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Recent documents in eScholarship@UMMS
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Sequence Alignment and Homology Search with BLAST and ClustalW

Sun, 02/12/2017 - 5:06pm

This protocol illustrates the steps of searching a sequence database with BLAST, which in essence performs pairwise alignment between the query sequence and each target sequence in the database. Steps for performing multiple sequence alignments with ClustalW are then described. Argonaute 2 (Ago2) is an essential component for small interfering RNA (siRNA)-directed RNA interference (RNAi) in fruit flies. This protocol uses Ago2 to demonstrate how to search for all Ago2 paralogs in the fly proteome using BLAST and to obtain a multiple sequence alignment of these sequences with ClustalW.

Visualizing Genomic Annotations with the UCSC Genome Browser

Sun, 02/12/2017 - 5:06pm

Genomic data and annotations are rapidly accumulating in databases such as the UCSC Genome Browser, NCBI, and Ensembl. Given the massive scale of these genomic databases, it is important to be able to easily retrieve known data and annotations of a specified genomic locus. For example, for a newly identified cis-regulatory element bound by a transcription factor, questions that immediately come to mind include whether the element is near a transcriptional start site and, if so, the name of the corresponding gene, and whether the histones or DNA at the locus are modified. The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. This protocol describes how to use the UCSC Genome Browser to visualize selected tracks at specified genomic regions, download the data and annotations for further analysis, and retrieve multiple sequence alignments and their conservation scores.

Sequence Alignment and Homology Search

Sun, 02/12/2017 - 5:06pm

Bioinformatics was brought into the spotlight in the late 1990s through the Human Genome Project. With the rapid accumulation of completed genomes, it was soon realized that for the vast majority of the newly identified genes and other functional regions of the genomes there were no other biological data. One way of inferring biological function is through homology: Because homologous genes have a common evolutionary descent, they are likely to have the same biological function. A large number of bioinformatics tools have been designed for rapidly and accurately comparing sequences of genes or proteins, comparing gene sequences with genomes, and comparing genomes. Two widely used tools for sequence alignment and homology searches, BLAST and ClustalW, are introduced here.

A generalized framework for computational design and mutational scanning of T-cell receptor binding interfaces

Sun, 02/12/2017 - 5:06pm

T-cell receptors (TCRs) have emerged as a new class of therapeutics, most prominently for cancer where they are the key components of new cellular therapies as well as soluble biologics. Many studies have generated high affinity TCRs in order to enhance sensitivity. Recent outcomes, however, have suggested that fine manipulation of TCR binding, with an emphasis on specificity may be more valuable than large affinity increments. Structure-guided design is ideally suited for this role, and here we studied the generality of structure-guided design as applied to TCRs. We found that a previous approach, which successfully optimized the binding of a therapeutic TCR, had poor accuracy when applied to a broader set of TCR interfaces. We thus sought to develop a more general purpose TCR design framework. After assembling a large dataset of experimental data spanning multiple interfaces, we trained a new scoring function that accounted for unique features of each interface. Together with other improvements, such as explicit inclusion of molecular flexibility, this permitted the design new affinity-enhancing mutations in multiple TCRs, including those not used in training. Our approach also captured the impacts of mutations and substitutions in the peptide/MHC ligand, and recapitulated recent findings regarding TCR specificity, indicating utility in more general mutational scanning of TCR-pMHC interfaces.

Genome-wide CRISPR Screen Identifies Regulators of MAPK as Suppressors of Liver Tumors in Mice

Sun, 02/12/2017 - 5:06pm

BACKGROUND and AIMS: It has been a challenge to identify liver tumor suppressors or oncogenes due to the genetic heterogeneity of these tumors. We performed a genome-wide screen to identify suppressors of liver tumor formation in mice, using CRISPR-mediated genome editing.

