Some Comments on Mapping from Disease-Specific to Generic Health-Related Quality-of-Life Scales

AbstractAn article by Lu et al. in this issue of Value in Health addresses the mapping of treatment or group differences in disease-specific measures (DSMs) of health-related quality of life onto differences in generic health-related quality-of-life scores, with special emphasis on how the mapping is affected by the reliability of the DSM. In the proposed mapping, a factor analytic model defines a conversion factor between the scores as the ratio of factor loadings. Hence, the mapping applies to convert true underlying scales and has desirable properties facilitating the alignment of instruments and understanding their relationship in a coherent manner. It is important to note, however, that when DSM means or differences in mean DSMs are estimated, their mapping is still of a measurement error–prone predictor, and the correct conversion coefficient is the true mapping multiplied by the reliability of the DSM in the relevant sample. In addition, the proposed strategy for estimating the factor analytic mapping in practice requires assumptions that may not hold. We discuss these assumptions and how they may be the reason we obtain disparate estimates of the mapping factor in an application of the proposed methods to groups of patients

Arvutuslikud meetodid DNA koopiaarvu määramiseks

Väitekirja elektrooniline versioon ei sisalda publikatsioone.DNA koopiaarvu variantideks või muutusteks nimetatakse selliseid erinevusi inimeste geneetilises materjalis, mille puhul mingi DNA lõigu koopiaarv on erinev oodatavast koopiaarvust kaks (üks koopia mingit kindlat DNA järjestust emalt päritud kromosoomil ja üks koopia isalt päritud kromosoomil). DNA koopiate vähenemist nimetatakse deletsiooniks ning vastavaid DNA variante nimetatakse deletsioonideks. DNA koopiate juurdetulemist nimetatakse duplitseerumiseks ning selliseid kahest suurema koopiaarvuga variante vastavalt duplikatsioonideks. Antud doktoritöös uuriti inimese DNA koopiaarvu variante, nende seotust erinevate haigustega ja nende tekkimise ja pärandumise eripärasid. Kasutades DNA mikrokiipe ehk geenikiipe uuriti esmalt kas ja millised DNA koopiaarvu muutused võivad olla seotud vaimse arengu mahajäämusega (VAM-ga). Uurides perekondasid, kus ühel või mitmel liikmel oli diagnoositud VAM, leiti mitmeid juba varem VAM-ga seostatud DNA koopiaarvu muutusi ning lisaks leiti ka mitmeid uusi DNA koopiaarvu variante, mille esinemine võib olla seotud VAM-e väljakujunemisega. Sarnane uuring viidi läbi ka korduva spontaanse raseduse katkemise probleemiga paaride ja naiste puhul. Võrreldes nende patsientide gruppi kuuluvate naiste DNA koopiaarvu muutusi ning nende sagedusi terveid emasid sisaldavate kontroll-grupi indiviidide omadega, leiti statistiliselt ja bioloogiliselt oluline erinevus muutunud koopiaarvuga DNA lõigus, mis sisaldab PDZD2 ja GOLPH3 geene ja kus esinevate duplikatsioonide „omamine“ suurendas naistel märkimisväärselt spontaanse raseduse katkemise ohtu. Doktoritöö viimases osas uuriti Tartu Ülikooli Eesti Geenivaramu ja rahvusvahelise HapMap projekti poolt kogutud tõsiste haigusteta inimestel esinevaid DNA koopiaarvu muutusi ja nende pärandumist perekondades. Selle uuringu üheks huvitavamaks tulemuseks oli deletsioonide alapärandumine vanematelt lastele ehk deletsioone kandvaid DNA regioone esines laste genoomides oluliselt vähem, kui normaalse Mendeliaalse (juhusliku) pärandumise korral oleks oodata võinud. Uurides duplikatsioonide regioone perekondades leiti aga, et kaks kolmandikku duplikatsioonides esinevatest DNA koopiatest ei olnud identsed (üksteise täpsed koopiad), vaid mõnevõrra erinevad, demonstreerides seniajani teadmata olnud alleelse varieeruvuse määra DNA duplikatsioonide regioonides.DNA copy number variation is a type of genetic variation in which case the number of copies of a particular region of a chromosome is altered from its normal state. In the non-repetitive portion of the human genome, the normal haploid copy number is one – one copy of each sequence per chromosome. Accordingly, the normal diploid copy number in humans is two – one copy inherited from both parents. A copy number variant (CNV) can result from either a loss of copies (most often called a deletion) or gain of copies (called a duplication or amplification). In this thesis we studied DNA copy number variation in human – how CNVs emerge and how they are inherited from parents to offspring. We also analysed CNVs in the context of few different diseases. By using DNA microarrays we first aimed to determine if CNVs are associated with mental retardation (MR). For this we studied not only index cases with MR but larger nuclear families, where we discovered several already MR-associated CNVs and also a few novel CNV regions that are possibly associated with predisposition to MR. Similar study was conducted in couples and females suffering from recurrent miscarriage. By comparing CNVs and their frequencies in the latter group to these of healthy mothers, we discovered a multi-copy duplication at 5p13.3 that disrupts PDZD2 and GOLPH3 genes and significantly increases maternal risk for pregnancy complications. In the last part of this thesis we studied how CNVs are inherited in Estonian nuclear families (22 trios and 12 families with multiple siblings) and in HapMap Yoruban trios. We determined that deletion-carrying chromosomal regions were observed in the offspring slightly less frequently than expected by random Mendelian inheritance. By analysing duplication-carrying chromosomal regions in these families, we discovered that in two-thirds of such regions the duplicated copies of the underlying DNA sequence were not exactly identical but somewhat different, allowing us to define alternative allelic copies within these copy number gain-carrying chromosomal regions and demonstrating extensive and to-date unmeasured allelic variability in multi-copy CNV regions of the human genome

