Digital Commons Network^™

Creation And Internal Validation Of A Clinical Predictive Model For Fluconazole Resistance In Patients With Candida Bloodstream Infection, Adriana M Rauseo, Margaret A Olsen, Dustin Stwalley, Patrick B Mazi, Lindsey Larson, William G Powderly, Andrej Spec

2020-Current year OA Pubs

BACKGROUND: Fluconazole is recommended as first-line therapy for candidemia when risk of fluconazole resistance (fluc-R) is low. Lack of methods to estimate resistance risk results in extended use of echinocandins and prolonged hospitalization. This study aimed to develop a clinical predictive model to identify patients at low risk for fluc-R where initial or early step-down fluconazole would be appropriate.

METHODS: Retrospective analysis of hospitalized adult patients with positive blood culture for

RESULTS: We identified 539 adults with candidemia and 72

CONCLUSIONS: This model is a potential tool for identifying patients at low risk for fluc-R candidemia to receive first-line or …

Pregnancy Outcomes Related To The Treatment Of Sarcomas With Anthracyclines And/Or Ifosfamide During Pregnancy, Devon Miller, John A Livingston, Yeonhee Park, Kristi Posey, Sonia Godbole, Keith Skubitz, Steven I Robinson, Mark Agulnik, Lara E Davis, Brian A Van Tine, Angela C Hirbe, Amanda Parkes

2020-Current year OA Pubs

BACKGROUND: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas.

PATIENTS AND METHODS: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank-sum test compared two independent samples.

RESULTS: We identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and …

Adolescent And Young Adult Preferences For Financial Incentives To Support Adherence To Antiretroviral Therapy In Kenya: A Mixed Methods Study, Ingrid Eshun-Wilson, Eliud Akama, Fridah Adhiambo, Zachary Kwena, Bertha Oketch, Sarah Obatsa, Sarah Iguna, Jayne L Kulzer, James Nyanga, Everlyne Nyandieka, Ally Scheve, Elvin H Geng, Elizabeth A Bukusi, Lisa Abuogi

2020-Current year OA Pubs

INTRODUCTION: To develop a patient-centred financial incentive delivery strategy to improve antiretroviral treatment adherence in adolescents and young adults (AYA) living with HIV in Kisumu, Kenya, we conducted a mixed methods study exploring preferences.

METHODS: A discrete choice experiment (DCE) and focus group discussion (FGD) were conducted simultaneously to identify preferences for five incentive delivery strategy features: value, eligibility, recipient, format and disbursement frequency. We used consecutive sampling to recruit AYA (14-24 years) living with HIV attending three health facilities in Kisumu, Kenya. We calculated mean preferences, willingness to trade, latent class membership and predictors of latent class membership. The …

Remote Symptom Monitoring Of Patients With Cancer Undergoing Radiation Therapy, Ryan Wahidi, Rachel Mintz, Temitope Agabalogun, Lindsey Mayer, Shahed Badiyan, Matthew B. Spraker

2020-Current year OA Pubs

The goal of the study was to develop and test an automated short message service (SMS) and web service platform using CareSignal for remote symptom monitoring in a diverse population of patients with cancer. Twenty-eight patients with cancer undergoing radiotherapy were recruited at the start of their treatment regimen. Patients received a weekly SMS symptom survey to assess the severity of the side effects they experienced from treatment. An assessment of patient perceptions of the system in terms of patient-provider communication, feasibility, and overall satisfaction was conducted, finding overall good compliance in a sick patient population and patient willingness to …

Coronavirus Disease 2019 (Covid-19) Vaccination Preparedness Policies In Us Hospitals, Susan E Beekmann, Hilary M Babcock, Mark S Rasnake, Thomas R Talbot, Philip M Polgreen

2020-Current year OA Pubs

We surveyed infectious disease specialists about early coronavirus disease 2019 (COVID-19) vaccination preparedness. Almost all responding institutions rated their facility's preparedness plan as either excellent or adequate. Vaccine hesitancy and concern about adverse reactions were the most commonly anticipated barriers to COVID-19 vaccination. Only 60% believed that COVID-19 vaccination should be mandatory.