METHODS: We performed a genome-wide CRISPR/Cas9-based knockout screen of P53-null mouse embryonic liver progenitor cells that overexpressed MYC. We infected p53-/-;Myc;Cas9 hepatocytes with the mGeCKOa lentiviral library of 67,000 single-guide RNAs (sgRNAs), targeting 20,611 mouse genes, and transplanted the transduced cells subcutaneously into nude mice. Within 1 month, all the mice that received the sgRNA library developed subcutaneous tumors. We performed high-throughput sequencing of tumor DNA and identified sgRNAs increased at least 8-fold compared to the initial cell pool. To validate the top 10 candidate tumor suppressors from this screen, we collected data from patients with hepatocellular carcinoma (HCC) using the Cancer Genome Atlas and COSMIC databases. We used CRISPR to inactivate candidate tumor suppressor genes in p53-/-;Myc;Cas9 cells and transplanted them subcutaneously into nude mice; tumor formation was monitored and tumors were analyzed by histology and immunohistochemistry. Mice with liver-specific disruption of p53 were given hydrodynamic tail-vein injections of plasmids encoding Myc and sgRNA/Cas9 designed to disrupt candidate tumor suppressors; growth of tumors and metastases was monitored. We compared gene expression profiles of liver cells with vs without tumor suppressor gene disrupted by sgRNA/Cas9. Genes found to be upregulated following tumor suppressor loss were examined in liver cancer cell lines; their expression was knocked down using small hairpin RNAs, and tumor growth was examined in nude mice. Effects of the MEK inhibitors AZD6244, U0126, and trametinib, or the multi-kinase inhibitor sorafenib, were examined in human and mouse HCC cell lines.

RESULTS: We identified 4 candidate liver tumor suppressor genes not previously associated with liver cancer (Nf1, Plxnb1, Flrt2, and B9d1). CRISPR-mediated knockout of Nf1, a negative regulator of RAS, accelerated liver tumor formation in mice. Loss of Nf1 or activation of RAS upregulated the liver progenitor cell markers HMGA2 and SOX9. RAS pathway inhibitors suppressed the activation of the Hmga2 and Sox9 genes that resulted from loss of Nf1 or oncogenic activation of RAS. Knockdown of HMGA2 delayed formation of xenograft tumors from cells that expressed oncogenic RAS. In human HCCs, low levels of NF1 mRNA or high levels of HMGA2 mRNA were associated with shorter patient survival time. Liver cancer cells with inactivation of Plxnb1, Flrt2, and B9d1 formed more tumors in mice and had increased levels of MAPK phosphorylation.

CONCLUSIONS: Using a CRISPR-based strategy, we identified Nf1, Plxnb1, Flrt2, and B9d1 as suppressors of liver tumor formation. We validated the observation that RAS signaling, via MAPK, contributes to formation of liver tumors in mice. We associated decreased levels of NF1 and increased levels of its downstream protein HMGA2 with survival times of patients with HCC. Strategies to inhibit or reduce HMGA2 might be developed to treat patients with liver cancer.

Mapping Billions of Short Reads to a Reference Genome

Sun, 02/12/2017 - 5:06pm

Rapid development and commercialization of instruments that can accurately, rapidly, and cheaply sequence billions of DNA bases is revolutionizing molecular biology and medicine. Because a reference genome is usually available, the first bioinformatics challenge presented by the new generation of high-throughput sequencers is the genome mapping problem, where each read is mapped to a reference genome to reveal its location(s). An introduction to mapping algorithms, as well as factors that influence their results, is provided here.

CAF-1 p150 and Ki-67 Regulate Nuclear Structure Throughout the Human Cell Cycle

Fri, 02/10/2017 - 2:17pm

The three-dimensional organization of the human genome is non-random in interphase cells. Heterochromatin is highly clustered at the nuclear periphery, adjacent to nucleoli, and near centromeres. These localizations are reshuffled during mitosis when the chromosomes are condensed, nucleoli disassembled, and the nuclear envelope broken down. After cytokinesis, heterochromatin is re-localized to the domains described above. However, the mechanisms by which this localization is coordinated are not well understood. This dissertation will present evidence showing that both CAF-1 p150 and Ki-67 regulate nuclear structure throughout the human cell cycle.

