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1.
Explor Res Clin Soc Pharm ; 13: 100391, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38174290

ABSTRACT

Background: The novel coronavirus 2019 (COVID-19) pandemic impacted everyday life for most individuals, including students. Unique COVID-19 stressors among students may include virtual learning, mental stress, and being socially distanced from classmates. Studies examining the impact of COVID-19 on stress and lifestyle changes among pharmacy students are limited. Objective: The primary purpose of this study was to compare stress and food or housing insecurity changes associated with COVID-19 in U.S. Doctor of Pharmacy (PharmD) students pre-COVID vs. during-COVID. Methods: A 23-item survey was administered via Qualtrics® to multiple PharmD programs across the U.S. in pre-COVID-19 (spring 2019) and during-COVID-19 (spring 2021). Participants were recruited via e-mail. The survey included questions related to demographics, lifestyle (sleep, exercise, work hours, extracurricular activities), and food and housing insecurities. The survey also included a validated instrument to measure stress (Cohen-Perceived Stress Scale). Results from 2021 were compared to a similar national survey serendipitously administered prior to COVID-19 in Spring 2019. Results: Pre- and COVID-19 analytical cohorts included 278 and 138 participants, respectively. While pre-COVID-19 students were slightly older (29.9 ± 4.7 vs. 27.7 ± 4.2, p ≤0.001), relative to COVID-19 students, other demographic factors were similar. No significant difference was observed in reported stress levels (PSS = 20.0 ± 6.3 vs. 19.7 ± 6.2, p = 0.610) between time periods. Significant differences in food (53.2% vs. 51.4%, p = 0.731) and housing (45.0% vs. 47.1%, p = 0.680) insecurity were also not seen. Conclusions: These findings highlight that PharmD students' perceived stress and food and housing insecurities due to COVID-19 may have been minimal. Additional studies on pharmacy students should be conducted to validate these results. These results may help inform policymakers and stakeholders during the early stages of any future pandemics.

3.
Int J Lab Hematol ; 45(6): 927-934, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37632200

ABSTRACT

INTRODUCTION: Flow cytometry (FCM) is widely used in the diagnosis of mature B-cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B-cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM. METHODS: Cases with a final diagnosis of DLBCL that were analysed by eight-colour FCM were retrospectively collated. Clinical, FCM, histopathological and genetic data were compared between cases detected and cases not detected by FCM. RESULTS: DLBCL cases from 135 different patients were analysed, of which 22 (16%) were not detected by FCM. In samples not detected by flow cytometry, lymphocytes were a lower percentage of total events (p = 0.02), and T cells were a higher percentage of total lymphocytes (p = 0.01). Cases with high MYC protein expression on immunohistochemistry were less likely to be missed by FCM (p = 0.011). Detection of DLBCL was not different between germinal centre B-cell (GCB) and non-GCB subtypes, not significantly affected by the presence of necrosis or fibrosis, and not significantly different between biopsy specimens compared to fine-needle aspirates, or between samples from nodal compared to extranodal tissue. CONCLUSION: The study identifies several factors which affect the likelihood of DLBCL being missed by FCM. Even with eight-colour analysis, FCM fails to detect numerous cases of DLBCL.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Humans , Retrospective Studies , Flow Cytometry , Lymphoma, Large B-Cell, Diffuse/pathology , B-Lymphocytes/pathology , Germinal Center/metabolism , Germinal Center/pathology , Prognosis
4.
BMJ Open ; 12(9): e057187, 2022 09 01.
Article in English | MEDLINE | ID: mdl-36581987

