71 results on '"Natalie Ko"'
Search Results
2. The viability and acceptability of a Virtual Wound Care Command Centre in Australia
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Michelle Barakat‐Johnson, Badia Kita, Aaron Jones, Mitchell Burger, David Airey, John Stephenson, Thomas Leong, Jana Pinkova, Georgina Frank, Natalie Ko, Andrea Kirk, Astrid Frotjold, Kate White, and Fiona Coyer
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Wound Healing ,Trauma Centers ,Australia ,Humans ,Surgery ,Dermatology ,Referral and Consultation - Abstract
The objective of this study was to assess the viability and acceptability of an innovative Virtual Wound Care Command Centre where patients in the community, and their treating clinicians, have access to an expert wound specialist service that comprises a digitally enabled application for wound analysis, decision-making, remote consultation, and monitoring. Fifty-one patients with chronic wounds from 9 centres, encompassing hospital services, outpatient clinics, and community nurses in one metropolitan and rural state in Australia, were enrolled and a total of 61 wounds were analysed over 7 months. Patients received, on average, an occasion of service every 4.4 days, with direct queries responded to in a median time of 1.5 hours. During the study period, 26 (42.6%) wounds were healed, with a median time to healing of 66 (95% CI: 56-88) days. All patients reported high satisfaction with their wound care, 86.4% of patients recommended the Virtual Wound Care Command Centre with 84.1% of patients reporting the digital wound application as easy to use. Potential mean travel savings of $99.65 for rural patients per visit were recognised. The data revealed that the Virtual Wound Care Command Centre was a viable and acceptable patient-centred expert wound consultation service for chronic wound patients in the community.
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- 2022
3. Clinician Knowledge of Incontinence-Associated Dermatitis
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Michelle Barakat-Johnson, John Stephenson, Shifa Basjarahil, Jayne Campbell, Michelle Cunich, Gary Disher, Samara Geering, Natalie Ko, Michelle Lai, Catherine Leahy, Thomas Leong, Eve McClure, Melissa O'Grady, Joan Walsh, Kate White, and Fiona Coyer
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Advanced and Specialized Nursing ,Medical–Surgical Nursing ,Cross-Sectional Studies ,Surveys and Questionnaires ,Humans ,Dermatitis ,Skin Care ,Delivery of Health Care ,Fecal Incontinence - Abstract
This study examined clinicians' knowledge of incontinence-associated dermatitis (IAD) using the Barakat-Johnson Incontinence-Associated Dermatitis Knowledge Tool (Know-IAD).A cross-sectional multicenter survey.The setting was 6 hospitals across 5 health districts in New South Wales, Australia. The participants were nurses (registered nurses and enrolled nurses), physicians, allied health (occupational therapists, dietitians, and physiotherapists), and students (nursing and allied health).Data about IAD knowledge were collected from November 2019 to January 2020. The Know-IAD, an 18-item validated instrument that measures knowledge of IAD in 3 domains (etiology and risk, classification and diagnosis, and prevention and management), was administered to a cross section of eligible clinicians. The participants anonymously completed hard copy surveys. Descriptive and exploratory analyses were conducted to quantify clinicians' knowledge about the etiology and risk, classification and diagnosis, and prevention and management of IAD. A mean knowledge score of 70% was considered to be satisfactory.Four hundred twelve respondents completed the survey. One hundred twenty nine respondents (31.3%) achieved 70% correct responses and greater for the entire set of items. For the etiology and risk domain, 348 respondents (84.5%) obtained a score of 70% correct responses and greater, 67 respondents (16.3%) achieved 70% correct responses and greater for the classification and diagnosis domain, and 84 respondents (20.4%) achieved 70% correct responses and greater for the prevention and management domain.Clinicians tend to have low knowledge and recognition of IAD, particularly in the areas of classification and diagnosis along with prevention and management. They tend to have higher knowledge of how IAD is caused and the risk factors. This study has identified knowledge gaps for further education that can improve assessment, prevention, and management of IAD.
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- 2022
4. Corrigendum to 'The costs, health outcomes and cost-effectiveness of interventions for the prevention and treatment of incontinence-associated dermatitis: A systematic review' [Int. J. Nurs. Stud. 129 (2022) 104216]
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Michelle Cunich, Michelle Barakat-Johnson, Michelle Lai, Sheena Arora, Jody Church, Shifa Basjarahil, Jayne L. Campbell, Gary Disher, Samara Geering, Natalie Ko, Catherine Leahy, Thomas Leong, Eve McClure, Melissa O'Grady, Joan Walsh, Kate White, and Fiona Coyer
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General Nursing - Published
- 2023
5. The costs, health outcomes and cost-effectiveness of interventions for the prevention and treatment of incontinence-associated dermatitis: A systematic review
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Michelle Cunich, Michelle Barakat-Johnson, Michelle Lai, Sheena Arora, Jody Church, Shifa Basjarahil, Jayne L. Campbell, Gary Disher, Samara Geering, Natalie Ko, Catherine Leahy, Thomas Leong, Eve McClure, Melissa O'Grady, Joan Walsh, Kate White, and Fiona Coyer
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Male ,Urinary Incontinence ,Cost-Benefit Analysis ,Outcome Assessment, Health Care ,Quality of Life ,Humans ,Dermatitis ,Female ,1110 Nursing ,Nursing ,health care economics and organizations ,General Nursing - Abstract
BACKGROUND: Incontinence-associated dermatitis is a common, under-recognized painful skin condition associated with poorer quality of life, increased nurse workloads, and costs. OBJECTIVE: To systematically review economic evidence for the prevention and treatment of incontinence-associated dermatitis. DESIGN: Systematic review of quantitative research. DATA SOURCES: PubMed, MEDLINE, EMBASE, Cochrane Library, York Centre for Reviews and Dissemination database, Econlit, Tufts' Cost-Effectiveness Analysis Registry, and Web of Science. REVIEW METHODS: A comprehensive search for studies on resource use (costs), health outcomes, and cost-effectiveness of interventions for incontinence-associated dermatitis was conducted. Screening, data extraction, and initial quality assessment were conducted independently by two reviewers, with disagreements/queries regarding quality settled through consensus with the larger team. Quality evaluated using the Consolidated Health Economic Evaluation Reporting Standards checklist and results narratively arranged. FINDINGS: Seventeen studies (10 for prevention, one for treatment and six for both prevention and treatment) included. All studies measured resource use from a healthcare provider perspective; 14 quantified resources in monetary terms. Considerable variation existed in the resource use data primarily due to differences in the type of resources counted, selected time horizons, valuation methods, and reporting approaches. Ten studies provided evidence of their intervention to be cost saving (or at least cost avoiding). Five studies on barrier products provided evidence to be cost saving: three for prevention, one for treatment, and one for both prevention and treatment. Two studies of cleanser and barrier products provided evidence to be cost saving for the prevention and treatment of incontinence-associated dermatitis. One study found a cleanser to be a cost saving preventative intervention. One bowel management system was found to be cost saving over time only, and one nurse education intervention was found to be cost saving for preventing and treating incontinence-associated dermatitis. One barrier product was found to be cost-effective for preventing and treating the condition. Finally, one study found a cleanser and barrier product was time saving for prevention. None of the studies incorporated a multi-attribute quality of life measure; however, two studies included person-reported outcome measures for pain. A narrow range of resources (mainly products) were considered, and there was limited information on how they were counted and valued. Analyses relating to heterogeneity among patients/hospital wards or health facilities and uncertainty were lacking. CONCLUSIONS: Barrier products are possibly a more cost-effective treatment than others; however, this evidence lacks certainty. Structured health economic evaluations are required for a reliable evidence-base on the interventions for incontinence-associated dermatitis. TWEETABLE ABSTRACT: Most incontinence-associated dermatitis studies lack person-reported outcomes, costs beyond product/staff time, and economic evaluation.