Chromatin Assembly Factor 1 (CAF-1) is a highly conserved three-subunit protein complex which deposits histones (H3/H4)2 heterotetramers onto replicating DNA during S-phase of the cell cycle. The N-terminal domain of the largest subunit of CAF-1 (p150N) is dispensable for histone deposition, and instead regulates the localization of specific loci (Nucleolar-Associated Domains, or “NADs”) and several proteins to the nucleolus during interphase. One of the proteins regulated by p150N is Ki-67, a protein widely used as a clinical marker of cellular proliferation. Depletion of Ki-67 decreases the association of NADs to the nucleolus in a manner similar to that of p150. Ki-67 is also a fundamental component of the perichromosomal layer (PCL), a sheath of proteins that surrounds all condensed chromosomes during mitosis. A subset of p150 localizes to the PCL during mitosis, and depletion of p150 disrupts Ki-67 localization to the PCL. This activity was mapped to the Sumoylation Interacting Motif (SIM) within p150N, which is also required for the localization of NADs and Ki-67 to the nucleolus during interphase. Together, these studies indicate that p150N coordinates the three-dimensional arrangement of both interphase and mitotic chromosomes via Ki-67.

Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles in Cardiac Progenitor Cells

Fri, 02/10/2017 - 2:17pm

Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational lethality. In primary heart field progenitors, Hdac3 interacts with, deacetylates, and functionally suppresses transcription factor Tbx5. Furthermore, a disease-associated Tbx5 mutation disrupts this interaction, rendering Tbx5 hyperacetylated and hyperactive. By contrast, deletion of Hdac3 in second heart field progenitors bypasses these defects, instead causing malformations in the outflow tract and semilunar valves, with lethality prior to birth. Affected semilunar valves and outflow tract vessels exhibit extracellular matrix and EndMT defects and activation of the Tgfβ1 signaling pathway. In normal second heart field development, Hdac3 represses Tgfβ1 transcription, independent of its deacetylase activity, by recruiting the PRC2 methyltransferase complex to methylate the Tgfβ1 promoter. Importantly, knockouts of Hdac3 in differentiated cardiac cells do not fully recapitulate the progenitor-specific knockout phenotypes. These results illustrate spatiotemporal roles of Hdac3, both deacetylase-dependent and deacetylase-independent, in cardiac development, suggesting that dysregulation of Hdac3 in cardiac progenitor cells could be a contributing factor in congenital heart disease pathogenesis.

A Translational Pathway for Recombinant Adeno-Associated Virus Human Gene Therapy: From Target Identification and Animal Modeling of the Disease to Non-Human Primate and Human Studies

Fri, 02/10/2017 - 2:16pm

Many steps go into developing a clinical viral gene therapy. The course starts with appropriate disease selection and moves through the many hurdles of in-vitro testing, animal model validation and proof-of-concept studies, all the way through pre-clinical large animal studies. In this thesis, I propose to outline the process of developing a translation pathway for a gene therapy using recombinant adeno-associated virus (rAAV). I will expand on this outline using data that I have generated during the course of my Ph.D. that ranges from animal model validation all the way through pre-clinical vector stability studies. Two disease models will be discussed throughout this thesis, Cockayne Syndrome (CS) and Alpha-1 Antitrypsin Deficiency (AATD). Cockayne Syndrome is a rare autosomal recessive genetic disorder involving mutations in either the CSA or CSB gene, leading to defects in DNA repair. Clinically this presents as progressive degeneration of the central nervous system, retina, cardiovascular system, and cochlea, which leads to mental retardation, post-natal growth defects, ocular abnormalities, and shortened life expectancy. Alpha-1 antitrypsin is a serine protease inhibitor largely produced in the liver that mainly functions to inhibit neutrophil elastase within the lung. AATD leads to an increased risk of emphysema, with shortened life expectancy, and also results in accumulations of mutant AAT polymers in the liver, sometimes leading to liver failure. Using these two disease models I will outline the upstream and downstream pre-clinical work as well as the transition to clinical trials of a rAAV based gene therapy.

