Publications by authors named "Javier Nieto"

228 Publications

Dimethylzinc-mediated enantioselective addition of terminal alkynes to 1,2-diketones using perhydro-1,3-benzoxazines as ligands.

Org Biomol Chem 2021 May;19(17):3859-3867

Instituto CINQUIMA and Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Valladolid, Paseo de Belén, 7, 47011 Valladolid, Spain.

A conformationally restricted perhydro-1,3-benzoxazine derived from (-)-8-aminomenthol behaves as a good chiral ligand in the dimethylzinc-mediated enantioselective monoaddition of aromatic and aliphatic terminal alkynes to 1,2-diketones. The corresponding α-hydroxyketones were obtained in good yields with high enantioselectivities starting from both aromatic and aliphatic 1,2-diketones. The alkynylation of unsymmetrical 1,2-diketones with electronically different substituents also proceeds with high regio- and enantioselectivity. This reaction provides a practical method to synthesize ketones bearing a chiral tertiary propargylic alcohol.
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http://dx.doi.org/10.1039/d1ob00249jDOI Listing
May 2021

The Survey of the Health of Wisconsin (SHOW) Program: An infrastructure for Advancing Population Health Sciences.

medRxiv 2021 Apr 7. Epub 2021 Apr 7.

Purpose: The Survey of the Health of Wisconsin (SHOW) was established in 2008 by the University of Wisconsin (UW) School of Medicine and Public Health (SMPH) with the goals of 1) providing a timely and accurate picture of the health of the state residents; and 2) serving as an agile resource infrastructure for ancillary studies. Today SHOW continues to serve as a vital population health research infrastructure.

Participants: SHOW currently includes 5,846 adult and 980 minor participants recruited between 2008-2019 in four primary waves. WAVE I (2008-2013) includes annual statewide representative samples of 3,380 adults ages 21 to 74 years. WAVE II (2014-2016) is a triannual statewide sample of 1957 adults (age ≥18 years) and 645 children. WAVE III (2017) consists of follow-up of 725 adults from the WAVE I and baseline surveys of 222 children in selected households. WAVEs II and III include stool samples collected as part of an ancillary study in a subset of 784 individuals. WAVE IV consist of 517 adults and 113 children recruited from traditionally under-represented populations in biomedical research including African Americans and Hispanics in Milwaukee county, WI.

Findings To Date: The SHOW provides extensive data to examine the intersectionality of multiple social determinants and population health. SHOW includes a large biorepository and extensive health data collected in a geographically diverse urban and rural population. Over 60 studies have been published covering a broad range of topics including, urban and rural disparities in cardio-metabolic disease and cancer, objective physical activity, sleep, green-space and mental health, transcriptomics, the gut microbiome, antibiotic resistance, air pollution, concentrated animal feeding operations and heavy metal exposures.

Future Plans: The SHOW cohort is available for continued longitudinal follow-up and ancillary studies including genetic, multi-omic and translational environmental health, aging, microbiome and COVID-19 research.

Article Summary: The Survey of the Health of Wisconsin (SHOW) is an infrastructure to advance population health sciences including biological sample collection and broader data on individual and neighborhood social and environmental determinants of health.The extensive data from diverse urban and rural populations offers a unique study sample to compare how socio-economic gradients shape health outcomes in different contexts.The objective health data supports novel interdisciplinary research initiatives and is especially suited for research in causes and consequences of environmental exposures (physical, chemical, social) across the life course on cardiometabolic health, immunity, and aging related conditions.The extensive biorepository supports novel omics research into common biological mechanisms underlying numerous complex chronic conditions including inflammation, oxidative stress, metabolomics, and epigenetic modulation.Ancillary studies, such as the Wisconsin Microbiome Study, have expanded the utility of the study to examine human susceptibility to environmental exposures and opportunities for investigations of the role of microbiome in health and disease.Long-standing partnerships and recent participation among traditionally under-represented populations in biomedical research offer numerous opportunities to support community-driven health equity work.No biological samples were collected among children.The statewide sampling frame may limit generalizability to other regions in the United States.
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http://dx.doi.org/10.1101/2021.03.15.21253478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043470PMC
April 2021

Positive affective states can play the role of context to renew extinguished instrumental behavior in rats.

Behav Processes 2021 Jun 23;187:104376. Epub 2021 Mar 23.

Philipps-Universität Marburg, Germany. Electronic address:

In one experiment with rats, we examined whether positive affective states can serve as contexts in a between-subjects ABA renewal design using appetitive instrumental conditioning. Two groups of rats received training to press a lever for food where each acquisition session was preceded by administration of a tickling procedure (Context A) known to induce positive affective states. Then, lever pressing underwent extinction where rats received a pure handling treatment (Context B) before each session. During a final test session, we found stronger responding when the session was preceded by tickling (Group ABA) compared to handling (Group ABB), indicating an ABA renewal effect. Furthermore, test performance in Group ABB was not different from that in a third group where handling preceded acquisition sessions, and tickling extinction and test sessions (Group BAA), showing that tickling did not elevate instrumental responding during the test if it had been unrelated to initial acquisition. We discuss implications of our results for understanding the role of positive affective states in relapse of problem behavior.
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http://dx.doi.org/10.1016/j.beproc.2021.104376DOI Listing
June 2021

A Novel Sampling Model to Study the Epidemiology of Canine Leishmaniasis in an Urban Environment.

Front Vet Sci 2021 8;8:642287. Epub 2021 Mar 8.

