Últimos itens adicionados do Acervo: Harvard University

A Universidade de Harvard (em inglês: Harvard University) é uma universidade privada membro da Ivy League, localizada em Cambridge, Massachusetts, Estados Unidos, e cuja história, influência e riqueza tornam-a uma das mais prestigiadas universidades do mundo.

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Neural Activity During Social Signal Perception Correlates With Self-reported Empathy

Hooker, Christine; Verosky, Sara C.; Germine, Laura Thi; Knight, Robert T.; D'Esposito, Mark
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
EN_US
Empathy is an important component of human relationships, yet the neural mechanisms that facilitate empathy are unclear. The broad construct of empathy incorporates both cognitive and affective components. Cognitive empathy includes mentalizing skills such as perspective-taking. Affective empathy consists of the affect produced in response to someone else's emotional state, a process which is facilitated by simulation or “mirroring.” Prior evidence shows that mentalizing tasks engage a neural network which includes the temporoparietal junction, superior temporal sulcus, and medial prefrontal cortex. On the other hand, simulation tasks engage the fronto-parietal mirror neuron system (MNS) which includes the inferior frontal gyrus (IFG) and the somotosensory related cortex (SRC). Here, we tested whether neural activity in these two neural networks was related to self-reports of cognitive and affective empathy in daily life. Participants viewed social scenes in which the shift of direction of attention of a character did or did not change the character's mental and emotional state. As expected, the task robustly activated both mentalizing and MNS networks. We found that when detecting the character's change in mental and emotional state...

Rose's Human Nature of Property

Smith, Henry Edward
Fonte: College of William and Mary Publicador: College of William and Mary
Tipo: Artigo de Revista Científica
EN_US
Many social theories claim to have the human being at their center. That has been more a matter of theory than practice in many of those theories. But in the case of Carol Rose’s scholarship on property it could not be more true. In many of her works, Carol develops sophisticated theories about property by focusing in on characters. While they are sometimes humorous and colorful, the characters capture something important about human nature, and Carol, like an older tradition that we could learn a lot from, explores property through the lens of human nature. In it she finds many twists and turns. I will focus on how the characters of the ninny and the scoundrel call for crystals and mud1—bright line rules and vague standards, yes, but quite a bit more than that. In Carol’s view a variety of the tragedy of the commons with crystals and mud leads to endless cycling between crystals and mud.2 At the end I will argue that human nature may also lead to a sort of equilibrium in the law, an equilibrium we could associate with the traditions of law versus equity. But for that to occur we do need some significant degree of moral consensus, upon which we can ground our equitable interventions. This need for moral consensus takes us back to Carol’s insights about human nature and to her humanistic bourgeois view of property based on narrative. Carol points out that famous accounts of property from Locke and Blackstone to Demsetz all involve a view—or views—of human nature.3 All of them ground a picture of property in self-interest...

Endogenous Levels of Circulating Androgens and Risk of Crohn's Disease and Ulcerative Colitis Among Women: A Nested Case–Control Study from the Nurses' Health Study Cohorts

Khalili, Hamed; Ananthakrishnan, Ashwin N.; Konijeti, Gauree G.; Higuchi, Leslie M.; Fuchs, Charles S.; Richter, James M.; Tworoger, Shelley S.; Hankinson, Susan E.; Chan, Andrew T.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
EN_US
Background: Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function. No study has evaluated the association between circulating levels of androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted a nested case–control study of women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and UC were each matched to 2 controls. Prediagnosis plasma levels of dehydroepiandrosterone sulfate, testosterone, and sex hormone–binding globulin were measured. We examined the association of each analyte with risk of CD or UC using conditional logistic regression models. Results: Compared with women in the lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD were 0.86 (95% confidence interval, 0.39–1.90) for women in the second quintile, 0.49 (95% confidence interval, 0.21–1.15) for the third quartile, 0.22 (0.08–0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16–0.99) for the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a consistent association between prediagnostic testosterone and risk of UC (Plinear trend = 0.84). We also did not observe any association between plasma levels of sex hormone–binding globulin or dehydroepiandrosterone sulfate and risk of UC or CD (all Plinear trends > 0.10). Conclusions: Among women...