First-In-Human Phase I/Ii Iconic Trial Of The Icos Agonist Vopratelimab Alone And With Nivolumab: Icos-High Cd4 T-Cell Populations And Predictors Of Response, Timothy A Yap, Russell K Pachynski, Haeseong Park, Et Al

2020-Current year OA Pubs

PURPOSE: The first-in-human phase I/II ICONIC trial evaluated an investigational inducible costimulator (ICOS) agonist, vopratelimab, alone and in combination with nivolumab in patients with advanced solid tumors.

PATIENTS AND METHODS: In phase I, patients were treated with escalating doses of intravenous vopratelimab alone or with nivolumab. Primary objectives were safety, tolerability, MTD, and recommended phase II dose (RP2D). Phase II enriched for ICOS-positive (ICOS+) tumors; patients were treated with vopratelimab at the monotherapy RP2D alone or with nivolumab. Pharmacokinetics, pharmacodynamics, and predictive biomarkers of response to vopratelimab were assessed.

RESULTS: ICONIC enrolled 201 patients. Vopratelimab alone and with nivolumab was …

Living With Cervical Spinal Cord Injury During The Covid-19 Pandemic: A Qualitative Study, Elspeth J R Hill, Allison J L'Hotta, Carie R Kennedy, Aimee S James, Ida K Fox

2020-Current year OA Pubs

OBJECTIVE: To understand how COVID-19 has affected the daily lives of people living with cervical spinal cord injury (SCI).

DESIGN: Cross sectional qualitative study.

SETTING: Academic medical center in the Midwestern United States.

PARTICIPANTS: Ten community-dwelling individuals (8 men, 2 women), average 11.6 years post-mid-cervical level SCI (N=10).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Semistructured interviews were completed by phone. The research team used thematic analysis and inductive strategies to analyze the data in this exploratory investigation.

RESULTS: People with cervical SCI living in the United States during the spring of 2020 experienced changes to their daily lives. Participants described …

Substance Use And Common Contributors To Morbidity: A Genetics Perspective, Sandra Sanchez-Roige, Rachel L Kember, Arpana Agrawal

2020-Current year OA Pubs

Excessive substance use and substance use disorders (SUDs) are common, serious and relapsing medical conditions. They frequently co-occur with other diseases that are leading contributors to disability worldwide. While heavy substance use may potentiate the course of some of these illnesses, there is accumulating evidence suggesting common genetic architectures. In this narrative review, we focus on four heritable medical conditions - cardiometabolic disease, chronic pain, depression and COVID-19, which are commonly overlapping with, but not necessarily a direct consequence of, SUDs. We find persuasive evidence of underlying genetic liability that predisposes to both SUDs and chronic pain, depression, and COVID-19. …

A Mid-Level Health Manager Intervention To Promote Uptake Of Isoniazid Preventive Therapy Among People With Hiv In Uganda: A Cluster Randomised Trial, Elijah Kakande, Elvin H Geng, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice.

METHODS: We conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control …

An Ips-Derived In Vitro Model Of Human Atrial Conduction, Sherri M Biendarra-Tiegs, Sergey Yechikov, Bhupinder Shergill, Brittany Brumback, Kentaro Takahashi, Venktesh S Shirure, Ruth Estelle Gonzalez, Laura Houshmand, Denise Zhong, Kuo-Chan Weng, Jon Silva, Timothy W Smith, Stacey L Rentschler, Steven C George

2020-Current year OA Pubs

Atrial fibrillation (AF) is the most common arrhythmia in the United States, affecting approximately 1 in 10 adults, and its prevalence is expected to rise as the population ages. Treatment options for AF are limited; moreover, the development of new treatments is hindered by limited (1) knowledge regarding human atrial electrophysiological endpoints (e.g., conduction velocity [CV]) and (2) accurate experimental models. Here, we measured the CV and refractory period, and subsequently calculated the conduction wavelength, in vivo (four subjects with AF and four controls), and ex vivo (atrial slices from human hearts). Then, we created an in vitro model of …

Wolf's Isotopic Response Of Lichen Planus Following Contact Dermatitis, Bruin Pollard, William H Mccoy Iv, Craig L Leonardi, Ann G Martin

2020-Current year OA Pubs

No abstract provided.