ABSTRACT

INTRODUCTION: Systems science methodologies have been used in attempts to address the complex and dynamic causes of childhood obesity with varied results. This paper presents a protocol for the Reflexive Evidence and Systems interventions to Prevention Obesity and Non-communicable Disease (RESPOND) trial. RESPOND represents a significant advance on previous approaches by identifying and operationalising a clear systems methodology and building skills and knowledge in the design and implementation of this approach among community stakeholders. METHODS AND ANALYSIS: RESPOND is a 4-year cluster-randomised stepped-wedge trial in 10 local government areas in Victoria, Australia. The intervention comprises four stages: catalyse and set up, monitoring, community engagement and implementation. The trial will be evaluated for individuals, community settings and context, cost-effectiveness, and systems and implementation processes. Individual-level data including weight status, diet and activity behaviours will be collected every 2 years from school children in grades 2, 4 and 6 using an opt-out consent process. Community-level data will include knowledge and engagement, collaboration networks, economic costs and shifts in mental models aligned with systems training. Baseline prevalence data were collected between March and June 2019 among >3700 children from 91 primary schools. ETHICS AND DISSEMINATION: Ethics approval: Deakin University Human Research Ethics Committee (HREC 2018-381) or Deakin University's Faculty of Health Ethics Advisory Committee (HEAG-H_2019-1; HEAG-H 37_2019; HEAG-H 173_2018; HEAG-H 12_2019); Victorian Government Department of Education and Training (2019_003943); Catholic Archdiocese of Melbourne (Catholic Education Melbourne, 2019-0872) and Diocese of Sandhurst (24 May 2019). The results of RESPOND, including primary and secondary outcomes, and emerging studies developed throughout the intervention, will be published in the academic literature, presented at national and international conferences, community newsletters, newspapers, infographics and relevant social media. TRIAL REGISTRATION NUMBER: ACTRN12618001986268p.


Subject(s)
Noncommunicable Diseases , Pediatric Obesity , Humans , Child , Pediatric Obesity/prevention & control , Noncommunicable Diseases/prevention & control , Victoria/epidemiology , Health Promotion/methods
5.
J Phys Chem B ; 126(12): 2420-2429, 2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35315675

ABSTRACT

Liquid-liquid extraction (LLE), the go-to process for a variety of chemical separations, is limited by spontaneous organic phase splitting upon sufficient solute loading, called third phase formation. In this study we explore the applicability of critical phenomena theory to gain insight into this deleterious phase behavior with the goal of improving separations efficiency and minimizing waste. A series of samples representative of rare earth purification were constructed to include each of one light and one heavy lanthanide (cerium and lutetium) paired with one of two common malonamide extractants (DMDOHEMA and DMDBTDMA). The resulting postextraction organic phases are chemically complex and often form rich hierarchical structures whose statics and dynamics near the critical point were probed herein with small-angle X-ray scattering and high-speed X-ray photon correlation spectroscopy. Despite their different extraction behaviors, all samples show remarkably similar critical behavior with exponents well described by classical critical point theory consistent with the 3D Ising model, where the critical behavior is characterized by fluctuations with a single diverging length scale. This unexpected result indicates a significant reduction in relevant chemical parameters at the critical point, indicating that the underlying behavior of phase transitions in LLE rely on far fewer variables than are generally assumed. The obtained scalar order parameter is attributed to the extractant fraction of the extractant/diluent mixture, revealing that other solution components and their respective concentrations simply shift the critical temperature but do not affect the nature of the critical fluctuations. These findings point to an opportunity to drastically simplify studies of liquid-liquid phase separation and phase diagram development in general while providing insights into LLE process improvement.

6.
BMJ Qual Saf ; 31(7): 526-540, 2022 07.
Article in English | MEDLINE | ID: mdl-34656982

ABSTRACT

BACKGROUND: Patients and families are important contributors to the diagnostic team, but their perspectives are not reflected in current diagnostic measures. Patients/families can identify some breakdowns in the diagnostic process beyond the clinician's view. We aimed to develop a framework with patients/families to help organisations identify and categorise patient-reported diagnostic process-related breakdowns (PRDBs) to inform organisational learning. METHOD: A multi-stakeholder advisory group including patients, families, clinicians, and experts in diagnostic error, patient engagement and safety, and user-centred design, co-developed a framework for PRDBs in ambulatory care. We tested the framework using standard qualitative analysis methods with two physicians and one patient coder, analysing 2165 patient-reported ambulatory errors in two large surveys representing 25 425 US respondents. We tested intercoder reliability of breakdown categorisation using the Gwet's AC1 and Cohen's kappa statistic. We considered agreement coefficients 0.61-0.8=good agreement and 0.81-1.00=excellent agreement. RESULTS: The framework describes 7 patient-reported breakdown categories (with 40 subcategories), 19 patient-identified contributing factors and 11 potential patient-reported impacts. Patients identified breakdowns in each step of the diagnostic process, including missing or inaccurate main concerns and symptoms; missing/outdated test results; and communication breakdowns such as not feeling heard or misalignment between patient and provider about symptoms, events, or their significance. The frequency of PRDBs was 6.4% in one dataset and 6.9% in the other. Intercoder reliability showed good-to-excellent reliability in each dataset: AC1 0.89 (95% CI 0.89 to 0.90) to 0.96 (95% CI 0.95 to 0.97); kappa 0.64 (95% CI 0.62, to 0.66) to 0.85 (95% CI 0.83 to 0.88). CONCLUSIONS: The PRDB framework, developed in partnership with patients/families, can help organisations identify and reliably categorise PRDBs, including some that are invisible to clinicians; guide interventions to engage patients and families as diagnostic partners; and inform whole organisational learning.