Data from: Predictors of Lack of Partial Clinical Remission in New-onset Pediatric Type 1 Diabetes

Fri, 02/10/2017 - 11:00am

This dataset is the primary data source for a manuscript submitted for publication.

Political Efficacy and Political Participation of Nurse Practitioners: A Dissertation

Wed, 02/08/2017 - 12:55pm

In many states, outdated rules and regulations restrict nurse practitioners (NPs) from practicing to their full potential, often limiting patients’ access to primary care. Modernizing NP state scope of practice laws and allowing patients greater access to NPs services is a priority. Unlike other professions, nurse practitioners have been unable to consistently influence legislative changes to health policy. This study examined the political efficacy and participation of nurse practitioners in the United States today (N=632). A descriptive cross sectional design, in conjunction with a political efficacy framework, evaluated nurse practitioners’ participation in political activities and their internal and external political efficacy. Increased internal political efficacy was significantly (p < 0.001) associated with NPs who were older, had specific health policy education, and have been mentored in health policy. Our findings show that NPs vote at consistently higher rates (94%) than the general population and almost 50% report contacting legislators via mail/email/phone. As a group however, NPs report limited participation in other political activities, especially grassroots efforts. These findings hold significant implications for the profession as we strive to make policy changes across the country. It is important that educators assess our current methods of educating NPs about politics and health policy. Professional organizations and policy makers must reexamine outreach and strategies to inspire greater grassroots engagement of NPs.

Macrocognition in the Health Care Built Environment (m-HCBE): A Focused Ethnographic Study of 'Neighborhoods' in a Pediatric Intensive Care Unit: A Dissertation

Wed, 02/08/2017 - 12:55pm

Objectives: The objectives of this research were to describe the interactions (formal and informal) in which macrocognitive functions occur and their location on a pediatric intensive care unit (PICU); describe challenges and facilitators of macrocognition using three constructs of space syntax (openness, connectivity, and visibility); and analyze the health care built environment (HCBE) using those constructs to explicate influences on macrocognition.

Background: In high reliability, complex industries, macrocognition is an approach to develop new knowledge among interprofessional team members. Although macrocognitive functions have been analyzed in multiple health care settings, the effect of the HCBE on those functions has not been directly studied. The theoretical framework, “Macrocognition in the Health Care Built Environment” (m-HCBE) addresses this relationship.

Methods: A focused ethnographic study was conducted, including observation and focus groups. Architectural drawing files used to create distance matrices and isovist field view analyses were compared to panoramic photographs and ethnographic data.

Results: Neighborhoods comprised of corner configurations with maximized visibility enhanced team interactions as well as observation of patients, offering the greatest opportunity for informal situated macrocognitive interactions (SMIs).

Conclusions: Results from this study support the intricate link between macrocognitive interactions and space syntax constructs within the HCBE. These findings help to advance the m-HCBE theory for improving physical space by designing new spaces or refining existing spaces, or for adapting IPT practices to maximize formal and informal SMI opportunities; this lays the groundwork for future research to improve safety and quality for patient and family care.

The DREAMers Study: Undocumented College Students and Their Mental Health Needs

Tue, 02/07/2017 - 3:36pm

Undocumented college students face several barriers that may place them at high risk of poor mental health. Despite growing up and receiving primary and secondary (K-12) education in the U.S., many undocumented young adults cannot legally work, vote or drive in most states. Their illegal status interferes with their ability to accumulate relevant/ practical work experience leading to the inability to develop the necessary job skills before graduating high school, which can limit their employment opportunities.

Ipsilateral Lower Limb Weakness After Sarcoma Treatment: A Case Report

Mon, 02/06/2017 - 12:25pm

Case Diagnosis: Our patient experienced worsening left foot neuropathy following chemotherapy and radiation treatment for sarcoma.