Efficacy And Safety Of Ofatumumab In Recently Diagnosed, Treatment-Naive Patients With Multiple Sclerosis: Results From Asclepios I And Ii, Jutta Gärtner, Stephen L Hauser, Amit Bar-Or, Xavier Montalban, Jeffrey A Cohen, Anne H Cross, Kumaran Deiva, Habib Ganjgahi, Dieter A Häring, Bingbing Li, Ratnakar Pingili, Krishnan Ramanathan, Wendy Su, Roman Willi, Bernd Kieseier, Ludwig Kappos

2020-Current year OA Pubs

BACKGROUND: In the phase III ASCLEPIOS I and II trials, participants with relapsing multiple sclerosis receiving ofatumumab had significantly better clinical and magnetic resonance imaging (MRI) outcomes than those receiving teriflunomide.

OBJECTIVES: To assess the efficacy and safety of ofatumumab versus teriflunomide in recently diagnosed, treatment-naive (RDTN) participants from ASCLEPIOS.

METHODS: Participants were randomized to receive ofatumumab (20 mg subcutaneously every 4 weeks) or teriflunomide (14 mg orally once daily) for up to 30 months. Endpoints analysed post hoc in the protocol-defined RDTN population included annualized relapse rate (ARR), confirmed disability worsening (CDW), progression independent of relapse activity (PIRA) and …

Risk Factors And Medical Resource Utilization In Us Adults Hospitalized With Influenza Or Respiratory Syncytial Virus In The Hospitalized Acute Respiratory Tract Infection Study, Jessica Hartnett, Prina Donga, Gabriela Ispas, Yannick Vandendijck, David Anderson, Stacey House, Selim Suner

2020-Current year OA Pubs

BACKGROUND: Influenza and respiratory syncytial virus (RSV) are associated with substantial morbidity and mortality in the United States. We assessed risk factors for severe disease and medical resource utilization (MRU) among US adults hospitalized with influenza or RSV in the Hospitalized Acute Respiratory Tract Infection (HARTI) study.

METHODS: HARTI was a prospective global (40 centers, 12 countries) epidemiological study of adults hospitalized with acute respiratory tract infections conducted across the 2017-2019 epidemic seasons. Patients with confirmed influenza or RSV were followed up to 3 months post-discharge. Baseline characteristics, prevalence of core risk factors (CRFs) for severe disease (age ≥65 years, …

Association Of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest, Ericka L Fink, Stuart Friess, Et Al.

2020-Current year OA Pubs

Importance: Families and clinicians have limited validated tools available to assist in estimating long-term outcomes early after pediatric cardiac arrest. Blood-based brain-specific biomarkers may be helpful tools to aid in outcome assessment.

Objective: To analyze the association of blood-based brain injury biomarker concentrations with outcomes 1 year after pediatric cardiac arrest.

Design, Setting, and Participants: The Personalizing Outcomes After Child Cardiac Arrest multicenter prospective cohort study was conducted in pediatric intensive care units at 14 academic referral centers in the US between May 16, 2017, and August 19, 2020, with the primary investigators blinded to 1-year outcomes. The study included …

Measuring Transcription Factor Binding And Gene Expression Using Barcoded Self-Reporting Transposon Calling Cards And Transcriptomes, Matthew Lalli, Allen Yen, Urvashi Thopte, Fengping Dong, Arnav Moudgil, Xuhua Chen, Jeffrey Milbrandt, Joseph D Dougherty, Robi D Mitra