Subject(s)
Ambulatory Care , Benchmarking , Communication , Humans , Patient Reported Outcome Measures , Reproducibility of Results
7.
Int J Lab Hematol ; 44(2): 313-319, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34841680

ABSTRACT

INTRODUCTION: The myelodysplastic syndromes (MDSs) are heterogeneous myeloid malignancies, conventionally diagnosed by cytomorphology and cytogenetics, with an emerging role for flow cytometry. This study compared the performance of a 4-parameter flow cytometry scoring system, the Ogata Score, with other modalities in the diagnosis of MDS. METHODS: Bone marrow aspirate and trephine biopsies from 238 patients performed to assess for possible MDS were analysed, and the flow cytometry score was retrospectively applied. The sensitivity and specificity of the flow cytometry score, the aspirate microscopy, the trephine microscopy with immunohistochemistry, and cytogenetic and molecular results were determined relative to the final diagnosis. RESULTS: The medical records of the 238 patients were reviewed to determine the final clinical diagnosis made at the time of the bone marrow examination. This final diagnosis of MDS, possible MDS or not MDS, was based on clinical features and laboratory tests, including all parameters of the bone marrow investigation, except for the flow cytometry score, which was only determined for this study. The flow cytometry score was 67.4% sensitive and 93.8% specific. Aspirate microscopy had higher sensitivity (83.7%) and similar specificity (92.0%), whereas trephine microscopy had similar sensitivity (66.3%) and specificity (89.4%) to flow cytometry. Although the flow cytometry score had a lower sensitivity than aspirate microscopy, in 18 patients (7.6% of the total) the flow cytometry score was positive for MDS, whereas aspirate microscopy was negative or inconclusive. CONCLUSION: The flow cytometry score and trephine microscopy exhibited reasonable sensitivity and high specificity, and complement aspirate microscopy in the assessment of MDS.


Subject(s)
Myelodysplastic Syndromes , Myeloproliferative Disorders , Flow Cytometry/methods , Humans , Immunophenotyping , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/pathology , Retrospective Studies
8.
Evol Dev ; 23(4): 351-374, 2021 07.
Article in English | MEDLINE | ID: mdl-34382741

ABSTRACT

The capacity to respond to environmental challenges ultimately relies on phenotypic variation which manifests from complex interactions of genetic and nongenetic mechanisms through development. While we know something about genetic variation and structure of many species of conservation importance, we know very little about the nongenetic contributions to variation. Rhizophora mangle is a foundation species that occurs in coastal estuarine habitats throughout the neotropics where it provides critical ecosystem functions and is potentially threatened by anthropogenic environmental changes. Several studies have documented landscape-level patterns of genetic variation in this species, but we know virtually nothing about the inheritance of nongenetic variation. To assess one type of nongenetic variation, we examined the patterns of DNA sequence and DNA methylation in maternal plants and offspring from natural populations of R. mangle from the Gulf Coast of Florida. We used a reduced representation bisulfite sequencing approach (epi-genotyping by sequencing; epiGBS) to address the following questions: (a) What are the levels of genetic and epigenetic diversity in natural populations of R. mangle? (b) How are genetic and epigenetic variation structured within and among populations? (c) How faithfully is epigenetic variation inherited? We found low genetic diversity but high epigenetic diversity from natural populations of maternal plants in the field. In addition, a large portion (up to ~25%) of epigenetic differences among offspring grown in common garden was explained by maternal family. Therefore, epigenetic variation could be an important source of response to challenging environments in the genetically depauperate populations of this foundation species.