Case Description: A 24-year-old man underwent local resection of a 12cm x 8cm x 14.5cm rhabdomyosarcoma in the left vastus lateralis. Then, he was treated with vincristine for 40 weeks and radiation to the left lateral thigh with a maximum dose of 50.4 Gy. The sciatic nerve was outside the target area and received a lower dose. While undergoing chemotherapy, the patient experienced bilateral dysesthesias in his fingertips and feet. He had no history of neuropathy prior to treatment. After chemotherapy was completed, these symptoms subsided in all extremities except the left foot, which developed atraumatic plantar flexion and dorsiflexion weakness, great toe extensor and flexor weakness, decreased sensation in the distal left toe to the metatarsal. Electromyography and needle conduction studies demonstrated left worse than right polyneuropathy mainly affecting the tibial and peroneal motor nerves. There was no clear evidence of a single nerve compressive lesion and repeat scans of the thigh showed no new lesion. Given the presence of milder nerve abnormalities on the right in addition to left sided weakness, the cause is likely multifactorial and temporally related to cancer treatments.

Discussions: Persistent or worsening features may appear in patients who received vincristine despite termination of treatment. The pattern is typically sensorimotor; however, this patient demonstrates mainly motor abnormalities. The left worse than right pattern could suggest radiation-induced neuropathy, but no myokymic potentials were seen. Myokymic potentials are common in radiation neuropathy, although their absence does not rule it out. Treatment included physical therapy, gabapentin, and an ankle foot orthosis.

Conclusions: Fourteen months after completing radiation and seven months after completing chemotherapy (seven months after symptom onset), the patient’s symptoms are markedly improved. This case demonstrates that neuropathy after treatment in sarcoma patients may be multifactorial.

Total Joint Replacement Prehabilitation: A Feasibility Study

Mon, 02/06/2017 - 12:25pm

Objectives: Pre-operative physical therapy has been shown to reduce post-acute care service utilization. Shifting rehabilitation to the presurgical period, referred to as prehabilitation, could result in reduced recovery time and cost. Limited access to physical therapy may prevent patients from achieving the benefits, and a standard set of independent exercises may be an alternative. We aim to assess the feasibility of an independent exercise program as a pre-surgical intervention for total hip and knee replacement.

Design: Participants were taught two exercises for hip or knee arthritis at least one week prior to surgery and instructed to perform them independently at home. Subjects were contacted three days to one month post-operatively and surveyed about discharge, frequency of exercise, and living status of alone or with others. No adverse effects were reported. Additional information was collected from the subjects’chart including age, BMI, and sex. Discharge outcomes were compared with pre-existing independent factors using univariate and multivariate analyses.

Results: A total of 80 subjects were followed with a home discharge rate of 78.75%. Univariate analyses showed that the presence of other people in the home showed a slight, but non-significant, association with differences of discharge destination. 82.1%-83.3% of patients who live with others were discharged home versus 57.1% of patients living alone (LR chi-square: 3.84, p=0.15). Multivariate analyses showed a slight, but non-significant, association between frequency of prehabilitation and discharge destination (OR=1.212; 95% CI, 0.960-1.530). BMI showed no associated difference in discharge destination.

Conclusions: Increased frequency of prehabilitation and presence of others at home showed slight associations with increased discharges to home, but were non-significant. Increased exposure to prehabilitation (duration times frequency) trends toward more frequent home discharge. Independently performed prehabilitation may be offered as an alternative pre-surgical intervention with likely little to no adverse effect. Larger numbers are needed to determine likelihood of discharge home.

Two Cases of Lyme Arthritis in Winter In New England: A Case Series

Mon, 02/06/2017 - 12:25pm

Case Diagnosis: Lyme Arthritis

Case Description: Patient 1 is a 26 year old male who presented in March with severe right knee pain and swelling for two weeks. He had a similar episode a month prior, but it resolved. The second episode progressed with pain from knee to foot and numbness on top of the foot. He had no known history of tick bites, travel, or trauma, but endorsed contact with a dog. On physical exam, he had a right knee effusion with limited ROM, diffuse joint line tenderness, positive McMurray’s, and pain with ligamentous testing. Synovial fluid of the joint showed WBC count 44,467 and was positive for Lyme. He was treated with doxycycline. MRI findings were limited to ACL laxity and inflammation.

