d'études empiriques sur le sujet sont nécessaires.

Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span.

Children conceived by assisted reproductive technologies (ART) display a level of vascular dysfunction similar to that seen in children of mothers with preeclamspia. The long-term consequences of ART-associated vascular disorders are unknown and difficult to investigate in healthy children. Here, we found that vasculature from mice generated by ART display endothelial dysfunction and increased stiffness, which translated into arterial hypertension in vivo. Progeny of male ART mice also exhibited vascular dysfunction, suggesting underlying epigenetic modifications. ART mice had altered methylation at the promoter of the gene encoding eNOS in the aorta, which correlated with decreased vascular eNOS expression and NO synthesis. Administration of a deacetylase inhibitor to ART mice normalized vascular gene methylation and function and resulted in progeny without vascular dysfunction. The induction of ART-associated vascular and epigenetic alterations appeared to be related to the embryo environment; these alterations were possibly facilitated by the hormonally stimulated ovulation accompanying ART. Finally, ART mice challenged with a high-fat diet had roughly a 25% shorter life span compared with control animals. This study highlights the potential of ART to induce vascular dysfunction and shorten life span and suggests that epigenetic alterations contribute to these problems.