2020-Current year OA Pubs

Calling cards technology using self-reporting transposons enables the identification of DNA-protein interactions through RNA sequencing. Although immensely powerful, current implementations of calling cards in bulk experiments on populations of cells are technically cumbersome and require many replicates to identify independent insertions into the same genomic locus. Here, we have drastically reduced the cost and labor requirements of calling card experiments in bulk populations of cells by introducing a DNA barcode into the calling card itself. An additional barcode incorporated during reverse transcription enables simultaneous transcriptome measurement in a facile and affordable protocol. We demonstrate that barcoded self-reporting transposons recover

Perspectives Of Participation In Daily Life From Cancer Survivors: A Qualitative Analysis, Allison J L'Hotta, Nirmala Shivakumar, Kathleen D Lyons, Audrey Trebelhorn, Annamayil Manohar, Allison A King

2020-Current year OA Pubs

OBJECTIVE: To characterize how survivors of cancer define participation.

DESIGN: Cross-sectional qualitative study.

SETTING: Participants were enrolled from a large academic medical center in the Midwestern United States. Interviews were conducted over Zoom or phone.

PARTICIPANTS: Survivors of cancer (N=40) with brain, breast, colorectal, or lung cancer (n=10 per group). Participants were purposively sampled to maximize variation in the study sample. Participant ages ranged from 26-83 years, with a mean age of 55 years. Seventy percent of participants were receiving active cancer treatment at the time of the interview.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Participant perspectives gathered from 1-on-1 …

Reference Ranges For Corpus Callosum And Cavum Septi Pellucidi Biometry On Prenatal Ultrasound: Systematic Review And Meta-Analysis, Joshua I Rosenbloom, Lauren H Yaeger, Shay Porat

2020-Current year OA Pubs

We conducted a systematic review and meta-analysis of published nomograms for fetal corpus callosum and cavum septi pellucid biometry. A structured literature search was conducted to identify studies that reported normal measurements of the fetal corpus callosum and cavum septi pellucidi. Random effects metaanalysis was used to calculate normal ranges, and reference curves are provided. The quality assessment demonstrated that there was generally poor reporting regarding maternal characteristics and neonatal outcomes. Our findings emphasize that standardization of research protocols and publishing criteria for normal biometric ranges is needed.

Evolution Of Multiple Domains Of The Hiv-1 Envelope Glycoprotein During Coreceptor Switch With Ccr5 Antagonist Therapy, Yueqi Du, Ellen Wu, Xiang Gao, Jie Zhang, John C Martin, Bruce A Rosa, Makedonka Mitreva, Lee Ratner

2020-Current year OA Pubs

HIV-1 uses CD4 as a receptor and chemokine receptors CCR5 and/or CXCR4 as coreceptors. CCR5 antagonists are a class of antiretrovirals used to inhibit viral entry. Phenotypic prediction algorithms such as Geno2Pheno are used to assess CCR5 antagonist eligibility, for which the V3 region is screened. However, there exist scenarios where the algorithm cannot give an accurate prediction of tropism. The current study examined coreceptor shift of HIV-1 from CCR5-tropic strains to CXCR4-tropic or dual-tropic strains among five subjects in a clinical trial of the CCR5 antagonist vicriviroc. Envelope gene amplicon libraries were constructed and subjected to next-generation sequencing, as …

Optimal Urine Culture Diagnostic Stewardship Practice- Results From An Expert Modified-Delphi Procedure, Kimberly C Claeys, Stephen Y Liang, Et Al.

2020-Current year OA Pubs

BACKGROUND: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship.