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- 2022
6. Vaccine hesitancy in patients presenting to a specialized allergy center: clinical relevant sensitizations, impact on mental health and vaccination rates
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Natalie Kogseder, Viktoria Puxkandl, Wolfram Hoetzenecker, and Sabine Altrichter
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allergy ,COVID ,vaccine ,prick-test ,Hospital Anxiety and Depression Scale (HADS) ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionThe COVID vaccination program with new types of vaccinations and early reports of allergic reactions to vaccines led to vaccination hesitancy in patients with allergies. In this study, we aimed to characterize patients who present at an allergy center with specific questions regarding risk assessment to COVID vaccines in comparison to regular allergy center patients.MethodsA total of 50 patient charts of patients with risk assessment for COVID vaccination (COV group) and 50 regular allergy center patients (ALL group) were assessed for documented allergies, comorbidities, total IgE, and tryptase levels and hospital anxiety and depression score (HADS). Skin prick testing (SPT) with additives of COVID vaccines [polyethylene glycol (PEG), polysorbate] were performed if indicated based on medical history.ResultsPatients who presented for examination prior to a possible COVID vaccination were mostly female (86%) and had more frequently reported allergic reactions to drugs in the past, but only in a minor group (28%) were the reactions qualified as anaphylaxis. The group COV patients scored significantly higher in the HADS for anxiety and depression than the regular group ALL patients. The same trend was observed when data were corrected for gender. It is worth noting that patients without any prior contact to COVID vaccines scored comparable regarding anxiety to patients with prior reaction to COVID vaccinations, but significantly higher in the depression score. In 19 patients (38%) who met the indications for SPT for the suspicious contents PEG and Polysorbate 80, the tests did not show a positive result. Furthermore, 84% of patients underwent the prick test, but only 15% of patients who received consultation alone agreed to vaccination at our center. No vaccination-related event was documented in these patients.DiscussionIn conclusion, vaccination hesitancy was frequently elicited by negative experiences with drugs and putative drug allergies. Female patients predominate in this patient group, and the anxiety and depression scores were significantly elevated. Allergological workup, including SPT, led to a high rate of subsequent vaccinations, whereas a discussion with the patients about risks and individualized advice for vaccination without testing only rarely resulted in documented vaccinations.
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- 2024
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7. Implementing best available evidence into practice for incontinence-associated dermatitis in Australia: A multisite multimethod study protocol
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Michelle Barakat-Johnson, Fiona Coyer, Catherine Leahy, Shifa Basjarahil, Samara Geering, Gary Disher, Joan Walsh, Michelle Lai, Natalie Ko, Jayne Campbell, Katherine M. White, Eve McClure, Melissa O'Grady, Michelle Cunich, and Thomas Leong
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Adult ,Male ,Adolescent ,Translational research ,Dermatology ,Audit ,Dermatitis, Contact ,Pathology and Forensic Medicine ,Translational Research, Biomedical ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Nursing ,Clinical Protocols ,Surveys and Questionnaires ,Prevalence ,Medicine ,Humans ,Qualitative Research ,Protocol (science) ,Data collection ,030504 nursing ,Pressure injury ,business.industry ,Australia ,Guideline ,Focus Groups ,Middle Aged ,Focus group ,Urinary Incontinence ,Quality of Life ,Female ,0305 other medical science ,business ,Fecal Incontinence - Abstract
Aims Incontinence-associated dermatitis (IAD) is an insidious and under-reported hospital-acquired complication which substantially impacts on patients’ quality of life. A published international guideline and the Ghent Global IAD Categorisation Tool (GLOBIAD) outline the best available evidence for the optimal management of IAD. This study aims to implement theguideline and the GLOBIAD tool and evaluate the effect on IAD occurrences and sacral pressure injuries as well as patient, clinician and cost-effectiveness outcomes. Materials and methods The study will employ a multi-method design across six hospitals in five health districts in Australia, and will be conducted in three phases (pre-implementation, implementation and post-implementation) over 19 months. Data collection will involve IAD and pressure injury prevalence audits for patient hospital admissions, focus groups with, and surveys of, clinicians, patient interviews, and collection of the cost of IAD hospital care and patient-related outcomes including quality of life. Eligible participants will be hospitalised adults over 18 years of age experiencing incontinence, and clinicians working in the study wards will be invited to participate in focus groups and surveys. Conclusion The implementation of health district-wide evidence-based practices for IAD using a translational research approach that engages key stakeholders will allow the standardisation of IAD care that can potentially be applicable to a range of settings. Knowledge gained will inform future practice change in patient care and health service delivery and improve the quality of care for patients with IAD. Support at the hospital, state and national levels, coupled with a refined stakeholder-inclusive strategy, will enhance this project's success, sustainability and scalability beyond this existing project.
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- 2020
8. The Effects of Hot Isostatic Pressing (HIP) and Heat Treatment on the Microstructure and Mechanical Behavior of Electron Beam-Melted (EBM) Ti–6Al–4V Alloy and Its Susceptibility to Hydrogen
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Noa Lulu-Bitton, Nissim U. Navi, Shlomo Haroush, Eyal Sabatani, Natalie Kostirya, Eitan Tiferet, Yaron I. Ganor, Ofer Omesi, Gennadi Agronov, and Noam Eliaz
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additive manufacturing (AM) ,electron beam melting (EBM) ,Ti–6Al–4V alloy ,titanium hydride ,hydrogen embrittlement (HE) ,small punch test (SPT) ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
The effects of the secondary processes of Hot Isostatic Pressing (HIP) at 920 °C and Heat Treatment (HT) at 1000 °C of Electron Beam-Melted (EBM) Ti–6Al–4V alloy on the microstructure and hydrogen embrittlement (HE) after electrochemical hydrogen charging (EC) were investigated. Comprehensive characterization, including microstructural analysis, X-ray diffraction (XRD), thermal desorption analysis, and mechanical testing, was conducted. After HIP, the β-phase morphology changed from discontinuous Widmanstätten to a more continuous structure, 10 times and ~1.5 times larger in length and width, respectively. Following HT, the β-phase morphology changed to a continuous “web-like” structure, ~4.5 times larger in width. Despite similar mechanical behavior in their non-hydrogenated state, the post-treated alloys exhibit increased susceptibility to HE due to enhanced hydrogen penetration into the bulk. It is shown that hydrogen content in the samples’ bulk is inversely dependent on surface hydride content. It is therefore concluded that the formed hydride surface layer is crucial for inhibiting further hydrogen penetration and adsorption into the bulk and thus for reducing HE susceptibility. The lack of a hydride surface layer in the samples subject to HIP and HT highlights the importance of choosing secondary treatment process parameters that will not increase the continuous β-phase morphology of EBM Ti–6Al–4V alloys in applications that involve electrochemical hydrogen environments.
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- 2024
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9. CRISPR‐based environmental DNA detection for a rare endangered estuarine species
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Raman P. Nagarajan, Leigh Sanders, Natalie Kolm, Alejandro Perez, Taylor Senegal, Brian Mahardja, Melinda R. Baerwald, and Andrea D. Schreier
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Clustered regularly interspaced short palindromic repeats ,environmental DNA ,endangered species ,estuaries ,Osmeriformes ,Environmental sciences ,GE1-350 ,Microbial ecology ,QR100-130 - Abstract
AbstractEnvironmental DNA (eDNA) methods complement traditional aquatic monitoring surveys and are especially advantageous for rare and listed species to detect spatial and temporal distribution patterns. However, improvements in ease of use and portability could increase the utility of eDNA methods, leading to more widespread application, including expanding its role in management decision‐making processes. We describe the development of an eDNA detection assay for delta smelt (Hypomesus transpacificus), an endangered fish in the San Francisco Estuary, using SHERLOCK (Specific High‐Sensitivity Enzymatic Reporter Unlocking). SHERLOCK is a clustered regularly interspaced short palindromic repeats (CRISPR)‐based diagnostic tool with the ability to detect species‐specific genetic variants, making it ideal for genetic‐based taxonomic identification of any organism. Because of its high sensitivity and specificity, SHERLOCK is adaptable to eDNA detection in water samples. Here, we describe adaptation of a delta smelt SHERLOCK assay for use with estuarine water eDNA samples. This version of the assay exhibits increased sensitivity compared to the original delta smelt SHERLOCK protocol (new limit of detection approximately three copies per reaction compared to ~300 in original assay) and successfully detected delta smelt eDNA in both experimental and natural contexts. Overall, our results demonstrate that SHERLOCK eDNA detection offers managers an alternative, isothermal methodology, and highlights some challenges for detection of rare, endangered species at low abundance.