Área de Parasitología, Departamento de Agroquímica y Medio Ambiente, Universidad Miguel Hernández de Elche, Alicante, Spain.

Visceral leishmaniasis (VL) is one of the most important parasitic diseases in the world. The domestic dog is the main reservoir of zoonotic VL and a high prevalence of canine leishmaniasis (CanL) is associated with transmission of infection to humans. Here we describe the methodology used to obtain a rapid and representative sample of domestic dogs in the city of Posadas, Misiones, and compare the prevalence of infection with a sample of shelter dogs. We used the city land registry to make a random selection of homes and systematically recruited 349 domestic dogs from the selected properties. We also included all dogs from the main canine shelter within the city. Dogs were examined by two experienced veterinarians who recorded the presence of clinical signs common in CanL using a standardized protocol. We extracted a blood sample from each dog and performed four different serological tests to reveal the presence of anti- antibodies. After clinical examination, 145 domestic dogs (41.5%) and 63 (90%) shelter dogs had clinical signs compatible with CanL ( < 0.001). The seroprevalence among domestic dogs was 20.1% (95% CI 16.1-24.6) which was significantly lower than among the abandoned dogs (38.6%, 95% CI 27.7-50.6, < 0.001). The spatial distribution of infected dogs was fairly homogenous throughout the city. Among domestic dogs, we observed a positive association between where the dog slept and presence of anti- antibodies ( = 0.034). Of the seropositive domestic dogs 38 (54.4%) were asymptomatic. Our findings demonstrate how seroprevalence results can be highly influenced by sampling methodology. We demonstrate how the land registry can be used to estimate the prevalence of CanL in representative sample of domestic dogs in an urban setting, allowing decision makers to deepen their understanding the epidemiology of CanL in a timely and efficient manner for the development of plans to address both human and canine disease.
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http://dx.doi.org/10.3389/fvets.2021.642287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982517PMC
March 2021

Evaluation of the Performance of the Loopamp Trypanosoma cruzi Detection Kit for the Diagnosis of Chagas Disease in an Area Where It Is Not Endemic, Spain.

J Clin Microbiol 2021 04 20;59(5). Epub 2021 Apr 20.

Foundation for Innovative New Diagnostics FIND, Geneva, Switzerland.

In Spain, PCR is the tool of choice for the diagnosis of congenital Chagas disease (CD) and serology for diagnosing chronic CD. A loop-mediated isothermal amplification test for DNA detection showed good analytical performance and ease of use. We aimed to evaluate the performance of the Loopamp detection kit (Eiken Chemical Co. Ltd., Japan) (-LAMP) for congenital and chronic CD diagnosis using well-characterized samples. We included samples from 39 congenital and 174 chronic CD cases and from 48 uninfected children born to infected mothers and 34 nonchagasic individuals. The sensitivity, specificity, and accuracy of -LAMP were estimated using standard case definitions for congenital CD (positive result by parasitological or PCR tests or serology after 9 months of age) and chronic CD (positive serology by at least two tests). The -LAMP results were read by visual examination and a real-time fluorimeter. For congenital CD, -LAMP sensitivity was 97% for both types of reading; specificity was 92% by visual examination and 94% by fluorimeter. For chronic CD, sensitivity was 47% and specificity 100%. The accuracy in congenital CD was >94% versus 56% in chronic CD. The agreement of -LAMP with PCR tests was better in congenital CD (kappa, 0.86 to 0.91) than in chronic CD (kappa, 0.67 to 0.83). The Loopamp detection kit showed good performance for the diagnosis of congenital CD. -LAMP, like PCR, can be useful for the screening and early diagnosis of congenital infection.
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http://dx.doi.org/10.1128/JCM.01860-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091841PMC
April 2021

Oral decontamination with colistin plus neomycin in solid organ transplant recipients colonized by multidrug-resistant Enterobacterales: a multicentre, randomized, controlled, open-label, parallel-group clinical trial.

Clin Microbiol Infect 2021 Jun 24;27(6):856-863. Epub 2020 Dec 24.

Quality Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.

Objectives: To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients.

Methods: Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed.

Results: MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24-2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea.

Conclusions: DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.
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http://dx.doi.org/10.1016/j.cmi.2020.12.016DOI Listing
June 2021

Antileishmanial efficacy and tolerability of combined treatment with non-ionic surfactant vesicle formulations of sodium stibogluconate and paromomycin in dogs.

Exp Parasitol 2021 Jan 7;220:108033. Epub 2020 Nov 7.

Cátedra de Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, Avenida Puerta del Hierro s/n, Ciudad Universitaria, 28040, Madrid, Spain.

Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine leishmaniasis (CanL) do not cause complete parasite clearance; they can be toxic, and emerging drug resistance in parasite populations limits their clinical utility. Therefore, in this study we have evaluated the toxicity and efficacy of joint treatment with a 1:1 mixture of sodium stibogluconate-NIV (SSG-NIV, 10 mg Sb/day) and paromomycin-NIV (PMM-NIV, 10 mg PMM/kg/day), given intravenously daily for seven days from day 270 post-infection, to nine-month-old female beagle dogs (n = 6) experimentally infected with Leishmania infantum. Treatment significantly improved the clinical symptoms of VL infection in all the treated dogs, reduced parasite burdens in lymph nodes and bone marrow, and all symptomatic treated dogs, were asymptomatic at 90 days post-treatment. Treatment was associated with a progressive and significant decrease in specific IgG anti-Leishmania antibodies using parasite soluble antigen (p < 0.01) or rK39 (p < 0.01) as the target antigen. In addition, all dogs were classified as parasite negative based on Leishmania nested PCR and quantitative real time PCR tests and as well as an inability to culture of promastigote parasites from lymph nodes and bone marrow tissue samples taken at day 90 post-treatment. However, treatment did not cure the dogs as parasites were detected at 10 months post-treatment, indicating that a different dosing regimen is required to cause long term cure or prevent relapse.
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http://dx.doi.org/10.1016/j.exppara.2020.108033DOI Listing
January 2021

Gut Microbiome in Children from Indigenous and Urban Communities in México: Different Subsistence Models, Different Microbiomes.