Patient 2 is a 24 year old male who presented in December with progressive right knee and calf pain for one week. He had been fishing in the woods a few weeks prior with no trauma. Joint aspiration showed a positive Lyme PCR and WBC count 37,520, and he was treated with doxycycline. Aspiration was repeated for recurrent effusion, and an MRI was done due to persistent pain. MRI showed bone contusion, ACL laxity, and inflammation.

Discussions: Lyme disease is transmitted by Ixodes scapularis ticks, which appear in late spring and early summer; however,Lyme arthritis may occur during any season. Ticks infected with the spirochete B. burgdorferi are primarily found in the Northeastern and upper Midwestern US. B. burgdorferi strains of Lyme often disseminate to joints, tendons, or bursae early in infection.Lyme arthritis presents later, with an adaptive immune response that results in spirochetal killing.

Conclusions: Lyme arthritis can present at any time of year, and clinical suspicion in endemic regions should remain high even without a known history of tick exposure or erythema migrans rash.

Fresh Start, a postpartum weight loss intervention for diverse low-income women: design and methods for a randomized clinical trial

Thu, 02/02/2017 - 2:44pm

BACKGROUND: Overweight and obesity are prevalent among young women and are greater among minority and low-income women. The postpartum period is critical in women's weight trajectories as many women do not lose their pregnancy weight, and others lose some and then plateau or experience weight gain. Excess weight puts women at greater risk of chronic disease and thus weight loss in the postpartum period may be key to the long-term health of young women. This paper describes the design and methods of a randomized clinical trial of Fresh Start, an innovative narrative-based group intervention aimed at promoting postpartum weight loss among low-income, diverse women.

METHODS/DESIGN: Study participants were recruited from the five sites of the Women, Infants and Children (WIC) program in central Massachusetts. Participants were English-speaking, age > /= 18 years, 6 weeks to 6 months postpartum, with a body mass index (BMI) > /= 27 kg/m(2). The Fresh Start postpartum weight loss intervention, adapted from the Diabetes Prevention Program (DPP) in collaboration with WIC staff and clients, consisted of an 8-week group-based curriculum followed by nine monthly telephone calls. It included a narrative component (i.e., storytelling), group discussions, print materials and access to exercise facilities. The study is a two-arm randomized controlled trial. The control condition included print materials and access to exercise facilities. In-person assessments were conducted at baseline and at 6 and 12 months following the eight-week intervention phase.

DISCUSSION: The Fresh Start intervention translated key elements of an evidence-based weight loss protocol into a format that is hypothesized to be relevant, acceptable and effective for the target audience of low-SES postpartum women. This novel intervention was developed in collaboration with WIC to be sustainable within the context of its clinics, which reach approximately 9 million individuals per year across the U.S. via 10,000 clinics. TRIAL

REGISTRATION: NCT02176915. Registered 25 June 2014.

Longitudinal changes in neurodevelopmental outcomes between 18 and 36 months in children with prenatal triptan exposure: findings from the Norwegian Mother and Child Cohort Study

Thu, 02/02/2017 - 2:44pm

OBJECTIVE: This study sought to determine whether changes in neurodevelopmental outcomes between 18 and 36 months of age were associated with prenatal exposure to triptan medications, a class of 5-HT receptor agonists used in the treatment of migraine.

METHOD: Using data from the Norwegian Mother and Child Cohort Study, a prospective birth cohort that includes nearly 40% of all pregnancies in Norway from 1999 to 2008, we identified 50 469 mother-child dyads who met inclusion criteria and were present for at least one follow-up assessment at 18 or 36 months postpartum. Neurodevelopment was assessed using the Child Behaviour Checklist, the Emotionality, Activity, and Shyness Questionnaire, and the Ages and Stages Questionnaire. We used generalised estimating equations to evaluate change from 18 to 36 months for children prenatally exposed to triptans, relative to contrast groups, and used marginal structural models with inverse probability of treatment and censoring weights to address time-varying exposure and confounding as well as loss to follow-up.