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- 2024
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10. Gender, Race, and Ethnicity in Critical Care Fellowship Programs in the United States From 2016 to 2021
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Stephen M. Pastores, MD, Natalie Kostelecky, RN, and Hao Zhang, MD
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Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
IMPORTANCE:. A diverse and inclusive critical care workforce is vital to the provision of culturally appropriate and effective care to critically ill patients of all backgrounds. OBJECTIVES:. The purpose of this study is to determine the trends in gender, race, and ethnicity of U.S. critical care fellowships over the past 6 years (2016–2021). METHODS:. Data on gender, race, and ethnicity of critical care fellows in five Accreditation Council on Graduate Medical Education-accredited training programs (internal medicine, pulmonary and critical care, anesthesiology, surgery, and pediatrics) from 2015 to 2016 to 2020–2021 were obtained from the joint reports of the American Medical Association (AMA) and Association of American Medical Colleges published annually in the Journal of the AMA. RESULTS:. From 2016 to 2021, the number of U.S. critical care fellows increased annually, up 23.8%, with the largest number of fellows in pulmonary critical care medicine (60.1%). The percentage of female critical care fellows slightly increased from 38.7% to 39.4% (p = 0.57). White fellows significantly decreased from 57.4% to 49.3% (p = 0.0001); similarly, Asian fellows significantly decreased from 30.8% to 27.5% (p = 0.004). The percentage of Black or African American fellows was not statistically significantly different (4.9% vs 4.4%; p = 0.44). The number of fellows who self-identified as multiracial significantly increased from 52 (1.9%) to 91 (2.7%) (p = 0.043). The percentage of fellows who identified as Hispanic was not significantly different (6.7% vs 7.5%; p = 0.23). CONCLUSIONS:. The percentage of women and racially and ethnically minoritized fellows (Black and Hispanic) remain underrepresented in critical care fellowship programs. Additional research is needed to better understand these demographic trends in our emerging critical care physician workforce and enhance diversity.
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- 2023
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11. HDF1, a novel flowering time regulator identified in a mutant suppressing sensitivity to red light reduced 1 early flowering
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Mikael Johansson, Alexander Steffen, Martin Lewinski, Natalie Kobi, and Dorothee Staiger
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Medicine ,Science - Abstract
Abstract Arabidopsis SENSITIVITY TO RED LIGHT REDUCED 1 (SRR1) delays the transition from vegetative to reproductive development in noninductive conditions. A second-site suppressor screen for novel genes that overcome early flowering of srr1-1 identified a range of suppressor of srr1-1 mutants flowering later than srr1-1 in short photoperiods. Here, we focus on mutants flowering with leaf numbers intermediate between srr1-1 and Col. Ssm67 overcomes srr1-1 early flowering independently of day-length and ambient temperature. Full-genome sequencing and linkage mapping identified a causative SNP in a gene encoding a Haloacid dehalogenase superfamily protein, named HAD-FAMILY REGULATOR OF DEVELOPMENT AND FLOWERING 1 (HDF1). Both, ssm67 and hdf1-1 show increased levels of FLC, indicating that HDF1 is a novel regulator of this floral repressor. HDF1 regulates flowering largely independent of SRR1, as the effect is visible in srr1-1 and in Col, but full activity on FLC may require SRR1. Furthermore, srr1-1 has a delayed leaf initiation rate that is dependent on HDF1, suggesting that SRR1 and HDF1 act together in leaf initiation. Another mutant flowering intermediate between srr1-1 and wt, ssm15, was identified as a new allele of ARABIDOPSIS SUMO PROTEASE 1, previously implicated in the regulation of FLC stability.
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- 2023
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12. The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma
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Jens Bauer, Natalie Köhler, Yacine Maringer, Philip Bucher, Tatjana Bilich, Melissa Zwick, Severin Dicks, Annika Nelde, Marissa Dubbelaar, Jonas Scheid, Marcel Wacker, Jonas S. Heitmann, Sarah Schroeder, Jonas Rieth, Monika Denk, Marion Richter, Reinhild Klein, Irina Bonzheim, Julia Luibrand, Ursula Holzer, Martin Ebinger, Ines B. Brecht, Michael Bitzer, Melanie Boerries, Judith Feucht, Helmut R. Salih, Hans-Georg Rammensee, Stephan Hailfinger, and Juliane S. Walz
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Science - Abstract
The DNAJB1-PRKACA fusion transcript is the oncogenic driver in fibrolamellar hepatocellular carcinoma, a lethal disease with limited therapeutic options. Here, the authors identify the DNAJB1-PRKACA protein as a source for immunogenic neoepitopes and a potential target of T cell-based immunotherapy.
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- 2022
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13. First clinical experience with real-time portal imaging-based breath-hold monitoring in tangential breast radiotherapy
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Elena N. Vasina, Natalie Kong, Peter Greer, Jose Baeza Ortega, Tomas Kron, Joanna J. Ludbrook, David Thwaites, and Joerg Lehmann
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Real-time monitoring ,Electronic portal imaging device ,EPID ,Tangential breast radiotherapy ,Internal anatomy ,Deep inspiration breath-hold ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background and purpose: Real-time treatment monitoring with the electronic portal imaging device (EPID) can conceptually provide a more accurate assessment of the quality of deep inspiration breath-hold (DIBH) and patient movement during tangential breast radiotherapy (RT). A system was developed to measure two geometrical parameters, the lung depth (LD) and the irradiated width (named here skin distance, SD), along three user-selected lines in MV EPID images of breast tangents. The purpose of this study was to test the system during tangential breast RT with DIBH. Materials and methods: Measurements of LDs and SDs were carried out in real time. DIBH was guided with a commercial system using a marker block. Results from 17 patients were assessed. Mean midline LDs, , per tangent were compared to the planned mLDs; differences between the largest and smallest observed () per tangent were calculated. Results: For 56% (162/288) of the tangents tested, were outside the tolerance window. All but one patient had at least one fraction showing this behaviour. The largest difference found between an and its planned mLD was −16.9 mm. The accuracy of patient positioning and the quality of marker-block-based DIBH guidance contributed to the differences. Fractions with patient position verification using a single EPID image taken before treatment showed a lower rate (34%), suggesting reassessment of setup procedures. Conclusions: Real-time treatment monitoring of the internal anatomy during DIBH delivery of tangential breast RT is feasible and useful. The new system requires no additional radiation for the patient.
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- 2022
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14. Evaluation of bactericidal effects of silver hydrosol nanotherapeutics against Enterococcus faecium 1449 drug resistant biofilms
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Alya Limayem, Mausam Mehta, Natalie Kondos, Divya Kaushal, Farhat Binte Azam, Sriram Chellappan, Nan Qin, and Qingyu Zhou
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multi-drug resistance ,E. faecium ,bioactive silver hydrosol nanoparticles ,bactericidal treatment ,cytotoxicity ,artificial intelligence ,Microbiology ,QR1-502 - Abstract
IntroductionSilver (Ag) nanoparticles (NPs) are well documented for their broad-spectrum bactericidal effects. This study aimed to test the effect of bioactive Ag-hydrosol NPs on drug-resistant E. faecium 1449 strain and explore the use of artificial intelligence (AI) for automated detection of the bacteria.MethodsThe formation of E. faecium 1449 biofilms in the absence and presence of Ag-hydrosol NPs at different concentrations ranging from 12.4 mg/L to 123 mg/L was evaluated using a 3-dimentional culture system. The biofilm reduction was evaluated using the confocal microscopy in addition to the Transmission Electronic Microscopy (TEM) visualization and spectrofluorimetric quantification using a Biotek Synergy Neo2 microplate reader. The cytotoxicity of the NPs was evaluated in human nasal epithelial cells using the MTT assay. The AI technique based on Fast Regional Convolutional Neural Network architecture was used for the automated detection of the bacteria.ResultsTreatment with Ag-hydrosol NPs at concentrations ranging from 12.4 mg/L to 123 mg/L resulted in 78.09% to 95.20% of biofilm reduction. No statistically significant difference in biofilm reduction was found among different batches of Ag-hydrosol NPs. Quantitative concentration-response relationship analysis indicated that Ag-hydrosol NPs exhibited a relative high anti-biofilm activity and low cytotoxicity with an average EC50 and TC50 values of 0.0333 and 6.55 mg/L, respectively, yielding an average therapeutic index value of 197. The AI-assisted TEM image analysis allowed automated detection of E. faecium 1449 with 97% ~ 99% accuracy.DiscussionConclusively, the bioactive Ag-hydrosol NP is a promising nanotherapeutic agent against drug-resistant pathogens. The AI-assisted TEM image analysis was developed with the potential to assess its treatment effect.