Microorganisms 2020 Oct 16;8(10). Epub 2020 Oct 16.

Neuroecology Lab, Facultad de Psicología, UNAM, Mexico City 04510, Mexico.

The human gut microbiome is an important component that defines host health. Childhood is a particularly important period for the establishment and development of gut microbiota (GM). We sequenced the 16S rRNA gene from fecal samples of children between 5 and 10 years old, in two Mexican communities with contrasting lifestyles, i.e., "Westernized" (México City, = 13) and "non-Westernized" (Me'phaa indigenous group, = 29), in order to characterize and compare their GM. The main differences between these two communities were in bacteria associated with different types of diets (high animal protein and refined sugars vs. high fiber food, respectively). In addition, the GM of Me'phaa children showed higher total diversity and the presence of exclusive phyla, such as Deinococcus-Thermus, Chloroflexi, Elusimicrobia, Acidobacteria, and Fibrobacteres. In contrast, the children from México City showed less diversity and the presence of Saccharibacteria phylum, which was associated with the degradation of sugar compounds and was not present in the samples from Me'phaa children. This comparison provided further knowledge of the selective pressures affecting microbial ecosystemic composition over the course of human evolution and the potential consequences of pathophysiological states correlated with Westernization lifestyles.
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http://dx.doi.org/10.3390/microorganisms8101592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602701PMC
October 2020

Adherence to Human Colon Cells by Multidrug Resistant Strains Isolated From Solid Organ Transplant Recipients With a Focus on .

Front Cell Infect Microbiol 2020 16;10:447. Epub 2020 Sep 16.

Instituto de Investigación Valdecilla-IDIVAL, Santander, Spain.

Enterobacteria species are common causes of hospital-acquired infections, which are associated with high morbidity and mortality rates. Immunocompromised patients such as solid organ transplant (SOT) recipients are especially at risk because they are frequently exposed to antibiotics in the course of their treatments. In this work, we used a collection of 106 , 78 , 25 spp., and 24 spp. multidrug resistant strains isolated from transplant patients (hepatic, renal or renal/pancreatic) in order to examine their ability to adhere to HT-29 human colon cells, and to determine if some adhesive characteristics are associated with prevalence and persistence of these strains. A total of 33 (31%), 21 (27%), 7 spp. (28%), and 5 spp. (21%), adhered to the colon epithelial cells. Two main adherence patterns were observed in the four species analyzed, diffuse adherence, and aggregative adherence. Under transmission electronic microscopy (TEM), most bacteria lacked visible fimbria on their surface, despite their strong adherence to epithelial cells. None of the strains studied was able to induce any cytotoxic effect on HT-29 cells although some of them strongly colonizing both cells and glass coverslips at high density. Some of the strains failed to adhere to the epithelial cells but adhered strongly to the cover-slide, which shows that microscopy studies are mandatory to elucidate the adherence of bacteria to epithelial cells , and that quantitative assays using colony forming unit (CFUs) counting need to be supplemented with pictures to determine definitively if a bacterial strain adheres or not to animal cells . We report here, for the first time, the aggregative adherence pattern of two multidrug resistant (MDR) strains isolated from human patients; importantly, biofilm formation in is totally dependent on the temperature; strong biofilms were formed at room temperature (RT) but not at 37°C, which can play an important role in the colonization of hospital surfaces. In conclusion, our results show that there is a great variety of adhesion phenotypes in multidrug-resistant strains that colonize transplanted patients.
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http://dx.doi.org/10.3389/fcimb.2020.00447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525035PMC
June 2021

Conducting extinction in multiple contexts attenuates relapse of operant behavior in humans.

Behav Processes 2020 Dec 3;181:104261. Epub 2020 Oct 3.

Universidad de Córdoba, Spain.

In one experiment with human participants, we investigated the effects of using multiple contexts during extinction on the renewal of operant responses. Undergraduate students played a videogame in which they learned to shoot at enemies in Context A. Then, all participants experienced an extinction training. For half of the participants, extinction trials were conducted in a single context, whereas the other half received extinction in three different contexts. Finally, all participants were tested in Context A. We observed that conducting extinction in multiple contexts attenuated ABA renewal. The present results suggest that conducting extinction in multiple contexts can be used as a behavioral technique to reduce operant renewal.
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http://dx.doi.org/10.1016/j.beproc.2020.104261DOI Listing
December 2020

Reasons Behind Preferences for Community-Based Continence Promotion.

Female Pelvic Med Reconstr Surg 2020 07;26(7):425-430

Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Objectives: This study aimed to understand the potential reach of continence promotion intervention formats among incontinent women.