'SEEDY' (Simulation of Evolutionary and Epidemiological Dynamics): An R Package to Follow Accumulation of Within-Host Mutation in Pathogens

Worby, Colin J.; Read, Timothy D.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
Genome sequencing is an increasingly common component of infectious disease outbreak investigations. However, the relationship between pathogen transmission and observed genetic data is complex, and dependent on several uncertain factors. As such, simulation of pathogen dynamics is an important tool for interpreting observed genomic data in an infectious disease outbreak setting, in order to test hypotheses and to explore the range of outcomes consistent with a given set of parameters. We introduce ‘seedy’, an R package for the simulation of evolutionary and epidemiological dynamics (http://cran.r-project.org/web/packages/seedy/). Our software implements stochastic models for the accumulation of mutations within hosts, as well as individual-level disease transmission. By allowing variables such as the transmission bottleneck size, within-host effective population size and population mixing rates to be specified by the user, our package offers a flexible framework to investigate evolutionary dynamics during disease outbreaks. Furthermore, our software provides theoretical pairwise genetic distance distributions to provide a likelihood of person-to-person transmission based on genomic observations, and using this framework, implements transmission route assessment for genomic data collected during an outbreak. Our open source software provides an accessible platform for users to explore pathogen evolution and outbreak dynamics via simulation...

Limits on information transduction through amplitude and frequency regulation of transcription factor activity

Hansen, Anders S; O'Shea, Erin K
Fonte: eLife Sciences Publications, Ltd Publicador: eLife Sciences Publications, Ltd
Tipo: Artigo de Revista Científica
EN_US
Signaling pathways often transmit multiple signals through a single shared transcription factor (TF) and encode signal information by differentially regulating TF dynamics. However, signal information will be lost unless it can be reliably decoded by downstream genes. To understand the limits on dynamic information transduction, we apply information theory to quantify how much gene expression information the yeast TF Msn2 can transduce to target genes in the amplitude or frequency of its activation dynamics. We find that although the amount of information transmitted by Msn2 to single target genes is limited, information transduction can be increased by modulating promoter cis-elements or by integrating information from multiple genes. By correcting for extrinsic noise, we estimate an upper bound on information transduction. Overall, we find that information transduction through amplitude and frequency regulation of Msn2 is limited to error-free transduction of signal identity, but not signal intensity information. DOI: http://dx.doi.org/10.7554/eLife.06559.001

Abnormal error processing in depressive states: a translational examination in humans and rats

Beard, C; Donahue, R J; Dillon, D G; Van't Veer, A; Webber, C; Lee, J; Barrick, E; Hsu, K J; Foti, D; Carroll, F I; Carlezon Jr, W A; Björgvinsson, T; Pizzagalli, D A
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN_US
Depression has been associated with poor performance following errors, but the clinical implications, response to treatment and neurobiological mechanisms of this post-error behavioral adjustment abnormality remain unclear. To fill this gap in knowledge, we tested depressed patients in a partial hospital setting before and after treatment (cognitive behavior therapy combined with medication) using a flanker task. To evaluate the translational relevance of this metric in rodents, we performed a secondary analysis on existing data from rats tested in the 5-choice serial reaction time task after treatment with corticotropin-releasing factor (CRF), a stress peptide that produces depressive-like signs in rodent models relevant to depression. In addition, to examine the effect of treatment on post-error behavior in rodents, we examined a second cohort of rodents treated with JDTic, a kappa-opioid receptor antagonist that produces antidepressant-like effects in laboratory animals. In depressed patients, baseline post-error accuracy was lower than post-correct accuracy, and, as expected, post-error accuracy improved with treatment. Moreover, baseline post-error accuracy predicted attentional control and rumination (but not depressive symptoms) after treatment. In rats...

Do biologic markers predict cardiovascular end points in diabetic end-stage renal disease? A prospective longitudinal study