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- 2023
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15. The trauma bubble: patient and family experience of serious burn injury
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Natalie Ko, Janice Gullick, Rae A. Johnston, and Susan Taggart
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Adult ,Male ,Burn injury ,medicine.medical_specialty ,Best practice ,media_common.quotation_subject ,Interviews as Topic ,Emotional distress ,medicine ,Humans ,Family ,Psychiatry ,Qualitative Research ,media_common ,business.industry ,Rehabilitation ,Australia ,Pain management ,Middle Aged ,medicine.disease ,Emotional trauma ,Distress ,Emergency Medicine ,Surgery ,Grief ,Female ,Medical emergency ,business ,Burns ,Qualitative research - Abstract
The aim of this study was to understand the lived experience of burn injury for Australian patients and families. Of specific interest was the period covering emergency and inhospital care and early experiences of transition into the community. Eighteen participants including patients with serious burn injury and close family members engaged in indepth, semistructured interviews. Data were analysed using Heideggerian phenomenology and were interpreted within the framework of Merleau-Ponty's philosophy of the body. Participants experienced substantial emotional trauma that was unrelated to burn size or severity. Emotional distress was highest amongst people with facial burns. Strong recollections of the accident and poorly managed pain seemed to exacerbate the experience of trauma. Patients described physical otherness, memories of consuming, embodied pain, and recycling of the initial catastrophe. Family members expressed vicarious suffering and were confronted by the physical otherness of their loved one. Participants were isolated in their "bubble of trauma" as they tried to contain grief and loss, and protect loved ones from their distress. Emotional trauma persisted after discharge challenging family functioning and adjustment. These findings support a systematic approach to identifying and responding to the emotional needs of patients and family, including early information about possible emotional reactions to traumatic events and proactive engagement with psychology services. Best practice approaches for early pain management should be a focus for both clinical care and further research.
- Published
- 2014
16. 311 Mental Illness and the Development of Postoperative Atrial Fibrillation in Transcatheter Aortic Valve Replacement Patients: Trends over Time
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Natalie Kolba, Jennifer Morrone, Julia Dokko, Samantha Novotny, Jie Yang, Vineet Tummala, Sohaib Agha, Ashutosh Yaligar, Puja B. Parikh, Aurora D. Pryor, Henry J. Tannous, A. Laurie Shroyer, and Thomas Bilfinger
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Medicine - Abstract
OBJECTIVES/GOALS: The purpose of this retrospective cohort study was to evaluate the impact of mental illness on first-time transcatheter aortic valve replacement (TAVR) and repeat TAVR (viv-AVR) outcomes including postoperative atrial fibrillation (POAF/AFL), as well as trends over time. METHODS/STUDY POPULATION: Using de-identified data reports from the New York Statewide Planning and Research Cooperative System (SPARCS) database from 2005-2018, multivariate logistics models were used to predict endpoints including POAF, the Society of Cardiothoracic surgeon (STS) endpoint (MM), and 30-day readmission (READMIT) in patients with and without mental illness. The TAVR procedure was approved for high-risk patients after 2012, and intermediate-risk patients after 2016, indicting a need to analyze the two populations separately. Multivariate analysis was only conducted on the first-time TAVR patients because of the small n in the viv-TAVR population. RESULTS/ANTICIPATED RESULTS: After 2012, 13.05% (1,810/13,870) of patients undergoing TAVR and 20.83% (15/72) undergoing viv-TAVR were diagnosed with a mental illness before the procedure. After 2016, 15.59% (1,485/9,524) TAVR patients and 20.00% (11/55) viv-TAVR patients had a preoperative diagnosis of mental illness. Multivariate analysis showed that mentally ill patients did not have significant differences in rates of POAF, 30-day readmission, and 30-day composite outcomes when compared to patients without mental illnesses following TAVR procedures after 2012 and 2016. Patients with POAF after both 2012 and 2016 were significantly less likely to be mentally ill, Black, and Hispanic. DISCUSSION/SIGNIFICANCE: Of the mentally ill patients who underwent TAVR, there was no significant difference in short-term outcomes after 2012 vs. 2016, compared to patients without mental illnesses. The small number of mentally ill patients undergoing TAVR may point to provider bias as a contributor to this high selectivity, and further evaluation would be of clinical use.
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- 2023
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17. Intralipid fails to rescue bupivacaine-induced cardiotoxicity in late-pregnant rats
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Caitlin Sherman, Natalie Koons, Michael Zargari, Catherine Cha, Jason Hirsch, Richard Hong, Mansoureh Eghbali, and Soban Umar
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intralipid ,bupivacaine ,cardiotoxicity ,pregnancy ,resuscitation ,Medicine (General) ,R5-920 - Abstract
BackgroundFemales routinely receive bupivacaine for obstetric and regional anesthesia. An accidental overdose of bupivacaine can result in cardiotoxicity and cardiac arrest. Intralipid (ILP) rescues bupivacaine-induced cardiotoxicity in male rats. However, bupivacaine cardiotoxicity and ILP rescue have not been studied in non-pregnant and late-pregnant female rats. Here, we tested the hypothesis that an appropriate dose of ILP would rescue non-pregnant and late-pregnant rats from bupivacaine-induced cardiotoxicity.MethodsNon-pregnant (n = 6) and late-pregnant (n = 7) female rats received intravenous bupivacaine (10-mg/kg bolus) to induce asystole. Resuscitation with 20% ILP (5-ml/kg actual body weight, single bolus, and 0.5-ml/kg/min maintenance) and chest compressions were continued for 10-min. Serial heart rate (HR), left ventricular ejection-fraction (LVEF%), and LV-fractional shortening (LVFS%) were recorded at baseline and 10-min after bupivacaine-induced cardiac arrest. Data are mean ± SD followed by 95% CI. P-values < 0.05 were considered statistically significant.ResultsAll rats developed cardiac arrest within a few seconds after bupivacaine. All non-pregnant rats were successfully rescued by ILP, with a HR of 280 ± 32 bpm at baseline vs. 212 ± 18 bpm at 10-min post ILP (p < 0.01), LVEF of 70 ± 6% vs. 68 ± 5% (p = ns), and LVFS of 41 ± 5% vs. 39 ± 4% (p = ns). Interestingly, 6 out of 7 late-pregnant rats did not recover with ILP. Baseline HR, LVEF and LVFS for late-pregnant rats were 330 ± 40 bpm, 66 ± 5% and 38 ± 4%, respectively. At 10-min post ILP, the HR, LVEF, and LVFS were 39 ± 102 bpm (p < 0.0001), 8 ± 22% (p < 0.0001), and 5 ± 12% (p < 0.001), respectively.ConclusionsILP successfully rescued bupivacaine-induced cardiac arrest in non-pregnant rats, but failed to rescue late-pregnant rats.
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- 2022
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18. Impacts of the COVID-19 Pandemic on Student Learning and Opportunity Gaps Across the 2020–2021 School Year: A National Survey of Teachers
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Jessica M. Namkung, John Marc Goodrich, Michael Hebert, and Natalie Koziol
- Subjects
COVID-19 ,survey research ,elementary school ,academic instruction ,opportunity gaps ,Education (General) ,L7-991 - Abstract
Although many school districts made efforts to provide instruction during the COVID-19 pandemic (including in-person, remote, and blended/hybrid options the length of instruction time and delivery models have varied from district to district. This disruption in education has been projected to result in a significant learning loss, which may be particularly profound for students from disadvantaged backgrounds, leading to widening opportunity gaps. However, there is limited empirical data that can provide important contextual background for understanding the impact of the pandemic on student learning. Therefore, we conducted a national survey with a random sample of 582 elementary school teachers to understand the instructional changes that occurred, the amount of academic content instruction provided to students, and teachers perceptions of the learning supports needed and provided to students during the 2020–2021 school year. Results indicated that most teachers relied on alternative forms of instruction and experienced changes in delivery models but reported low instructional effectiveness. Compared to typical years, teachers reported significant decreases in curriculum coverage; the number of students who received needed interventions, and students who were ready to transition to the next grade level during the 2020–2021 school year. Teachers also reported greater impacts on instruction for students from disadvantaged backgrounds. Follow-up analyses using prior school achievement data corroborated the findings that higher school achievement was associated with smaller impacts on student learning and delivery of instruction.