Methods: The Survey of the Health of Wisconsin conducts household interviews on a population-based sample. In 2016, 399 adult women were asked about incontinence and likelihood of participation in continence promotion via 3 formats: single lecture, interactive 3-session workshop, or online. Descriptive analyses compared women likely versus unlikely to participate in continence promotion. To understand format preferences, modified grounded theory was used to conduct and analyze telephone interviews.

Results: One hundred eighty-seven (76%) of 246 incontinent women reported being likely to attend continence promotion: 111 (45%) for a single lecture, 43 (17%) for an interactive 3-session workshop, and 156 (64%) for an online program. Obesity, older age, nonwhite race, prior health program participation, and Internet use for health information were associated with reported continence promotion participation. Cited advantages of a single lecture included convenience and ability to ask questions. A workshop offered accountability, hands-on learning, and opportunity to learn from others; online format offered privacy, convenience, and self-directed learning.

Conclusions: Most incontinent women are willing to participate in continence promotion, especially online.
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http://dx.doi.org/10.1097/SPV.0000000000000806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329600PMC
July 2020

Self-reported Health is Related to Body Height and Waist Circumference in Rural Indigenous and Urbanised Latin-American Populations.

Sci Rep 2020 03 9;10(1):4391. Epub 2020 Mar 9.

Neuroecology Lab, Faculty of Psychology, National Autonomous University of Mexico, Mexico City, Mexico.

Body height is a life-history component. It involves important costs for its expression and maintenance, which may originate trade-offs on other costly components such as reproduction or immunity. Although previous evidence has supported the idea that human height could be a sexually selected trait, the explanatory mechanisms that underlie this selection are poorly understood. Despite extensive studies on the association between height and attractiveness, the role of immunity in linking this relation is scarcely studied, particularly in non-Western populations. Here, we tested whether human height is related to health measured by self-perception, and relevant nutritional and health anthropometric indicators in three Latin-American populations that widely differ in socioeconomic and ecological conditions: two urbanised populations from Bogota (Colombia) and Mexico City (Mexico), and one isolated indigenous population (Me'Phaa, Mexico). Results showed that self-reported health is best predicted by an interaction between height and waist circumference: the presumed benefits of being taller are waist-dependent, and affect taller people more than shorter individuals. If health and genetic quality cues play an important role in human mate-choice, and height and waist interact to signal health, its evolutionary consequences, including cognitive and behavioural effects, should be addressed in future research.
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http://dx.doi.org/10.1038/s41598-020-61289-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062753PMC
March 2020

Disturbance in human gut microbiota networks by parasites and its implications in the incidence of depression.

Sci Rep 2020 02 28;10(1):3680. Epub 2020 Feb 28.

NeuroEcology Lab, Faculty of Psychology, National Autonomous University of Mexico (UNAM), Mexico City, México.

If you think you are in control of your behavior, think again. Evidence suggests that behavioral modifications, as development and persistence of depression, maybe the consequence of a complex network of communication between macro and micro-organisms capable of modifying the physiological axis of the host. Some parasites cause significant nutritional deficiencies for the host and impair the effectiveness of cognitive processes such as memory, teaching or non-verbal intelligence. Bacterial communities mediate the establishment of parasites and vice versa but this complexity approach remains little explored. We study the gut microbiota-parasite interactions using novel techniques of network analysis using data of individuals from two indigenous communities in Guerrero, Mexico. Our results suggest that Ascaris lumbricoides induce a gut microbiota perturbation affecting its network properties and also subnetworks of key species related to depression, translating in a loss of emergence. Studying these network properties changes is particularly important because recent research has shown that human health is characterized by a dynamic trade-off between emergence and self-organization, called criticality. Emergence allows the systems to generate novel information meanwhile self-organization is related to the system's order and structure. In this way, the loss of emergence means a depart from criticality and ultimately loss of health.
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http://dx.doi.org/10.1038/s41598-020-60562-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048763PMC
February 2020

Ankle-brachial index and arterial vascular events in systemic lupus erythematosus patients: a 5-year prospective cohort.

Clin Exp Rheumatol 2020 Sep-Oct;38(5):978-984. Epub 2020 Feb 4.

Department of Internal Medicine, Hospital Universitario Cruces, University of The Basque Country, Bizkaia, Spain.

Objectives: To determine the potential predictive value in patients with systemic lupus erythematous of the ankle-brachial index (ABI) for the occurrence of arterial vascular events.

Methods: 216 lupus patients from a prospective clinical cohort were evaluated using the ABI at the start of the study and then followed up for 5 years. Abnormal ABI was defined as an index ≤0.9 or >1.4. Several potential vascular risk factors were also evaluated. Arterial vascular events (AVE): coronary events, cerebrovascular events, peripheral arterial disease and death related to vascular disease. Survival analysis was performed using a competitive risk regression approach, considering non-vascular death as a competitive event.

Results: 18 arterial events and 14 deaths were identified. In the competitive risk regression analysis, independent predictors of higher risk were identified: family history of early AVE [subdistribution hazard ratio (SHR) 5.44, 95% confidence interval (CI) 1.69-17.50, p=0.004)], cumulative prednisone (grams) (SHR 1.01, 95% CI 1.01-1.03, p=0.007) and a personal history of arterial thrombosis (SHR 5.44, 95% CI 1.45-14.59, p=0.004). Female gender was a protective factor (SHR 0.22, 95% CI 0.07-0.77, p=0.017). A statistical trend was detected with abnormal ABI (SHR 2.65, 95% CI 0.86-8.14, p=0.089).