Bayliss, George P.; Weinrauch, Larry A.; Gleason, Ray E.; Lee, Annette T.; D'Elia, John A.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN_US
Background: Diabetic patients on hemodialysis are at high risk of death from cardiovascular disease, and research has suggested that various biologic markers of inflammation, oxidative stress and hemostasis may give added value to clinical information for predicting cardiovascular event (CVE)-free survival. This information could be particularly important in evaluating this population for renal transplant, given the scarcity of organs. We hypothesized that in diabetic patients undergoing renal replacement therapy (RRT) these biologic markers would prove useful in predicting event-free follow-up in a prospective study. Methods: One hundred and fifty diabetic (76 type 1, 74 type 2) and 27 non-diabetic stable RRT patients were followed for 0.04–13.69 years for CVE (myocardial infarction, coronary arterial intervention, peripheral arterial bypass or amputation, cerebrovascular accident or carotid artery intervention), cardiac and all-cause mortality. Measured biologic markers of inflammation included the following: Il-6, C reactive protein, fibrinogen; of hemostasis: fibrinogen, plasminogen activator inhibitor (PAI), fibrinolytic activity, von Willebrand factor VII (vWF), platelet-selectin, viscosity and of oxidative stress: advanced glycated end products and antibody to oxidized low-density lipoprotein. For each...

CR6-interacting factor 1 is a key regulator in Aβ-induced mitochondrial disruption and pathogenesis of Alzheimer's disease

Byun, J; Son, S M; Cha, M-Y; Shong, M; Hwang, Y J; Kim, Y; Ryu, H; Moon, M; Kim, K-S; Mook-Jung, I
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN_US
Mitochondrial dysfunction, often characterized by massive fission and other morphological abnormalities, is a well-known risk factor for Alzheimer's disease (AD). One causative mechanism underlying AD-associated mitochondrial dysfunction is thought to be amyloid-β (Aβ), yet the pathways between Aβ and mitochondrial dysfunction remain elusive. In this study, we report that CR6-interacting factor 1 (Crif1), a mitochondrial inner membrane protein, is a key player in Aβ-induced mitochondrial dysfunction. Specifically, we found that Crif1 levels were downregulated in the pathological regions of Tg6799 mice brains, wherein overexpressed Aβ undergoes self-aggregation. Downregulation of Crif1 was similarly observed in human AD brains as well as in SH-SY5Y cells treated with Aβ. In addition, knockdown of Crif1, using RNA interference, induced mitochondrial dysfunction with phenotypes similar to those observed in Aβ-treated cells. Conversely, Crif1 overexpression prevented Aβ-induced mitochondrial dysfunction and cell death. Finally, we show that Aβ-induced downregulation of Crif1 is mediated by enhanced reactive oxygen species (ROS) and ROS-dependent sumoylation of the transcription factor specificity protein 1 (Sp1). These results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying Aβ-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. We propose that Crif1 may serve as a novel therapeutic target in the treatment of AD.

"It's the authors, stupid!"

Suber, Peter
Fonte: Scholarly Publishing and Academic Resources Coalition Publicador: Scholarly Publishing and Academic Resources Coalition
Tipo: Artigo de Revista Científica
EN_US

Germany's DFG adopts an open access policy

Suber, Peter
Fonte: Scholarly Publishing and Academic Resources Coalition Publicador: Scholarly Publishing and Academic Resources Coalition
Tipo: Artigo de Revista Científica
EN_US

Elsevier's new postprint archiving policy, continued

Suber, Peter
Fonte: Scholarly Publishing and Academic Resources Coalition Publicador: Scholarly Publishing and Academic Resources Coalition
Tipo: Artigo de Revista Científica
EN_US

Google's gigantic library project

Suber, Peter
Fonte: Scholarly Publishing and Academic Resources Coalition Publicador: Scholarly Publishing and Academic Resources Coalition
Tipo: Artigo de Revista Científica
EN_US

Optimizing Care for Low Birth Weight Infants in Rural Malawi

Kalanga, Noel
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
The aim of our study was to explore and understand the factors that affect growth of low birth weight (LBW) infants in a rural district of Neno in Malawi in order to optimize their care. We surveyed 64 households of LBW infants born between April and June 2014. We collected quantitative data on socio-demographics and food security, and performed nutrition and development assessments of the LBW infants at six months of age. We also conducted qualitative in-depth interviews with a subset of 10 mothers of the LBW infants and with 3 nurses at postnatal clinics. We then merged the quantitative and qualitative datasets for a final interpretation. At six months of age, LBW infants were more likely to be underweight (mean weight-for-age Z-score -3.01±0.97) or stunted (mean height-for-age Z-score -2.45 ±1.34) than the WHO reference group. The majority (93.8%) of the households had moderate to severe food insecurity. Contributing factors to these poor outcomes included recurrent illness, resource scarcity and lack of social support. Most mothers opted for mixed feeding as a coping mechanism for the LBW infant’s slow growth; this mixed feeding without clean water and proper hygiene, could even worsen the health outcomes of these infants. Structural violence in poor households causes poor health outcomes of LBW infants. The responsibility of caring for LBW infants is so challenging because these children have so many unmet needs. Optimum care can be achieved with a variety of biosocial interventions.