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- 2022
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19. Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation
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Thomas Yul Avery, Natalie Köhler, Robert Zeiser, Tilman Brummer, and Dietrich Alexander Ruess
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MAPK signaling ,KRAS/BRAF mutations ,targeted inhibition ,tumor immunity ,immune escape ,immunomodulation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Hyperactivation of the RAS-RAF-MEK-ERK cascade - a mitogen-activated protein kinase pathway – has a well-known association with oncogenesis of leading tumor entities, including non-small cell lung cancer, colorectal carcinoma, pancreatic ductal adenocarcinoma, and malignant melanoma. Increasing evidence shows that genetic alterations leading to RAS-RAF-MEK-ERK pathway hyperactivation mediate contact- and soluble-dependent crosstalk between tumor, tumor microenvironment (TME) and the immune system resulting in immune escape mechanisms and establishment of a tumor-sustaining environment. Consequently, pharmacological interruption of this pathway not only leads to tumor-cell intrinsic disruptive effects but also modification of the TME and anti-tumor immunomodulation. At the same time, the importance of ERK signaling in immune cell physiology and potentiation of anti-tumor immune responses through ERK signaling inhibition within immune cell subsets has received growing appreciation. Specifically, a strong case was made for targeted MEK inhibition due to promising associated immune cell intrinsic modulatory effects. However, the successful transition of therapeutic agents interrupting RAS-RAF-MEK-ERK hyperactivation is still being hampered by significant limitations regarding durable efficacy, therapy resistance and toxicity. We here collate and summarize the multifaceted role of RAS-RAF-MEK-ERK signaling in physiology and oncoimmunology and outline the rationale and concepts for exploitation of immunomodulatory properties of RAS-RAF-MEK-ERK inhibition while accentuating the role of MEK inhibition in combinatorial and intermittent anticancer therapy. Furthermore, we point out the extensive scientific efforts dedicated to overcoming the challenges encountered during the clinical transition of various therapeutic agents in the search for the most effective and safe patient- and tumor-tailored treatment approach.
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- 2022
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20. Asian Pacific Society of Cardiology Consensus Statements on the Diagnosis and Management of Obstructive Sleep Apnoea in Patients with Cardiovascular Disease
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Jack Wei Chieh Tan, Leong Chai Leow, Serene Wong, See Meng Khoo, Takatoshi Kasai, Pipin Kojodjojo, Duong-Quy Sy, Chuen Peng Lee, Naricha Chirakalwasan, Hsueh-Yu Li, Natalie Koh, Adeline Tan, Thun How Ong, Aye Thandar Aung, Song Tar Toh, and Chi-Hang Lee
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease (CVD). However, evidence supporting this association in the Asian population is scarce. Given the differences in the epidemiology of CVD and cardiovascular risk factors, as well as differences in the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of OSA in patients with CVD in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of ‘agree’ or ‘neutral.’ The resulting statements provide guidance on the assessment and treatment of OSA in patients with CVD in the Asia-Pacific region. The APSC hopes for these recommendations to pave the way for screening, early diagnosis and treatment of OSA in the Asia-Pacific region.
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- 2022
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21. Management of Contralateral Breast and Axillary Nodes Silicone Migration after Implant Rupture
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Leslie Elahi, MD, Marie-Garance Meuwly, Jean-Yves Meuwly, MD, Wassim Raffoul, MD, PD, MER, and Natalie Koch, MD
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Surgery ,RD1-811 - Abstract
Background:. Silicone implants were developed in 1962 for breast augmentation and became essential in reconstruction after mastectomy. Silicone “bleeding” has been described from both ruptured and intact implants and can induce disseminated granulomatosis due to the component's high fat solubility. If not adequately treated, they can lead to disastrous cosmetic and functional consequences. Because they may mimic malignancy, prompt and reliable diagnosis should be made as early as possible. Methods:. We present a clinical case description of multiple intraparenchymal and ipsi/contralateral intraganglionic siliconomas in a woman who had undergone breast reconstruction, and a literature review of the pathophysiology of siliconomas and their diagnosis and management. Results:. Silicone migration to the contralateral breast and lymph node is rare and has seldom been described. The mechanism is still debated. Excluding malignancy is a priority, and systematic management must be respected to avoid misdiagnosis or unnecessary investigations. Conclusions:. A multidisciplinary approach is essential for siliconoma management. Silicone-related lymphadenopathies do not require follow-up or special treatment unless they interfere with the diagnosis of tumor recurrence. Careful observation is sufficient for asymptomatic siliconomas; however, symptomatic ones should be treated depending on skin involvement and the patient's eligibility for intervention.
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- 2022
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22. Opportunities and challenges of delivering digital clinical trials: lessons learned from a randomised controlled trial of an online behavioural intervention for children and young people
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Charlotte L. Hall, Charlotte Sanderson, Beverly J. Brown, Per Andrén, Sophie Bennett, Liam R. Chamberlain, E. Bethan Davies, Kareem Khan, Natalie Kouzoupi, David Mataix-Cols, Caitlin McKenzie, Tara Murphy, Mark Townsend, Chris Hollis, and Elizabeth Murray
- Subjects
Randomised controlled trials ,Internet ,Online ,Chronic tic disorder ,Tourette syndrome ,Recruitment ,Medicine (General) ,R5-920 - Abstract
Abstract Background Despite being the gold standard of research to determine effectiveness, randomised controlled trials (RCTs) often struggle with participant recruitment, engagement and retention. These issues may be exacerbated when recruiting vulnerable populations, such as participants with mental health issues. We aimed to update understanding of the scope of these problems in trials of health technology and identify possible solutions through reflecting on experiences from an exemplar trial (Online Remote Behavioural Intervention for Tics; ORBIT). Method We extracted anonymised data on recruitment, retention and requests for more funding and time from trials funded by the largest funder of health technology trials in the UK (the National Institute of Health Research Health Technology Assessment) between 2010 and 2020, and compared these with data from a recent, successful trial (ORBIT). ORBIT aimed to assess the clinical- and cost-effectiveness of blended online and human behavioural therapy for tics in young people. Many of the trial procedures, including recruitment, the intervention and data collection, were undertaken online. Results Data were extracted on 51 trials conducted between 2010 and 2020. Sixty per cent of trials failed to reach their original recruitment target and only 44% achieved their follow-up in the specified time frame. In contrast, ORBIT recruited to target and achieved 90% follow-up. We posit that these achievements are related to (a) judicious use of digital technology for trial procedures and (b) adequate numbers of highly trained and motivated trial staff. We provide details of both these to help other research teams plan and cost for successful trials. Conclusion An approach combining human and online methods may be advantageous in facilitating trial delivery, particularly in paediatric mental health services. Given the importance of successful clinical trials in advancing healthcare delivery and the waste of human and economic resources associated with unsuccessfully delivered trials, it is imperative that trials are appropriately costed and future research focusses on improving trial design and delivery. Trial registration The ORBIT trial is registered with ISRTCN ( ISRCTN70758207 ) Registered on March 20, 2018. and ClinicalTrials.gov ( NCT03483493 ). Registered on March 30, 2018.
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- 2020
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23. Notes
- Author
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Natalie Koch
- Published
- 2018
24. 4. From Astana to Asia: Spectacular Cities and the New Capitals of Asia Compared
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Natalie Koch
- Published
- 2018
25. Cover
- Author
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Natalie Koch
- Published
- 2018
26. 3. From Astana to Aral: Making Inequality Enchant in Kazakhstan’s Hinterlands
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Natalie Koch
- Published
- 2018
27. Conclusion: Synecdoche and the Geopolitics of Spectacular Urbanism in Asia
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Natalie Koch
- Published
- 2018
28. Index
- Author
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Natalie Koch
- Published
- 2018
29. 1. Approaching Spectacle Geographically
- Author
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Natalie Koch
- Published
- 2018
30. 2. From Almaty to Astana: Capitalizing the Territory in Kazakhstan
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Natalie Koch
- Published
- 2018
31. Introduction: Spectacular Urbanism and the New Capitals of Asia
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Natalie Koch
- Published
- 2018
32. Acknowledgments
- Author
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Natalie Koch
- Published
- 2018
33. List of Illustrations
- Author
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Natalie Koch
- Published
- 2018
34. Title Page, Copyright, Dedication, Epigraph
- Author
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Natalie Koch
- Published
- 2018
35. Patterns of motivators and barriers to heart health behaviors among adults with behavior-modifiable cardiovascular risk factors: A population-based survey in Singapore.