Conclusions: Male gender, exposure to high cumulative doses of prednisone, family history of early arterial vascular disease and occurrence of previous arterial thrombosis are independent risk predictors of arterial vascular events in patients with systemic lupus erythematosus. Abnormal ABI may be related to high risk for arterial vascular events.
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October 2020

The impacts of acquisition and extinction cues on ABC renewal of voluntary behaviors.

Learn Mem 2020 03 18;27(3):114-118. Epub 2020 Feb 18.

Department of Psychology, Philipps-Universität Marburg, Marburg 35032, Germany.

In two instrumental conditioning experiments with rats, we examined the impacts of acquisition and extinction cues on ABC renewal of instrumental behavior. Animals were reinforced with food for lever pressing in one context, followed by extinction of the response in a second one. Presentations of a brief tone accompanied extinction in Experiment 1 (extinction cue), and acquisition in Experiment 2 (acquisition cue). A final test in a third context revealed that instrumental responding was decreased in the presence of the extinction cue, whereas it was increased in the presence of the acquisition cue. We discuss theoretical and clinical implications of our results.
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http://dx.doi.org/10.1101/lm.050831.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029720PMC
March 2020

Perspectives on the Future of Epidemiology: A Framework for Training.

Am J Epidemiol 2020 07;189(7):634-639

Over the past century, the field of epidemiology has evolved and adapted to changing public health needs. Challenges include newly emerging public health concerns across broad and diverse content areas, new methods, and vast data sources. We recognize the need to engage and educate the next generation of epidemiologists and prepare them to tackle these issues of the 21st century. In this commentary, we suggest a skeleton framework upon which departments of epidemiology should build their curriculum. We propose domains that include applied epidemiology, biological and social determinants of health, communication, creativity and ability to collaborate and lead, statistical methods, and study design. We believe all students should gain skills across these domains to tackle the challenges posed to us. The aim is to train smart thinkers, not technicians, to embrace challenges and move the expanding field of epidemiology forward.
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http://dx.doi.org/10.1093/aje/kwaa013DOI Listing
July 2020

Individuals' perceptions of social support from family and friends are associated with lower risk of sleep complaints and short sleep duration.

Sleep Health 2020 02 16;6(1):110-116. Epub 2019 Nov 16.

Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. Electronic address:

Objective: To examine whether individuals' perceptions of social support (SS) from partners, other family members, and friends are associated with risk of sleep complaints and short sleep duration.

Methods: A cross-sectional and prospective study with 1,688 community dwelling adults from the Retirement and Sleep Trajectories study. Four annual, self-administered questionnaires were mailed to participants in the year 2010-2014. Self-reports of individuals' perceptions of SS were obtained at the baseline survey. Sleep quality and duration were self-reported on each of the four surveys over the follow-up. Associations were examined with mixed-effect models, controlling for confounders.

Results: In fully adjusted analyses, compared with those reporting low SS from their partner, the risk of reporting more than 1 sleep symptom was significantly lower among those with intermediate (relative risk, RR = 0.68; 95% confidence interval, CI = 0.53-0.87) and high SS (RR = 0.61; 95% CI=0.48-0.77). Similarly, relative to those with low SS, those reporting high SS from family (RR = 0.74; 95% CI = 0.57-0.94) and friends (RR = 0.73; 95% CI = 0.58-0.92) had lower risk of having more than 1 sleep symptom. Compared with those with low, intermediate (RR = 0.70; 95% CI = 0.52-0.96), and high SS (RR = 0.63; 95% CI = 0.48-0.84) from partners, intermediate (RR = 0.76; 95% CI = 0.59-0.97) and high SS (RR = 0.69; 95% CI = 0.51-0.92) from family and high SS (RR = 0.74; 95% CI = 0.56-0.99) from friends were associated with lower risk of short sleep (≤6 h).

Conclusion: The perception of higher SS from relatives and friends is independently associated with lower risk of poor sleep quality and short sleep duration. Future research and intervention studies should test whether strengthening social relationships can positively effect sleep health.
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http://dx.doi.org/10.1016/j.sleh.2019.08.013DOI Listing
February 2020

One-year changes in self-reported napping behaviors across the retirement transition.

Sleep Health 2019 12 11;5(6):639-646. Epub 2019 Nov 11.

Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI. Electronic address:

Objective: To estimate associations of retirement with self-reported frequency and duration of naps.

Design: Prospective cohort study.

Setting: Population-based.

Participants: 1359 current and former Wisconsin state employees, aged 54-69.

Measurements: Four annual surveys mailed between 2010 and 2014 elicited employment status and nap characteristics. Changes in employment status and nap characteristics were identified from survey pairs measured 1 year apart (up to 3 survey pairs per subject). General linear mixed models with repeated measures were used to estimate changes in minutes napped per week (MNPW), weekly nap frequency, and individual nap duration as predicted by retirement transitions vs stable employment status. All models were adjusted for demographic characteristics, self-rated health, medical diagnoses, sleep problems, circadian preference, and change in nocturnal sleep duration.

Results: There were 3101 survey pairs in the analytic sample. Full retirement (transition from working ≥35 h/wk to not working for pay) over a 1-year period predicted a statistically significantly larger mean change in MNPW than stable employment status: mean (95% confidence interval) = +48 (+16, +80) MNPW. Associations between staged retirement transitions (from full-time to part-time work, or from part-time work to full retirement) and 1-year changes in MNPW were not statistically significant. The MNPW changes associated with full retirement were attributable to nap frequency increase of +0.4 (+0.1, +0.8) d/wk; nap duration did not change significantly.