Long-Term Intake of Animal Flesh, Fruits and Vegetables and the Incidence of Hypertension in Three Prospective Cohort Studies

Borgi, Lea
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Vegetarian and vegan diets are associated with a lower prevalence of hypertension when compared with animal-based diets. Small, short-term interventional studies showed that replacing an omnivorous diet with a vegetarian diet lowered blood pressure. The potential mechanisms by which plant-based food intake is linked to a reduced risk of hypertension are not well understood. However, proposed effects include systemic inflammation, endothelial dysfunction, and the activation of the renin-angiotensin system (RAS) among those eating animal-based foods. We propose the VEGIE-BP (VEGetarian Initiative on the Endpoint of Blood Pressure) study, a prospective longitudinal study examining the incidence of hypertension in three large-scale, ongoing prospective cohorts with decades of follow-up: the Nurses’ Health Study 1 (NHS1), the Nurses’ Health Study 2 (NHS2), and the Health Professionals Follow-up Study (HPFS). These cohorts have validated information about health outcomes, as well as longitudinal and repeated measures of diet using detailed food-frequency questionnaires. Biomarkers of inflammation and endothelial function have also been measured on many of these participants, and at several time points in some participants. These cohorts therefore represent a unique resource to analyze the longitudinal associations of vegetarian/vegan diets and specific foods with the incidence of hypertension as well as associations with inflammation and endothelial dysfunction. In addition...

Stem Cell-Based Modeling in Pain and ALS

Wainger, Brian
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Translational research in neurological disorders has largely focused on single or oligo gene rodent models whose value in understanding human disease may be limited. Advances in stem cell technology allow disease modeling using human neurons derived from patients. We have explored the use of derived neuronal cell types in modeling pain and motor neuron disease. In the first case, we use the technique of lineage reprogramming to transdifferentiate human fibroblasts into neurons by Marius Wernig and colleagues. We find that we can derive nociceptor neurons from mouse and human fibroblasts using a group of five transcription factors. We show how the derived nociceptor neurons may be used to model disease pathophysiology with the future goal of performing phenotype-based drug screens. In the second case, we take advantage of existing techniques for differentiating motor neurons from ALS patient iPSCs. We use stem cell modeling to explore physiological differences between ALS and healthy control-derived motor neurons, and we show how iPSC-based phenotypes can be used as platforms to identify and evaluate therapeutic candidates.

Understanding Barriers to Neonatal Resuscitation in a Hospital in Haiti

Wagner, Ariel
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
BACKGROUND: Neonatal mortality is a major problem in developing countries, accounting for 41% of child mortality. Approximately one quarter of these deaths are attributed to birth asphyxia. Although estimates suggest that 99% of asphyxia-related deaths can be prevented with neonatal resuscitation, in many settings, interventions to improve resuscitation have not led to decreases in mortality. OBJECTIVES: This study aimed to develop an understanding of neonatal resuscitation practices at a hospital in Haiti. Specific objectives were: to identify current resuscitation practices at the time of delivery; to characterize provider experiences with newborn care and resuscitation; and to identify perceived barriers to effective resuscitation. METHODS: This mixed methods study collected data through delivery observations and semi-structured individual interviews with health care providers. RESULTS: Fifty-one (32.9%) of the 155 newborns in this study were not breathing at birth. Of these, 45 (88.2%) were successfully resuscitated, 11.8% by drying and stimulation, 19.6% by stimulation and airway clearing, 39.2% by a combination of drying, stimulation, and airway clearing, and 17.6% by bag-mask ventilation with or without chest compressions. Six of the newborns (11.8%) died. The average time to newborn assessment for all deliveries was 16 seconds...