- Author
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Zijuan Huang, Jien Sze Ho, Qai Ven Yap, Yiong Huak Chan, Swee Yaw Tan, Natalie Koh Si Ya, Lip Ping Low, Huay Cheem Tan, Woon Puay Koh, Terrance Siang Jin Chua, and Sungwon Yoon
- Subjects
Medicine ,Science - Abstract
ObjectivesMotivators and barriers are pivotal factors in the adoption of health behaviors. This study aims to identify patterns of the motivators and barriers influencing heart health behaviors among multi-ethnic Asian adults with behavior-modifiable risk factors for heart disease, namely obesity, physical inactivity and smoking.MethodsA population-based survey of 1,000 participants was conducted in Singapore. Participants were assessed for behavior-modifiable risk factors and asked about motivators and barriers to heart health behaviors. Exploratory and confirmatory factor analyses were conducted to identify factors underlying motivator and barrier question items. Logistic regression was conducted to examine the associations of motivator and barrier factors with sociodemographic characteristics.ResultsThe twenty-five motivator and barrier items were classified into three (outcome expectations, external cues and significant others including family and friends) and four (external circumstances, limited self-efficacy and competence, lack of perceived susceptibility, benefits and intentions and perceived lack of physical capability) factors respectively. Among participants with behavior-modifiable risk factors, those with lower education were more likely to be low in motivation factor of "outcome expectations" and "external cues". The well-educated were more likely to be high in the barrier factor of "lack of perceived susceptibility, benefits and intention" and were less likely to have the motivation factor of "significant others (family or friends)". Those aged 60-75 years had low motivations and high barriers compared to their younger counterparts. Older age was more likely to be low in motivation factor of "outcome expectations" and "external cues" and high in barrier factor of "limited self-efficacy and competence" and "perceived lack of physical capability".ConclusionsFindings underscore the importance of a targeted intervention and communication strategy addressing specific motivation and barrier factors in different population segments with modifiable risk factors.
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- 2022
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36. AgTech in Arabia: 'spectacular forgetting' and the technopolitics of greening the desert
- Author
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Natalie Koch
- Subjects
Environmental sciences ,GE1-350 ,Political science - Abstract
'AgTech' is the latest discourse about introducing new technologies to agricultural production. Researchers, corporations, and governments around the world are investing heavily in supporting its development. Abu Dhabi, the largest and wealthiest emirate in the UAE, has been among these supporters, recently announcing a massive scheme to support AgTech companies. Given the extreme temperatures and aridity of the Arabian Peninsula, several new start-ups have focused on 'controlled environment' facilities – hydroponics and aeroponics in various kinds of greenhouses. Despite the narrative of novelty touted by these companies, this is not the UAE's first foray with bringing ultra-modern or 'scientific' greenhouses to the Arabian Peninsula – a large University of Arizona project did so in Abu Dhabi from 1969-1974. Yet that project is largely forgotten today, including among today's new AgTech entrepreneurs. This article investigates why this is the case and, more generally, why the systematic failures of high-modernist, spectacular projects like those to green the desert are so routinely forgotten. In analyzing the story linking AgTech in Arabia 50 years ago and today, I show how 'spectacular forgetting' is related to the technopolitics of spectacle, but also rooted in geopolitical discourses and spatial imaginaries particular to each historical moment. Keywords: spectacle; desert greening; AgTech; agriculture; Arabian Peninsula; United Arab Emirates
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- 2019
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37. Asian Pacific Society of Cardiology Consensus Recommendations on Dyslipidaemia
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Natalie Koh, Brian A Ference, Stephen J Nicholls, Ann Marie Navar, Derek P Chew, Karam Kostner, Ben He, Hung Fat Tse, Jamshed Dalal, Anwar Santoso, Junya Ako, Hayato Tada, Jin Joo Park, Mei Lin Ong, Eric Lim, Tavin Subramaniam, Yi-Heng Li, Arintaya Phrommintikul, SS Iyengar, Saumitra Ray, Kyung Woo Park, Hong Chang Tan, Narathip Chunhamaneewat, Khung Keong Yeo, and Jack Wei Chieh Tan
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The prevalence of dyslipidaemia has been increasing in the Asia-Pacific region and this is attributed to dietary changes and decreasing physical activity. While there has been substantial progress in dyslipidaemia therapy, its management in the region is hindered by limitations in awareness, adherence and healthcare costs. The Asian Pacific Society of Cardiology (APSC) developed these consensus recommendations to address the need for a unified approach to managing dyslipidaemia. These recommendations are intended to guide general cardiologists and internists in the assessment and treatment of dyslipidaemia and are hoped to pave the way for improving screening, early diagnosis and treatment. The APSC expert panel reviewed and appraised the evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed, which were then put to an online vote. The resulting consensus recommendations tackle contemporary issues in the management of dyslipidaemia, familial hypercholesterolaemia and lipoprotein(a) in the Asia-Pacific region.
- Published
- 2021
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38. Clinical Characteristics, Management, and Outcomes of Cancer Patients With Coronavirus Disease 2019 Admitted to the ICU
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Michael K. M. Dang, MD, Isha Bhatt, MD, Alina O. Dulu, MD, Hao Zhang, MD, Natalie Kostelecky, RN, and Stephen M. Pastores, MD
- Subjects
Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
OBJECTIVES:. Adult patients with cancer have a greater likelihood of developing severe illness and death from coronavirus disease 2019 compared with patients without cancer. We sought to characterize the clinical characteristics and outcomes of cancer patients who tested positive for severe acute respiratory syndrome coronavirus 2 and were admitted to the ICU at the peak of the first wave of the pandemic in the United States. DESIGN:. A single-center retrospective cohort study. SETTING:. Two medical-surgical ICUs of a tertiary-care cancer center. PATIENTS/SUBJECTS:. All consecutive adult patients (≥ 18 yr) with current or past (< 2 yr) diagnosis of cancer who were admitted to the ICU with coronavirus disease 2019 between March 1, and June 30, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Demographic, clinical, and laboratory data of 89 critically ill cancer patients were extracted from electronic medical records. Median age was 65 years (interquartile range, 57–70 yr), 66% were White, and 58% male. Approximately a third of patients had three or more comorbidities. Fifty-one patients (57%) had solid tumors, and 38 (42%) had hematologic malignancies. Sixty-one patients (69%) received cancer-directed therapy within the previous 90 days. Sixty patients (67%) required mechanical ventilation, 56% required prone positioning, 28% underwent tracheostomy, and 71% required vasopressors. Hospital mortality was 45% (40/89). Among those who required mechanical ventilation, mortality was 53% (32/60). Hospital mortality was significantly higher among patients with hematologic malignancies, higher severity of illness and organ failure scores, need for invasive mechanical ventilation and vasopressor therapy, lower hemoglobin and platelet count, and higher d-dimer levels at ICU admission. ICU and hospital length of stay were 10 and 26 days, respectively. At 9-month follow-up, the mortality rate was 54% (48/89). CONCLUSIONS:. We report the largest case series and intermediate-term follow-up of cancer patients with coronavirus disease 2019 who were admitted to the ICU. Hospital mortality was 45%. Intermediate-term outcome after hospital discharge was favorable.
- Published
- 2021
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39. Therapeutic targeting of endoplasmic reticulum stress in acute graft-versus-host disease
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Eileen Haring, Geoffroy Andrieux, Franziska M. Uhl, Máté Krausz, Michele Proietti, Barbara Sauer, Philipp R. Esser, Stefan F. Martin, Dietmar Pfeifer, Annette Schmitt-Graeff, Justus Duyster, Natalie Köhler, Bodo Grimbacher, Melanie Boerries, Konrad Aumann, Robert Zeiser, and Petya Apostolova
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Acute graft-versus-host disease (GvHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), a potentially curative treatment for leukemia. Endoplasmic reticulum (ER) stress occurs when the protein folding capacity of the ER is oversaturated. How ER stress modulates tissue homeostasis in the context of alloimmunity is not well understood. We show that ER stress contributes to intestinal tissue injury during GvHD and can be targeted pharmacologically. We observed high levels of ER stress upon GvHD onset in a murine allo- HCT model and in human biopsies. These levels correlated with GvHD severity, underscoring a novel therapeutic potential. Elevated ER stress resulted in increased cell death of intestinal organoids. In a conditional knockout model, deletion of the ER stress regulator transcription factor Xbp1 in intestinal epithelial cells induced a general ER stress signaling disruption and aggravated GvHD lethality. This phenotype was mediated by changes in the production of antimicrobial peptides and the microbiome composition as well as activation of pro-apoptotic signaling. Inhibition of inositol-requiring enzyme 1α (IRE1α), the most conserved signaling branch in ER stress, reduced GvHD development in mice. IRE1α blockade by the small molecule inhibitor 4m8c improved intestinal cell viability, without impairing hematopoietic regeneration and T-cell activity against tumor cells. Our findings in patient samples and mice indicate that excessive ER stress propagates tissue injury during GvHD. Reducing ER stress could improve the outcome of patients suffering from GvHD.