Conclusions: Compared with stable employment status, full retirement is associated with an average 1-year increase of +48 MNPW. This change is attributable to a frequency gain of 0.4 d/wk napped. Changes in nap duration were negligible.
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http://dx.doi.org/10.1016/j.sleh.2019.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962139PMC
December 2019

The Use of Specific Serological Biomarkers to Detect CaniLeish Vaccination in Dogs.

Front Vet Sci 2019 24;6:373. Epub 2019 Oct 24.

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

Canine leishmaniosis (CanL) prevention in the Mediterranean basin is considered essential to stop human zoonotic visceral leishmaniasis. In this context, vaccination of dogs is expected to have a significant impact in disease control. CaniLeish® (Virbac Animal Health) is one of a few CanL vaccines that are at this moment licensed in Europe. This vaccine contains purified excreted-secreted proteins of having several antigens/immunogens with potential to influence serological response. Therefore, it is important to know if CaniLeish vaccination increased the diagnostic challenges associated with conventional serology, limiting the value of some antigens. To address this 20 dogs from a cohort of 35 healthy dogs that were vaccinated, maintained indoor for 1 month and then returned to their natural domiciles for 2 years. After this period, they were re-called to evaluate their clinical/parasitological condition and assess the evolution of seroreactivity against different antigens: soluble promastigote antigens (SPLA), recombinant protein cytosolic peroxiredoxin, recombinant protein K39 (rK39), recombinant protein K28 and recombinant kinesin degenerated derived repeat using ELISA. Two years after vaccination all vaccinated non-infected animals were seropositive for SPLA. For the other antigens the serological profile was indistinguishable from non-infected animals. Moreover, vaccinated animals presented a characteristic relative serological profile, with higher normalized serological response to SPLA than rK39. This fact enabled to distinguish with sensitivity 92.3% and specificity 95.4%, vaccinated non-infected dogs from infected and non-infected dogs. Ultimately, relative serological profile enabled the detection of healthy vaccinated animals enabling more accurate serological surveys.
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http://dx.doi.org/10.3389/fvets.2019.00373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821643PMC
October 2019

Actigraphic Sleep and Dietary Macronutrient Intake in Children Aged 6-9 Years Old: A Pilot Study.

Nutrients 2019 Oct 24;11(11). Epub 2019 Oct 24.

Unit of Preventive Medicine and Public Health, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine, University of Valencia, Avda. Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.

The objective of this study was to examine the relationship between different sleep parameters and energy and macronutrient intake in school-aged children. A total of 203 children 6 to 9 years of age participated in this cross-sectional study. Anthropometric measurements were taken first. Diet was assessed with 3-day food logs and sleep was measured with a questionnaire on sleep quality and a wrist actigraph worn for at least 7 days. A decrease of 165.45 kcal was observed per each additional hour of sleep during the week (β (95% CI) = -165.45 (-274.01, -56.88); = 0.003). This relationship was also observed for fat (β (95% CI) = -11.14 (-18.44, -3.84); = 0.003) and protein (β (95% CI) = -13.27 (-22.52, -4.02); = 0.005). An increase in weekend sleep efficiencies for those under the recommended threshold of 85% also had a similar association with energy (β (95% CI) = -847.43 (-1566.77, 128.09); = 0.021) and carbohydrate (β (95% CI) = -83.96 (-161.76, -6.15); = 0.035)) intake. An increase in habitual sleep variability was related with a slight increase in protein intake (β (95% CI) = 0.32 (0.031, 0.62); = 0.031). Children who slept less had a higher energy intake, especially from fat and protein and those who presented inefficient sleep had a higher carbohydrate intake. Strategies to enhance sleep quality and quantity combined with dietary recommendations could help to improve energy and macronutrient intake levels in children.
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http://dx.doi.org/10.3390/nu11112568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893783PMC
October 2019

Estimated Annual Health and Cost Impact of PHiD-CV Immunization Program in Brazil.

Pediatr Infect Dis J 2019 10;38(10):e260-e265

GSK Vaccines, Panamá City, Panamá.

Background: Streptococcus pneumoniae causes invasive pneumococcal disease (IPD), community-acquired pneumonia (CAP) and acute otitis media (AOM). Two higher-valent pneumococcal conjugate vaccines (PCV) are available, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and 13-valent PCV (PCV-13). This study estimated the economic and health impact of PHiD-CV vaccination on pneumococcal disease burden in children <5 years of age in Brazil.

Methods: The disease burden prior to the PHiD-CV vaccination program was estimated from literature and databases. The effect of PHiD-CV was estimated as a reduction of 70% for IPD, 26% for CAP and 40% for AOM, based on published studies. Residual IPD cases attributable to serotype 19A were estimated using surveillance data. PCV-13 effectiveness against 19A-IPD was set at 30%-70% higher than PHiD-CV. Vaccine prices were US$12.85/dose for PHiD-CV and US$14.50/dose for PCV-13.

Results: PHiD-CV vaccination reduced IPD by 6359, CAP by 315,016 and AOM by 669,943 cases, with estimated cost savings of >US$84 million annually and US$211-22,232 per case averted depending on the outcome. Switching from PHiD-CV to PCV-13 would avoid only a few additional IPD cases at additional costs exceeding US$18 million per year (US$125,192-386,230 per IPD case averted).