Subject(s)
Rhizophoraceae , Animals , DNA Methylation , Ecosystem , Epigenesis, Genetic , Rhizophoraceae/genetics
9.
Phys Rev Lett ; 125(12): 125504, 2020 Sep 18.
Article in English | MEDLINE | ID: mdl-33016761

ABSTRACT

The advent of high-speed x-ray photon correlation spectroscopy now allows the study of critical phenomena in fluids to much smaller length scales and over a wider range of temperatures than is possible with dynamic light scattering. We present an x-ray photon correlation spectroscopy study of critical fluctuation dynamics in a complex fluid typical of those used in liquid-liquid extraction (LLE) of ions, dodecane-DMDBTDMA with extracted aqueous Ce(NO_{3})_{3}. We observe good agreement with both static and dynamic scaling without the need for significant noncritical background corrections. Critical exponents agree with 3D Ising values, and the fluctuation dynamics are described by simple exponential relaxation. The form of the dynamic master curve deviates somewhat from the Kawasaki result, with a more abrupt transition between the critical and noncritical asymptotic behavior. The concepts of critical phenomena thus provide a quantitative framework for understanding the structure and dynamics of LLE systems and a path forward to new LLE processes.

10.
Rev Sci Instrum ; 91(3): 033905, 2020 Mar 01.
Article in English | MEDLINE | ID: mdl-32259998

ABSTRACT

Two dimensional (2D) peak finding is a common practice in data analysis for physics experiments, which is typically achieved by computing the local derivatives. However, this method is inherently unstable when the local landscape is complicated or the signal-to-noise ratio of the data is low. In this work, we propose a new method in which the peak tracking task is formalized as an inverse problem, which thus can be solved with a convolutional neural network (CNN). In addition, we show that the underlying physics principle of the experiments can be used to generate the training data. By generalizing the trained neural network on real experimental data, we show that the CNN method can achieve comparable or better results than traditional derivative based methods. This approach can be further generalized in different physics experiments when the physical process is known.

12.
Zool Stud ; 59: e69, 2020.
Article in English | MEDLINE | ID: mdl-34221145

ABSTRACT

Knowledge of bird species diversity along elevational gradients is key for understanding the distributional limits of species and, ultimately, for promoting measures that conserve biodiversity. In the present study, we evaluated changes in bird species richness, diversity, and endemism along an elevational gradient in the Sierra Madre del Sur in southern Mexico -a globally recognized biodiversity hotspot. Monthly bird surveys were carried out at localities with elevations of 1600, 1800, 2000, and 2200 m over the course of one year (2014-2015) covering an area of 2000 km2 (10 circular plots with a radius of 25 m per elevation site). Diversity was calculated in terms of effective number of species or Hill numbers, while the composition of bird species along the elevational gradient was analyzed by non-metric multidimensional scaling, and endemic bird species turnover was assessed with faunal congruence curves. Overall, a total of 118 bird species belonging to 35 families were recorded along the elevational gradient. Although we found that bird richness and diversity increased with increasing elevation, we also observed significant turnover in bird composition and endemic species, which were likely linked to forest types and conditions, as well as proximity of sites to urban centers. Assessing biodiversity patterns across elevational gradients in a well-recognized biodiversity reservoir advances both understanding of ecological patterns and aids conservation efforts and management of biological resources.

13.
Am J Cardiol ; 123(4): 627-631, 2019 02 15.
Article in English | MEDLINE | ID: mdl-30527769

ABSTRACT

Advanced heart failure (HF) is a devastating chronic illness requiring complex treatment regimens and patient engagement. Having the information, motivation, and skills to live with a medical condition are conceptualized by the term, "activation." Patients referred for advanced HF therapy and their unpaid family caregiver were invited to participate in this study by completing the 10-item patient activation measure (PAM) questionnaire. Anxiety and depression were assessed via the hospital anxiety and depression scale. We compared activation, anxiety, and depression between those selected versus not selected for advanced HF therapy (left ventricular assist device or heart transplantation). We analyzed those who subsequently underwent advanced HF therapy in regards to activation and 1-year survival. There were 133 (68%) patients selected for therapy. Neither depression nor anxiety differed by selection status, but PAM levels did (p = 0.02). Those not selected for therapy were approximately 4 times more likely to have lower activation than those who were selected (8% vs 2%). Of the 133 selected patients, 110 (84%) subsequently underwent advanced HF therapy and 15 (14%) of those died within 1 year. Survival was independent of baseline anxiety (p = 0.92) and depression (p = 0.70), as well as patient and caregiver PAM (p = 0.50 and 0.77, respectively). In conclusion, patients with higher activation were more likely to be selected for advanced HF therapy.