- Published
- 2021
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40. Analysis of the human connectome data supports the notion of a 'Common Model of Cognition' for human and human-like intelligence across domains
- Author
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Andrea Stocco, Catherine Sibert, Zoe Steine-Hanson, Natalie Koh, John E. Laird, Christian J. Lebiere, and Paul Rosenbloom
- Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The Common Model of Cognition (CMC) is a recently proposed, consensus architecture intended to capture decades of progress in cognitive science on modeling human and human-like intelligence. Because of the broad agreement around it and preliminary mappings of its components to specific brain areas, we hypothesized that the CMC could be a candidate model of the large-scale functional architecture of the human brain. To test this hypothesis, we analyzed functional MRI data from 200 participants and seven different tasks that cover a broad range of cognitive domains. The CMC components were identified with functionally homologous brain regions through canonical fMRI analysis, and their communication pathways were translated into predicted patterns of effective connectivity between regions. The resulting dynamic linear model was implemented and fitted using Dynamic Causal Modeling, and compared against six alternative brain architectures that had been previously proposed in the field of neuroscience (three hierarchical architectures and three hub-and-spoke architectures) using a Bayesian approach. The results show that, in all cases, the CMC vastly outperforms all other architectures, both within each domain and across all tasks. These findings suggest that a common set of architectural principles that could be used for artificial intelligence also underpins human brain function across multiple cognitive domains.
- Published
- 2021
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41. Dusky violaceous necrotic plaques of the chest
- Author
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Natalie Kollman, MD, Matthew Franklin, MD, and Arlene Rosenberg, MD
- Subjects
diabetes ,environmental ,fungus ,infections ,infectious diseases ,medical dermatology ,Dermatology ,RL1-803 - Published
- 2020
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42. Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs
- Author
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Tyler C. Beck, Kendra Springs, Jordan E. Morningstar, Catherine Mills, Andrew Stoddard, Lilong Guo, Kelsey Moore, Cortney Gensemer, Rachel Biggs, Taylor Petrucci, Jennie Kwon, Kristina Stayer, Natalie Koren, Jaclyn Dunne, Diana Fulmer, Ayesha Vohra, Le Mai, Sarah Dooley, Julianna Weninger, Yuri Peterson, Patrick Woster, Thomas A. Dix, and Russell A. Norris
- Subjects
MEK1 ,machine learning ,toxicity ,cancer ,drug discovery ,drug development ,Organic chemistry ,QD241-441 - Abstract
Cancer is the second most common cause of death in the United States, accounting for 602,350 deaths in 2020. Cancer-related death rates have declined by 27% over the past two decades, partially due to the identification of novel anti-cancer drugs. Despite improvements in cancer treatment, newly approved oncology drugs are associated with increased toxicity risk. These toxicities may be mitigated by pharmacokinetic optimization and reductions in off-target interactions. As such, there is a need for early-stage implementation of pharmacokinetic (PK) prediction tools. Several PK prediction platforms exist, including pkCSM, SuperCypsPred, Pred-hERG, Similarity Ensemble Approach (SEA), and SwissADME. These tools can be used in screening hits, allowing for the selection of compounds were reduced toxicity and/or risk of attrition. In this short commentary, we used PK prediction tools in the optimization of mitogen activated extracellular signal-related kinase kinase 1 (MEK1) inhibitors. In doing so, we identified MEK1 inhibitors with retained activity and optimized predictive PK properties, devoid of hERG inhibition. These data support the use of publicly available PK prediction platforms in early-stage drug discovery to design safer drugs.
- Published
- 2022
- Full Text
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43. Consensus Recommendations by the Asian Pacific Society of Cardiology: Optimising Cardiovascular Outcomes in Patients with Type 2 Diabetes
- Author
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Jack Wei Chieh Tan, David Sim, Junya Ako, Wael Almahmeed, Mark E Cooper, Jamshed J Dalal, Chaicharn Deerochanawong, David Wei Chun Huang, Sofian Johar, Upendra Kaul, Sin Gon Kim, Natalie Koh, Alice Pik-Shan Kong, Rungroj Krittayaphong, Bernard Kwok, Bien J Matawaran, Quang Ngoc Nguyen, Loke Meng Ong, Jin Joo Park, Yongde Peng, David KL Quek, Ketut Suastika, Norlela Sukor, Boon Wee Teo, Chee Kiang Teoh, Jian Zhang, Eugenio B Reyes, and Su Yen Goh
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The Asian Pacific Society of Cardiology convened a consensus statement panel for optimising cardiovascular (CV) outcomes in type 2 diabetes, and reviewed the current literature. Relevant articles were appraised using the Grading of Recommendations, Assessment, Development and Evaluation system, and consensus statements were developed in two meetings and were confirmed through online voting. The consensus statements indicated that lifestyle interventions must be emphasised for patients with prediabetes, and optimal glucose control should be encouraged when possible. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are recommended for patients with chronic kidney disease with adequate renal function, and for patients with heart failure with reduced ejection fraction. In addition to SGLT2i, glucagon-like peptide-1 receptor agonists are recommended for patients at high risk of CV events. A blood pressure target below 140/90 mmHg is generally recommended for patients with type 2 diabetes. Antiplatelet therapy is recommended for secondary prevention in patients with atherosclerotic CV disease.
- Published
- 2021
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44. The Role of Immune Checkpoint Molecules for Relapse After Allogeneic Hematopoietic Cell Transplantation
- Author
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Natalie Köhler, Dietrich Alexander Ruess, Rebecca Kesselring, and Robert Zeiser
- Subjects
allogeneic hematopoietic cell transplantation ,immune checkpoint ,immune checkpoint inhibitor ,anti-PD-1 ,graft-versus-host disease ,graft-versus-leukemia ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Immune checkpoint molecules represent physiological brakes of the immune system that are essential for the maintenance of immune homeostasis and prevention of autoimmunity. By inhibiting these negative regulators of the immune response, immune checkpoint blockade can increase anti-tumor immunity, but has been primarily successful in solid cancer therapy and Hodgkin lymphoma so far. Allogeneic hematopoietic cell transplantation (allo-HCT) is a well-established cellular immunotherapy option with the potential to cure hematological cancers, but relapse remains a major obstacle. Relapse after allo-HCT is mainly thought to be attributable to loss of the graft-versus-leukemia (GVL) effect and hence escape of tumor cells from the allogeneic immune response. One potential mechanism of immune escape from the GVL effect is the inhibition of allogeneic T cells via engagement of inhibitory receptors on their surface including PD-1, CTLA-4, TIM3, and others. This review provides an overview of current evidence for a role of immune checkpoint molecules for relapse and its treatment after allo-HCT, as well as discussion of the immune mediated side effect graft-vs.-host disease. We discuss the expression of different immune checkpoint molecules on leukemia cells and T cells in patients undergoing allo-HCT. Furthermore, we review mechanistic insights gained from preclinical studies and summarize clinical trials assessing immune checkpoint blockade for relapse after allo-HCT.