Conclusions: The PHiD-CV vaccination program in Brazil has resulted in important reductions of pneumococcal disease and substantial cost savings. Instead of switching PCVs, expanding vaccine coverage or investing in other health care interventions would be a more efficient use of resources to improve the health of the population in Brazil.
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http://dx.doi.org/10.1097/INF.0000000000002436DOI Listing
October 2019

Prevalence of asymptomatic infection and associated risk factors, after an outbreak in the south-western Madrid region, Spain, 2015.

Euro Surveill 2019 May;24(22)

WHO Collaborating Centre for Leishmaniasis, National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

BackgroundA large outbreak of leishmaniasis with 758 cutaneous and visceral leishmaniasis cases occurred in 2009 in Fuenlabrada, in the south-west of the Madrid region of Spain.AimWe aimed to determine the prevalence of asymptomatic infection after this outbreak, and its associated risk factors.MethodsA cross-sectional study of 804 healthy individuals living in Fuenlabrada who had no history of leishmaniasis, was conducted between January and July 2015. Asymptomatic infections were sought by either a combination of PCR, immunofluorescent antibody titre, and direct agglutination tests, or by whole blood stimulation assay (WBA) with interleukin-2 (IL-2) quantification.ResultsUsing the first approach, prevalence of asymptomatic individuals was 1.1% (9/804), while the second returned a value of 20.7% (143/804). Older age, being male, proximity to the park where the focus of infection was identified, and living in a detached house, were all strongly associated with the prevalence of asymptomatic infection.ConclusionsThe true number of infected individuals may be underestimated if only serological methods are used. The combination of WBA with IL-2 quantification may allow to better determine the prevalence of asymptomatic infection, which would be useful in establishing control measures and in quantifying their impact. In our study, the use of WBA with IL-2 quantification also helped establish the risk factors that influence exposure to and infection by .
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.22.1800379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549460PMC
May 2019

Role of age and comorbidities in mortality of patients with infective endocarditis.

Eur J Intern Med 2019 Jun 21;64:63-71. Epub 2019 Mar 21.

Hospital Universitario de Cruces, Bilbao, Spain.

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality.

Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk.

Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality.

Conclusion: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group.
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http://dx.doi.org/10.1016/j.ejim.2019.03.006DOI Listing
June 2019

Response to article by Matthew Wasserman et al. (2018): "Modeling the sustained use of the 13-valent pneumococcal conjugate vaccine compared to switching to the 10-valent vaccine in Mexico".

Hum Vaccin Immunother 2019 20;15(3):570-571. Epub 2018 Dec 20.

c Medical Affairs Department , GSK , Panama City , Panama.

In a recent article, Wasserman et al. estimated and forecasted the health and economic impact of switching from the 13-valent (PCV-13) to the 10-valent (PHiD-CV) pneumococcal conjugate vaccine in Mexico's national immunization program. In this response letter, we highlight various methodological inconsistencies and model input considerations that potentially bias the results and further recommendations made by the authors.
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http://dx.doi.org/10.1080/21645515.2018.1554974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988871PMC
October 2019

Cellular Markers of Active Disease and Cure in Different Forms of -Induced Disease.

Front Cell Infect Microbiol 2018 13;8:381. Epub 2018 Nov 13.

WHO Collaborating Centre for Leishmaniasis, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

Increased numbers of peripheral blood mononucleocytes (PBMC) and increased IFN-γ secretion following challenge of blood samples with soluble antigen (SLA), have been proposed as biomarkers of specific cell-mediated immunity, indicating that treatment of visceral leishmaniasis (VL) has been successful. However, infection may manifest as cutaneous leishmaniasis (CL), and less commonly as localized leishmanial lymphadenopathy (LLL) or mucosal leishmaniasis (ML). The present work examines the value of these biomarkers as indicators of cured leishmaniasis presenting in these different forms. Blood samples were collected before and after treatment from patients living in Fuenlabrada (Madrid, Spain), an endemic area recently the center of a leishmaniasis outbreak. All samples were subjected to -specific PCR, serological tests (IFAT and rK39-ICT), and the SLA-cell proliferation assay (SLA-CPA), recording PBMC proliferation and the associated changes in IFN-γ production. Differences in the results recorded for the active and cured conditions were only significant for VL. PCR returned positive results in 67% of patients with active VL and in 3% of those with cured leishmaniasis. Similarly, rK39-ICT returned a positive result in 77% of active VL samples . 52% in cured VL samples, and IFAT in 90% . 56%; in the SLA-CPA, PBMC proliferation was seen in 16% . 90%, and an associated increase in IFN-γ production of 14 and 84%, respectively. The present findings reinforce the idea that PBMC proliferation and increased IFN-γ production in SLA-stimulated PBMC provide biomarkers of clinical cure in VL. Other tests are urgently needed to distinguish between the cured and active forms of the other types of clinical leishmaniasis caused by .
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http://dx.doi.org/10.3389/fcimb.2018.00381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243388PMC
September 2019

Extinction makes acquisition context-specific in conditioned taste aversion regardless of the context where acquisition and testing take place.

J Exp Psychol Anim Learn Cogn 2018 Oct;44(4):385-395

Faculty of Psychology, Universidad Nacional Autonoma de Mexico.