Subject(s)
Heart Failure/psychology , Heart Failure/therapy , Heart Transplantation , Heart-Assist Devices , Patient Participation , Patient Selection , Aged , Anxiety , Caregivers , Chronic Disease , Depression , Female , Health Literacy , Heart Failure/mortality , Humans , Male , Middle Aged , Motivation , Prospective Studies , Referral and Consultation , Surveys and Questionnaires , Survival Rate
14.
Nat Commun ; 9(1): 5296, 2018 12 13.
Article in English | MEDLINE | ID: mdl-30546018

ABSTRACT

Spatial mapping is a promising strategy to investigate the mechanisms underlying the incidence of psychosis. We analyzed a case-cohort study (n = 24,028), drawn from the 1.47 million Danish persons born between 1981 and 2005, using a novel framework for decomposing the geospatial risk for schizophrenia based on locale of upbringing and polygenic scores. Upbringing in a high environmental risk locale increases the risk for schizophrenia by 122%. Individuals living in a high gene-by-environmental risk locale have a 78% increased risk compared to those who have the same genetic liability but live in a low-risk locale. Effects of specific locales vary substantially within the most densely populated city of Denmark, with hazard ratios ranging from 0.26 to 9.26 for environment and from 0.20 to 5.95 for gene-by-environment. These findings indicate the critical synergism of gene and environment on the etiology of schizophrenia and demonstrate the potential of incorporating geolocation in genetic studies.


Subject(s)
Environment , Genetic Predisposition to Disease/genetics , Geography , Schizophrenia/epidemiology , Schizophrenia/genetics , Chromosome Mapping/methods , Denmark/epidemiology , Humans , Proof of Concept Study , Risk Factors
15.
Sci Adv ; 4(9): eaat8355, 2018 09.
Article in English | MEDLINE | ID: mdl-30225369

ABSTRACT

Semiconductors are essential materials that affect our everyday life in the modern world. Two-dimensional semiconductors with high mobility and moderate bandgap are particularly attractive today because of their potential application in fast, low-power, and ultrasmall/thin electronic devices. We investigate the electronic structures of a new layered air-stable oxide semiconductor, Bi2O2Se, with ultrahigh mobility (~2.8 × 105 cm2/V⋅s at 2.0 K) and moderate bandgap (~0.8 eV). Combining angle-resolved photoemission spectroscopy and scanning tunneling microscopy, we mapped out the complete band structures of Bi2O2Se with key parameters (for example, effective mass, Fermi velocity, and bandgap). The unusual spatial uniformity of the bandgap without undesired in-gap states on the sample surface with up to ~50% defects makes Bi2O2Se an ideal semiconductor for future electronic applications. In addition, the structural compatibility between Bi2O2Se and interesting perovskite oxides (for example, cuprate high-transition temperature superconductors and commonly used substrate material SrTiO3) further makes heterostructures between Bi2O2Se and these oxides possible platforms for realizing novel physical phenomena, such as topological superconductivity, Josephson junction field-effect transistor, new superconducting optoelectronics, and novel lasers.

17.
PLoS One ; 12(7): e0181176, 2017.
Article in English | MEDLINE | ID: mdl-28723921

ABSTRACT

IMPORTANCE: Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. OBJECTIVE: Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. MATERIALS AND METHODS: The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. RESULTS: After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). CONCLUSIONS: Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities.


Subject(s)
Bronchopulmonary Dysplasia/prevention & control , Child Development/physiology , Dexamethasone/adverse effects , Glucocorticoids/adverse effects , Hospitalization , Respiration Disorders/chemically induced , Child Development/drug effects , Child, Preschool , Dexamethasone/pharmacology , Dexamethasone/therapeutic use , Female , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Humans , Infant , Infant, Extremely Premature , Infant, Newborn , Male , Pregnancy
18.
Am J Phys Med Rehabil ; 96(12): 843-851, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28644242

ABSTRACT

OBJECTIVE: Children with cerebral palsy may benefit from maintaining a high level of physical fitness similar to typically developing children especially in terms of long-term physical performance, although in practice this is often difficult. The purpose of this study was to determine the effect of participation in sports programs on walking ability and endurance over time. DESIGN: A retrospective cohort study included participants with cerebral palsy, aged 6 to 20 yrs, who attended a summer sports program from 2004 to 2012. There were 256 participant sessions with pre/post data recorded. The participants consisted of a total of 97 children (mean age [SD] = 11.4 [3.1] yrs), many of whom attended multiple programs throughout the years. Programs were held 6 hrs/d, 5 d/wk for up to 4 wks. Outcome measures included the Timed Up and Go, modified 6-min walk, and 25-ft walk/run. RESULTS: The results showed significant improvements in the Timed Up and Go, modified 6-min walk distance and 25-ft walk/run over time. Children in Gross Motor Classification System level III made the largest gains. CONCLUSIONS: Walking ability and endurance seem to improve after participation in an intensive summer sports programs. Higher frequency of program attendance resulted in significant improvements in the Timed Up and Go. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Discuss the importance of physical activity at the participation level (sports programs) for children with cerebral palsy; (2) Contrast the changes in walking ability and endurance for children in Gross Motor Function Classification System level I, II, and III after sports programs; and (3) Identify the impact of higher frequency of sports program attendance over time on walking ability. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.75 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.