METHODS: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen …

Proteomic Identification Of Potential Target Proteins Of Cathepsin W For Its Development As A Drug Target For Influenza, Sira C Günther, Carles Martínez-Romero, Milagros Sempere Borau, Christine T N Pham, Adolfo García-Sastre, Silke Stertz

2020-Current year OA Pubs

Influenza A virus (IAV) coopts numerous host factors for efficient replication. The cysteine protease cathepsin W (CTSW) has been identified as one host factor required for IAV entry, specifically for the escape of IAVs from late endosomes. However, the substrate specificity of CTSW and the proviral mechanism are thus far unknown. Here, we show that intracellular but not secreted CTSW promotes viral entry. We reveal 79 potential direct and 31 potential indirect cellular target proteins of CTSW using the high-throughput proteomic approach terminal amine isotopic labeling of substrates (TAILS) and determine the cleavage motif shared by the substrates of CTSW. …

Membrane Integrity Contributes To Resistance Of Cryptococcus Neoformans To The Cell Wall Inhibitor Caspofungin, Brenda Moreira-Walsh, Abigail Ragsdale, Woei Lam, Rajendra Upadhya, Evan Xu, Jennifer K Lodge, Maureen J Donlin

2020-Current year OA Pubs

The fungal pathogen Cryptococcus neoformans causes up to 278 000 infections each year globally, resulting in up to 180,000 deaths annually, mostly impacting immunocompromised people. Therapeutic options for C. neoformans infections are very limited. Caspofungin, a member of the echinocandin class of antifungals, is generally well tolerated but clinically ineffective against C. neoformans. We sought to identify biological processes that can be targeted to render the cell more susceptible to echinocandins by screening the available libraries of gene deletion mutants made in the KN99α background for caspofungin sensitivity. We adapted a Candida albicans fungal biofilm assay for the growth characteristics …

Re-Examining Rotavirus Innate Immune Evasion: Potential Applications Of The Reverse Genetics System, Avan Antia, Amanda N Pinski, Siyuan Ding

2020-Current year OA Pubs

Rotaviruses represent one of the most successful pathogens in the world, with high infectivity and efficient transmission between the young of many animal species, including humans. To overcome host defenses, rotaviruses have evolved a plethora of strategies to effectively evade the innate immune response, establish initial infection in the small intestine, produce progeny, and shed into the environment. Previously, studying the roles and relative contributions of specific rotaviral factors in innate immune evasion had been challenging without a plasmid-only reverse genetics system. Although still in its infancy, current reverse genetics technology will help address important research questions regarding rotavirus innate …

Blocking Chop-Dependent Txnip Shuttling To Mitochondria Attenuates Albuminuria And Mitigates Kidney Injury In Nephrotic Syndrome, Sun-Ji Park, Yeawon Kim, Chuang Li, Junwoo Suh, Jothilingam Sivapackiam, Tassia M Goncalves, George Jarad, Guoyan Zhao, Fumihiko Urano, Vijay Sharma, Ying Maggie Chen

2020-Current year OA Pubs

Albuminuria is a hallmark of glomerular disease of various etiologies. It is not only a symptom of glomerular disease but also a cause leading to glomerulosclerosis, interstitial fibrosis, and eventually, a decline in kidney function. The molecular mechanism underlying albuminuria-induced kidney injury remains poorly defined. In our genetic model of nephrotic syndrome (NS), we have identified CHOP (C/EBP homologous protein)-TXNIP (thioredoxin-interacting protein) as critical molecular linkers between albuminuria-induced ER dysfunction and mitochondria dyshomeostasis. TXNIP is a ubiquitously expressed redox protein that binds to and inhibits antioxidant enzyme, cytosolic thioredoxin 1 (Trx1), and mitochondrial Trx2. However, very little is known about …

A Pilot Randomized Trial To Examine Effects Of A Hybrid Closed-Loop Insulin Delivery System On Neurodevelopmental And Cognitive Outcomes In Adolescents With Type 1 Diabetes, Allan L Reiss, Ana Maria Arbelaez, Et Al

2020-Current year OA Pubs

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system. Eligibility criteria for participation in the study included age between 14 and 17 years and a diagnosis of T1D before 8 years of age. Randomization to either a hybrid closed-loop or standard diabetes care group was performed …