- Published
- 2021
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45. 281 A Knowledge Chasm: Preoperative Mental Illness Impact on New Onset Postoperative Atrial Fibrillation
- Author
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Natalie Kolba, Anne Laurie W. Shroyer, and Thomas Bilfinger
- Subjects
Medicine - Abstract
OBJECTIVES/GOALS: To date, no reviews have been published combining the topics of pre-operative mental illness and postoperative atrial fibrillation (POAF). For adult cardiac surgical procedures, therefore, this scoping review provides an overview of the published evidence for this novel topic. METHODS/STUDY POPULATION: A combination of MESH terms and text words were used to capture all papers analyzing any risk factors for atrial fibrillation development after any cardiovascular surgery, and thus, 4,203 search results were initially identified. Papers were manually screened for relevance, resulting in 69 articles that analyzed risk factors associated with POAF. As a separate analytical step, all included publications were used to identify additional citations and Web of Science PubMed identification number-based (i.e., PMID) specific backwards citation searches were performed to ensure comprehensive coverage. For each of the three articles analyzed, moreover, these PMIDs were further evaluated using individual google scholar searches to assure no other relevant literature was inadvertently found. RESULTS/ANTICIPATED RESULTS: For the 69 relevant articles found with multivariable risk models predicting new onset POAF during this scoping review, a wide variety of patient risk factors were reported. The statistically significant predictors reported for new POAF included age (57 papers), hypertension (22 papers), tobacco use (15 papers), LVEF-related characteristics (14 papers), COPD (13 papers), and patient gender (13 papers). All other factors were found to be significant 10 times or fewer; importantly, no multivariable models evaluated mental illness-related factors as predictors of new onset POAF. Only 3 articles even considered the potential influence of mental illnesses. DISCUSSION/SIGNIFICANCE: Mentally ill patients have been documented to have increased incidence of cardiovascular disease and adverse cardiac outcomes, however, very few articles evaluated mental illness associations with POAF. This comprehensive review has demonstrated the urgent need for new research focused on mental illness impacts.
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- 2022
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46. Food Allergen Nitration Enhances Safety and Efficacy of Oral Immunotherapy in Food Allergy
- Author
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Nazanin Samadi, Larissa Koidl, Martina Salzmann, Martina Klems, Natalie Komatitsch, Denise Schaffer, Eleonore Weidmann, Albert Duschl, Jutta Horejs-Hoeck, and Eva Untersmayr
- Subjects
oral immunotherapy ,food allergy ,protein nitration ,modulated immune response ,Nutrition. Foods and food supply ,TX341-641 - Abstract
(1) Background: Posttranslational protein modifications have been demonstrated to change protein allergenicity. Previously, it was reported that pretreatment with highly nitrated food proteins induced a tolerogenic immune response in an experimental mouse model and in human immune cells. Here, we investigated a possible therapeutic effect of modified proteins and evaluated the safety of oral exposure to highly nitrated proteins in an experimental food allergy model. (2) Methods: BALB/c mice were orally sensitized towards ovalbumin (OVA) under gastric acid suppression. Thereafter, treatment via intragastric gavage with maximally nitrated OVA (nOVAmax) and OVA as a control was performed six times every 2 weeks. On the last day of experiments, all the treated mice were orally challenged with OVA. Systemic anaphylactic reaction was determined by measuring the core body temperature. Moreover, antibody levels, regulatory T cell numbers, cytokine levels and histology of antrum tissues were analyzed. (3) Results: After oral immunotherapy, OVA-specific IgE titers were decreased while IgG1 titers were significantly elevated in the mice receiving OVA. After oral challenge with OVA, nOVAmax-treated allergic animals showed no drop of the core body temperature, which was observed for OVA-allergic and OVA-treated allergic animals. Significantly fewer eosinophils and mast cells were found in the gastric mucosa of the allergic mice after nOVAmax treatment. (4) Conclusions: Oral immunotherapy with nOVAmax reduced allergic reactions upon allergen exposure and the number of allergen effector cells in the gastric mucosa. Thus, maximally nitrated allergens enabled an efficient and safe treatment for food allergy in our experimental model.
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- 2022
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47. Current methods and limitations for longitudinal fMRI analysis across development
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Tara Madhyastha, Matthew Peverill, Natalie Koh, Connor McCabe, John Flournoy, Kate Mills, Kevin King, Jennifer Pfeifer, and Katie A. McLaughlin
- Subjects
Neurophysiology and neuropsychology ,QP351-495 - Abstract
The human brain is remarkably plastic. The brain changes dramatically across development, with ongoing functional development continuing well into the third decade of life and substantial changes occurring again in older age. Dynamic changes in brain function are thought to underlie the innumerable changes in cognition, emotion, and behavior that occur across development. The brain also changes in response to experience, which raises important questions about how the environment influences the developing brain. Longitudinal functional magnetic resonance imaging (fMRI) studies are an essential means of understanding these developmental changes and their cognitive, emotional, and behavioral correlates. This paper provides an overview of common statistical models of longitudinal change applicable to developmental cognitive neuroscience, and a review of the functionality provided by major software packages for longitudinal fMRI analysis. We demonstrate that there are important developmental questions that cannot be answered using available software. We propose alternative approaches for addressing problems that are commonly faced in modeling developmental change with fMRI data. Keywords: Longitudinal modeling, Functional magnetic resonance imaging (fMRI), General Linear Model, Structural Equation Modeling, Developmental change
- Published
- 2018
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48. Review of Natalia Kliashtorna. Narodne vbrannia zakhidnoi Boikivshchyny: Litovyshchi ta okolytsi [Folk Clothing of the Western Boiko Region: Litovyshchi and Vicinity].
- Author
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Natalie Kononenko
- Subjects
History of scholarship and learning. The humanities ,AZ20-999 ,Social sciences (General) ,H1-99 - Abstract
Book review of Natalia Kliashtorna. Narodne vbrannia zakhidnoi Boikivshchyny: Litovyshchi ta okolytsi[Folk Clothing of the Western Boiko Region: Litovyshchi and Vicinity]. Translated by Adam Stec' et al., Drukarnia “Foliant,” 2017. 84 pp. Map. Illustrations. Glossaries. Bibliography. $34.95, cloth.
- Published
- 2019
- Full Text
- View/download PDF
49. Proceedings of the 5th Annual United States Army Institute of Surgical Research Summer Undergraduate Research Internship Program 2017
- Author
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Ryan Leone, Katie J. Jensen, Claire Abijay, Troy Dolmetsch, Natalie Koons, Daniel N. Darlington, Andrew P. Cap, Xiaowu Wu, Christopher P. Delavan, Maryanne C. Herzig, Barbara A. Christy, Kelley M. Kempski, August N. Blackburn, Robert A. De Lorenzo, Megan B. Blackburn, Matthew C. Donald, Harold G. Klemcke, Brenna K. Harrington, Celestine J. He, Belinda I. Gómez, Tony Chao, Joshua S. Little, Tiffany C. Heard, Michael A. Dubick, David M. Burmeister, Amy Xu, Kerfoot Walker III, Arezoo Mohammadipoor, Luis Rodriguez, Teryn Roberts, Andriy Batchinsky, Leopoldo Cancio, Ben Antebi, Ryan A. Walford, Colby S. McIntosh, Grantham C. Peltier, Umang Sharma, Robbie K. Montgomery, Michael A. Meledeo, James A. Bynum, Sarah Lovelace, Larry Estlack, Katherine Jensen, Lexi Kazen, Lee C. Mangum, Gerardo R. Garcia, and Kevin S. Akers
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Medicine - Published
- 2017
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50. 99391 A TL1 Team Approach: The Role of Parents in Physical Activity Engagement Among Adolescents with Comorbid Asthma and Obesity
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Jacqlyn Yourell, Natalie Koskela-Staples, David Fedele, and Jennifer Doty
- Subjects
Medicine - Abstract
ABSTRACT IMPACT: Our research highlights the need for both parental and clinical support to promote PA engagement among higher risk youth with comorbid asthma and obesity; these findings will inform research and clinical efforts in the youth development, prevention science, and clinical psychology fields. OBJECTIVES/GOALS: Asthma incidence doubles in youth with obesity. Physical activity (PA) is beneficial for asthma management; however, parental influence on PA levels among youth with asthma and obesity is poorly understood. This study examines the association of parents and PA among youth with asthma and/or obesity, accounting for risk and protective factors. METHODS/STUDY POPULATION: Data from 5th, 8th, 9th, and 11th-graders were obtained from the 2019 Minnesota Student Survey (N=96,820). Linear regressions examined the impact of parent connectedness on PA across 4 groups (neither asthma nor obesity [OB], asthma only, OB only, comorbid asthma/OB). The p-value for significance was set at p.001). Models 2 and 3 added risk factors. Depression was the most salient risk factor, particularly for the highest risk group (asthma/OB; β =-.13, p.001). In Model 4, extracurricular activity involvement (protective factor) was positively associated with PA across all groups (β ranges=: .07-.11, p
- Published
- 2021
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- View/download PDF
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