Subject(s)
Cerebral Palsy/rehabilitation , Physical Endurance/physiology , Physical Therapy Modalities/organization & administration , Quality of Life , Sports , Walking/physiology , Adolescent , Age Factors , Cerebral Palsy/diagnosis , Child , Cohort Studies , Female , Humans , Male , Patient Participation/statistics & numerical data , Physical Fitness/physiology , Program Evaluation , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Factors , Time Factors , United States , Young Adult
19.
Radiat Res ; 187(6): 743-754, 2017 06.
Article in English | MEDLINE | ID: mdl-28437190

ABSTRACT

Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a ketogenic diet or standard rodent chow, treated with conventionally fractionated radiation (2 Gy/fraction), and tumor growth rates were assessed daily. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based on this and another previously published preclinical study, phase 1 clinical trials in locally advanced NSCLC and pancreatic cancer were initiated, combining standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC) or five weeks (pancreatic cancer). The xenograft experiments demonstrated prolonged survival and increased 4HNE-modfied proteins in animals consuming a ketogenic diet combined with radiation compared to radiation alone. In the phase 1 clinical trial, over a period of three years, seven NSCLC patients enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study and one was withdrawn due to a dose-limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose-limiting toxicity. The preclinical experiments demonstrate that a ketogenic diet increases radiation sensitivity in a pancreatic cancer xenograft model. However, patients with locally advanced NSCLC and pancreatic cancer receiving concurrent radiotherapy and chemotherapy had suboptimal compliance to the oral ketogenic diet and thus, poor tolerance.


Subject(s)
Chemoradiotherapy/methods , Diet Therapy/methods , Diet, Ketogenic/methods , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Pancreatic Neoplasms/therapy , Aged , Aged, 80 and over , Animals , Cell Line, Tumor , Female , Humans , Iowa , Male , Mice , Mice, Nude , Middle Aged , Pancreatic Neoplasms/diagnosis , Treatment Outcome
20.
PLoS One ; 12(1): e0166674, 2017.
Article in English | MEDLINE | ID: mdl-28081118

ABSTRACT

PURPOSE: The direct impact of protracted conflict on population health and development is well understood. However, the extent of a war's impact on long-term health, and the opportunity costs, are less well understood. This research sought to overcome this gap by asking whether or not health outcomes in Sri Lanka would have been better in the absence of a 26-year war than they were in the presence of war. METHODS: A counterfactual model of national and district-level health outcomes was created for Sri Lanka for the period 1982 to 2002. At the national level, the model examined life expectancy, infant mortality rate (IMR), and maternal mortality ratios (MMR). At the district level, it looked at IMR and MMR. The model compared outcomes generated by the counterfactual model to actual obtained health outcomes. It looked at the rate of change and absolute values. RESULTS: The analysis demonstrated that war altered both rate of change and absolute health outcomes for the worse. The impact was most clearly evident at the district level. IMR was poorer than predicted in 10 districts; of these 8 were outside of the conflict zone. The MMR was worse than expected in 11 districts of which 9 were not in the conflict zone. Additionally, the rate of improvement in IMR slowed as a result of war in 16 districts whereas the rate of improvement in MMR slowed in 9. CONCLUSION: This project showed that protracted conflict degraded the trajectory of public health in Sri Lanka and hurt population health outside of the conflict zone. It further provided a novel methodology with which to better understand the indirect impact of conflict on population health by comparing what is to what could have been achieved in the absence of war. In so doing, this research responded to two public health challenges by providing a tool through which to better understand the human and opportunity costs of war and by answering a call for new methodologies.


Subject(s)
Infant Mortality , Life Expectancy , Maternal Mortality , Models, Theoretical , Public Health , Warfare , Female , Humans , Infant , Male , Sri Lanka/epidemiology
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