Retrieval of a flavor-illness association has been found to show contextual dependence when the association is learned after a nontarget flavor-illness association has been extinguished in what has been named as the extinction makes acquisition context-specific (EMACS) effect. Four experiments were designed to further explore the EMACS effect in conditioned taste aversion. Experiments 1 and 2 replicated the EMACS effect using rats that did not experience extinction, and rats that underwent extinction of a different flavor as controls. Experiments 3 and 4 found that the experience of extinction with the nontarget Flavor X in a given context (A) led to context-specificity of performance to the target Flavor Y both, when Y was trained in a highly familiar context (B) and tested in the context where X had been trained (Context A, Experiment 3), and when the test was conducted in a less familiar context (C) where no cues or outcomes were presented before (Experiment 4). These results are consistent with the idea that the experience of extinction encourages organism's attention to the contexts, making retrieval of new learning context-specific. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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http://dx.doi.org/10.1037/xan0000183DOI Listing
October 2018

Indications and use of, and incidence of major bleeding with, antithrombotic agents in myelodysplastic syndrome.

Leuk Res 2018 10 31;73:24-28. Epub 2018 Aug 31.

Department of Hematology, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Spain.

Myelodysplastic syndrome (MDS) and antithrombotic medication both increase the risk of bleeding. We set out to analyze the prevalence of use, indications and bleeding risk of antithrombotic therapy in patients with MDS in a retrospective, single-center study including all patients with MDS with >20 × 10/L platelets. 193 patients (59% male, median age 75 years) were included; 122 did not receive antithrombotic treatment, 51 received antiplatelet agents and 20 received anticoagulants. The cumulative incidence of major bleeding was higher in both the antiplatelet group (11.8% at 4 years, 95% confidence interval [95%CI]: 4.7-22.3%) and the anticoagulation group (21.2% at 4 years, 95%CI 6-42.5%) than in the control group (2.8% at 4 years 95%CI: 0.7-7.3%). The prevalence of use of antithrombotic medication in this cohort of patients with MDS was high and bleeding risk was increased in these patients.
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http://dx.doi.org/10.1016/j.leukres.2018.08.017DOI Listing
October 2018

Venous thrombosis and relapses in patients with Behçet's disease. Descriptive analysis from Spanish network of Behçet's disease (REGEB cohort).

Clin Exp Rheumatol 2018 Nov-Dec;36(6 Suppl 115):40-44. Epub 2018 May 3.

Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain.

Objectives: To describe the characteristics of patients with Behçet's disease (BD) who presented with venous thrombosis. In addition, we identified the factors associated with this venous involvement and those related with recurrent venous thrombosis.

Methods: Up to January 2015, 544 BD patients from 20 Spanish hospitals had been included in the REGEB (REGistro de la Enfermedad de Behçet as Spanish nomenclature). We selected those patients who presented venous thrombosis. Descriptive analysis was performed and factors related with venous thrombosis were identified.

Results: Overall, 99 (18.2%) BD patients had vascular thrombosis, 91 (16.7%) of them (16.7%) involving venous vessels and 18 (19.7%) suffered from venous thrombotic relapse. Lower limbs were the most common location of deep venous thrombosis present in up to 60% of patients. In 12 (13.2%) patients, venous thrombosis affected two vascular territories simultaneously and in 6 (6.6%) the venous and arterial involvement coincided in time. Overall, at the diagnosis of venous thrombosis, 97.6% of patients presented concomitantly other clinical symptoms attributable to BD. In logistic regression multivariate analysis factors associated to venous thrombosis were male sex (Odds ratio [OR] 4.3, 95% confidence interval [CI] 2.5-7.7), erythema nodosum (OR 2.4, 95%CI 1.4-4.1), fever (OR 2.0, 95%CI 1.1-3.8), and central nervous system (CNS) involvement (OR 2.5, 95%CI 1.3-4.8). Considering relapses, CNS involvement was an independent risk factor according logistic regression. However, Cox multivariate analysis did not confirm this finding.

Conclusions: We identified factors related with venous involvement in patients included in the REGEB cohort.
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March 2019

Predictors of discordance in self-report versus device-measured physical activity measurement.

Ann Epidemiol 2018 07 30;28(7):427-431. Epub 2018 Mar 30.

Department of Kinesiology, University of Wisconsin-Madison, Madison. Electronic address:

Purpose: Accurate measurement of free-living physical activity is challenging in population-based research, whether using device-based or reported methods. Our purpose was to identify demographic predictors of discordance between physical activity assessment methods and to determine how these predictors modify the discordance between device-based and reported physical activity measurement methods.

Methods: Three hundred forty-seven adults from the Survey of the Health of Wisconsin wore the ActiGraph accelerometer for 7 days and completed the Global Physical Activity Questionnaire. Multivariate linear regression was conducted to assess predictors of discordance including gender, education, body mass index, marital status, and other individual level characteristics in physical activity reporting.

Results: Seventy-seven percent of men and 72% of women self-reported meeting the U.S. Centers for Disease Control and Prevention guidelines for aerobic activity but when measured by accelerometer, only 21% of men and 17% of women met guidelines. Demographic characteristics that predicted discordance between methods in multivariate regression included greater educational attainment (P < .001) and partnered status (P = .003).

Conclusions: These varying levels of discordance imply that comparisons of self-reported activity among groups defined by (or substantially varying by) educational attainment or marital status should be done with considerable caution as observed differences may be due, in part, to systematic, differential measurement biases among groups.
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http://dx.doi.org/10.1016/j.annepidem.2018.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500726PMC
July 2018
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