Distinct Sensitivities To Sars-Cov-2 Variants In Vaccinated Humans And Mice, Alexandra C Walls, Laura A Vanblargan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to the development of a large number of vaccines, several of which are now approved for use in humans. Understanding vaccine-elicited antibody responses against emerging SARS-CoV-2 variants of concern (VOCs) in real time is key to inform public health policies. Serum neutralizing antibody titers are the current best correlate of protection from SARS-CoV-2 challenge in non-human primates and a key metric to understand immune evasion of VOCs. We report that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses elicited …

Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S. Regalado, Alan C. Braverman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.

OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.

METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, …

N1-Methylpseudouridine Found Within Covid-19 Mrna Vaccines Produces Faithful Protein Products, Kyusik Q Kim, Bhagyashri D Burgute, Shin-Cheng Tzeng, Crystal Jing, Courtney Jungers, Junya Zhang, Liewei L Yan, Richard D Vierstra, Sergej Djuranovic, Bradley S Evans, Hani S Zaher

2020-Current year OA Pubs

Synthetic mRNA technology is a promising avenue for treating and preventing disease. Key to the technology is the incorporation of modified nucleotides such as N1-methylpseudouridine (m1Ψ) to decrease immunogenicity of the RNA. However, relatively few studies have addressed the effects of modified nucleotides on the decoding process. Here, we investigate the effect of m1Ψ and the related modification pseudouridine (Ψ) on translation. In a reconstituted system, we find that m1Ψ does not significantly alter decoding accuracy. More importantly, we do not detect an increase in miscoded peptides when mRNA containing m1Ψ is translated in cell culture, compared with unmodified mRNA. …

A Multitrait Locus Regulates Sarbecovirus Pathogenesis, Alexandra Schäfer, Emma S Winkler, Michael S Diamond, Et Al

2020-Current year OA Pubs

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential …

Spatiotemporal Correlation Analysis Of Hydraulic Fracturing And Stroke In The United States, Chuanbo Hu, Bin Liu, Shuo Wang, Zhenduo Zhu, Amelia Adcock, James Simpkins, Xin Li

2020-Current year OA Pubs

Hydraulic fracturing or fracking has led to a rapid growth of oil and gas production in the United States, but the impact of fracking on public health is an important but underresearched topic. We designed a methodology to study spatiotemporal correlations between the risk of fracking and stroke mortality. An annualized loss expectancy (ALE) model is applied to quantify the risk of fracking. The geographically and temporally weighted regression (GTWR) model is used to analyze spatiotemporal correlations of stroke mortality, fracking ALE, and nine other socioeconomic- and health-related factors. The analysis shows that fracking ALE is moderately correlated with stroke …

Subcortical-Cortical Dynamical States Of The Human Brain And Their Breakdown In Stroke, Chiara Favaretto, Michele Allegra, Gustavo Deco, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Andrea Brovelli, Maurizio Corbetta

2020-Current year OA Pubs

The mechanisms controlling dynamical patterns in spontaneous brain activity are poorly understood. Here, we provide evidence that cortical dynamics in the ultra-slow frequency range (<0.01-0.1 Hz) requires intact cortical-subcortical communication. Using functional magnetic resonance imaging (fMRI) at rest, we identify Dynamic Functional States (DFSs), transient but recurrent clusters of cortical and subcortical regions synchronizing at ultra-slow frequencies. We observe that shifts in cortical clusters are temporally coincident with shifts in subcortical clusters, with cortical regions flexibly synchronizing with either limbic regions (hippocampus/amygdala), or subcortical nuclei (thalamus/basal ganglia). Focal lesions induced by stroke, especially those damaging white matter connections between basal ganglia/thalamus and cortex, provoke anomalies in the fraction times, dwell times, and transitions between DFSs, causing a bias toward abnormal network integration. Dynamical anomalies observed 2 weeks after stroke recover in time and contribute to explaining neurological impairment and long-term outcome.