Degradation of Mnemonic Networks in Aging and Alzheimer’s Disease

Chhatwal, Jasmeer
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Functional connectivity MRI (fcMRI) is a non-invasive method to assess the integrity of anatomically distributed neural networks underlying complex behaviors. In Alzheimer’s disease (AD), fcMRI of the default mode network (DMN) has shown great promise as a biomarker in clinical and basic research studies, as (1) profound decreases in DMN fcMRI are seen in prodromal and clinically evident AD and (2) the DMN is among the sites of early amyloid deposition in AD. However, using fcMRI as an early AD biomarker is limited by the overlapping changes in connectivity seen in normal aging, which, in turn, limits the identification of early AD subjects to enroll in clinical trials. To address this limitation, we propose a series of studies that use fcMRI to disambiguate normal aging from early AD by focusing on the pattern of degeneration across six well-described cortical networks in two unique subject populations. The central hypothesis of these studies is that early AD and aging will show distinct patterns of network degradation, with preferential degradation of cognitive networks (especially the Default Mode and Attention Networks) in early AD as compared to aging. We test this hypothesis by comparing young and old subjects with and without evidence of AD pathology...

Electrical Impedance Myography (EIM) and Quantitative Ultrasonography (QUS) Measurements of the Tongue: Biomarkers of Bulbar Dysfunction

McIlduff, Courtney
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Many neurological disorders are associated with speech and swallowing abnormalities. In turn, oropharyngeal dysfunction can negatively impact quality of life and survival. Reliable tools that quantify underlying motor deficits are needed for use in clinical care and therapeutic trials. As painless, non-invasive techniques, electrical impedance myography (EIM) and quantitative ultrasonography (QUS) are well-suited to provide biomarker data. Both of these user-friendly methods can provide sensitive indicators of disease status when applied to the limbs; existing work suggests that the examination of orofacial muscles could add valuable information. This document explores the role of EIM and QUS in evaluating tongue health and bulbar dysfunction in patients with neuromuscular conditions.

The Society for Vascular Surgery’s Objective Performance Goals for Lower Extremity Revascularization Are Not Generalizable to Many Open Surgical Bypass Patients Encountered in Contemporary Surgical Practice

Saraidaridis, Julia T.
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Objective: In 2009, the Society for Vascular Surgery established objective performance goals (OPG) for lower extremity bypass (LEB) in patients with critical limb ischemia (CLI) based on pooled data from previously performed, prospective studies in an effort to provide a benchmark and historical control for future trials. However, patients with prosthetic conduit and end stage renal disease (ESRD) were excluded from this cohort. In contemporary practice, many patients do not meet the criteria for SVS OPG inclusion, making generalization of the SVS OPG difficult. The goal of this study was to establish safety and efficacy measures for patients who were excluded from the original SVS OPG analysis. Methods: All patients who underwent LEB for CLI in the Vascular Study Group of New England (VSGNE) from 2003-2013 were identified. Patients were stratified into OPG eligible and non-OPG cohorts. Outcomes included 30-day Major Adverse Limb Event (MALE), 30-day Major Adverse Cardiovascular Event (MACE), 1-year survival, and 1-year freedom from amputation. Using the SVS OPG methodology, new performance goals were created for the non-OPG eligible patients. Results: 3609 patients were identified: 2360 (65%) OPG versus 1249 (35%) non-OPG and overall results were stratified as a function of OPG status. The 30-day MALE was 5.0% (5.5% non-OPG versus 4.4% OPG; p=0.34)...

Longitudinal Characterization of the FTD-ALS Spectrum

Ratti, Elena
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
EN
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are heterogeneous neurodegenerative diseases that, despite presenting divergent clinical features, can occur within the same person. Based on shared genetics and pathology, characterizing FTD-ALS with clinical and quantitative imaging measures over time may highlight patterns of disease progression and specific brain system vulnerabilities, leading to needed biomarkers development. We propose to build, characterize and compare concurrent FTD-ALS, ALS and FTD cohorts with a prospective observational cohort study performed at Massachusetts General Hospital, including clinical and MRI based imaging measures specific to both ALS and FTD. We will perform quantitative cortical thickness and sub-cortical structures analysis, white matter anatomical and functional integrity evaluations, correlations between anatomical and clinical measures, both within patient and inter-patient populations. To date, there are no longitudinal studies or quantitative cortical thickness evaluations across the entire FTD-ALS continuum. Our longitudinal comprehensive and specialized assessments will lead to the development of a unique dataset evaluating the full FTD-ALS spectrum with standardized measures in a multidisciplinary approach. This will provide the basis for further FTD-ALS research and it will contribute to the development of quantitative biomarkers of disease and disease progression across clinically heterogeneous diseases...