RESULTS: Among eligible participants (n=50 469), 1.0% used a triptan during pregnancy, 2.0% used triptans prior to pregnancy only, 8.0% reported migraine without triptan use and 89.0% had no history of migraine. Children with prenatal triptan exposure had greater increases in emotionality (r-RR 2.18, 95% CI 1.03 to 4.53) and activity problems (r-RR 1.70, 95% CI 1.02 to 2.8) compared to children born to mothers who discontinued triptan use prior to pregnancy.

CONCLUSION: Prenatal triptan exposure was associated with changes over time in externalising-type behaviours such as emotionality and activity, but not with internalising-type behaviours.

Neighborhood environment correlates of physical activity and sedentary behavior among Latino adults in Massachusetts

Thu, 02/02/2017 - 2:44pm

BACKGROUND: U.S. Latinos experience high rates of cardio-metabolic diseases and have high rates of physical inactivity and sedentary behavior. Understanding the environmental factors associated with physical activity and sedentary behaviors among Latinos could inform future interventions. The purpose of this study is to explore the neighborhood environment correlates of physical activity and sedentary behavior in a sample of U.S. Latino adults.

METHODS: Cross-sectional study of 602 Latino adults in Lawrence, MA. Survey assessments of physical activity, sedentary behavior, and neighborhood environment were verbally administered. The neighborhood environment scale assessed violence, safety, aesthetic quality, walkability, availability of healthy foods, social cohesion, and activities with neighbors.

RESULTS: After controlling forage, gender, education, body mass index (BMI), and smoking status, two variables were associated with the outcomes of interest. Living in more walkable neighborhoods was associated with an increased likelihood of engaging in adequate levels of physical activity ( > 150 min per week, as recommended by the American College of Sports Medicine (ACSM)) (OR = 1.403, p = .018); and greater frequency of activities with neighbors was associated with greater sedentary behavior (beta = .072, p = .05).

CONCLUSIONS: There were different neighborhood environment correlates of physical activity and sedentary behavior in this Latino community. Focusing on a greater understanding of the distinct social and physical environmental correlates of physical activity and sedentary behavior may provide important insights for reducing CVD risk and health disparities among Latinos.

Multimodal Learning and Intelligent Prediction of Symptom Development in Individual Parkinson's Patients

Thu, 02/02/2017 - 2:44pm

We still do not know how the brain and its computations are affected by nerve cell deaths and their compensatory learning processes, as these develop in neurodegenerative diseases (ND). Compensatory learning processes are ND symptoms usually observed at a point when the disease has already affected large parts of the brain. We can register symptoms of ND such as motor and/or mental disorders (dementias) and even provide symptomatic relief, though the structural effects of these are in most cases not yet understood. It is very important to obtain early diagnosis, which can provide several years in which we can monitor and partly compensate for the disease's symptoms, with the help of various therapies. In the case of Parkinson's disease (PD), in addition to classical neurological tests, measurements of eye movements are diagnostic. We have performed measurements of latency, amplitude, and duration in reflexive saccades (RS) of PD patients. We have compared the results of our measurement-based diagnoses with standard neurological ones. The purpose of our work was to classify how condition attributes predict the neurologist's diagnosis. For n = 10 patients, the patient age and parameters based on RS gave a global accuracy in predictions of neurological symptoms in individual patients of about 80%. Further, by adding three attributes partly related to patient 'well-being' scores, our prediction accuracies increased to 90%. Our predictive algorithms use rough set theory, which we have compared with other classifiers such as Naive Bayes, Decision Trees/Tables, and Random Forests (implemented in KNIME/WEKA). We have demonstrated that RS are powerful biomarkers for assessment of symptom progression in PD.