Exploring Language Learning Experiences of Kurdish and Turkish Asylum Claimants in Canada Through Arts-Informed Research

According to United Nations High Commissioner for Refugees, the highest level of displacement on record was reached in 2019 with 79.5 million people being forced to migrate (United Nations High Commissioner for Refugees, 2020). Although there is a significant influx of asylum seekers arriving in Canada from Turkey, there have been no studies completed in Canada that focus on the experiences of Kurdish and Turkish refugee claimants. Asylum seekers’ lived experiences need to be further investigated because their precarious legal status together with changing governmental policies may limit their access to language education and resettlement programs. Grounded in the arts, this paper analyzes the role of languages and language-learning experiences on Turkish and Kurdish asylum seekers and their integration into Canadian life. Participants were given the opportunity to document their challenges, needs, concerns and successes related to their integration and language-learning experiences by creating different art forms. Analysis of the data is made through the lens of Cooper’s (2011) Bridging Multiple Worlds Theory and Freire’s (1972) concept of critical consciousness. This research will be informative for educators and policy makers involved in the education of young adults from refugee backgrounds

A current perspective on stereotactic body radiation therapy for pancreatic cancer.

Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable) pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT), which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies

Interrater Reliability in Toxicity Identification: Limitations of Current Standards.

PurposeThe National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 is the standard for oncology toxicity encoding and grading, despite limited validation. We assessed interrater reliability (IRR) in multireviewer toxicity identification.Methods and materialsTwo reviewers independently reviewed 100 randomly selected notes for weekly on-treatment visits during radiation therapy from the electronic health record. Discrepancies were adjudicated by a third reviewer for consensus. Term harmonization was performed to account for overlapping symptoms in CTCAE. IRR was assessed based on unweighted and weighted Cohen's kappa coefficients.ResultsBetween reviewers, the unweighted kappa was 0.68 (95% confidence interval, 0.65-0.71) and the weighted kappa was 0.59 (0.22-1.00). IRR was consistent between symptoms noted as present or absent with a kappa of 0.6 (0.66-0.71) and 0.6 (0.65-0.69), respectively.ConclusionsSignificant discordance suggests toxicity identification, particularly retrospectively, is a complex and error-prone task. Strategies to minimize IRR, including training and simplification of the CTCAE criteria, should be considered in trial design and future terminologies

Another method to maintain positive-pressure ventilation through the Montgomery® T tube

We describe airway management in a patient who had a Montgomery® T tube in situ. The main concern pertaining to these patients is the inadequate depth of anaesthesia and ventilation, in view of loss of volume of air and gases, as well as dilution through the proximal end of the Montgomery®  T tube. To circumvent these problems, we describe another method of providing ventilation, through the extraluminal horizontal limb of the Montgomery®  T tube by introducing an uncuffed endotracheal tube and minimising the loss of carrier gases to the larynx, together with a review of literature for the same.Keywords: Montgomery® T tube, positive-pressure ventilationSouth Afr J Anaesth Analg 2013;19(5):274-27

Advances in the Assessment of Climate Change Impact on the Forest Landscape

Changing climates threaten the habitats and ecosystems at variable extents throughout the world. Forests are unique habitats and ecosystems that are vulnerable by the consequences of climate change. The climate change causes disturbances, alterations. and shifting on the forests that can be diagnosed at the tree and stand scales, as well as can be monitored and analyzed at the landscape scale. Furthermore, some recent researches concentrate on conveying the forest tree and stand-level shifting and disturbances to the forest landscape level by upscaling. In this study, the climate change impacts on the forest landscapes; principally, the disturbances including the drought-induced mortality, growth and productivity failures, and insect outbreaks are evaluated. Secondarily, climate change-induced alterations of the forest species distributions and forest landscape compositions, dynamics of the forest biodiversity, and tree migrations are discussed by focusing particularly on the relatively recent advances involving the modeling procedures. Ultimately, monitoring the climate change-driven shifting phenology of the forest landscape through the remote sensing techniques is referred in this study. Moreover, the study examples dependent upon the climate-ecological modeling and satellite data assessment of the forest landscapes throughout the world are also referenced. The landscape-scale assessment of the climate change impacts on the forest ecosystems provides integrated and comprehensive approach toward the proposal of sustainable mitigations and solutions to the phenomenon

It's Not Easy Being Wrong: Evaluating Process of Elimination Reasoning in Large Language Models

Chain-of-thought (COT) prompting can help large language models (LLMs) reason toward correct answers, but its efficacy in reasoning toward incorrect answers is unexplored. This strategy of process of elimination (PoE), when used with COT, has the potential to enhance interpretability in tasks like medical diagnoses of exclusion. Thus, we propose PoE with COT, a new task where LLMs must reason toward incorrect options on multiple-choice questions. We evaluate the ability of GPT-3.5, LLaMA-2, and Falcon to perform PoE with COT on 2-choice commonsense and scientific reasoning datasets. We show that PoE consistently underperforms directly choosing the correct answer. The agreement of these strategies is also lower than the self-consistency of each strategy. To study these issues further, we conduct an error analysis and give suggestions for future work.Comment: In progress preprin

Correlación y asociación entre la actividad física de desplazamiento y calidad de vida en usuarios con enfermedad pulmonar obstructiva crónica pertenecientes al Centro de Salud Familiar Los Castaños de la comuna de La Florida, 2015

Tesis (Kinesiólogo, Licenciado en Kinesiología)En los últimos años, ha aumentado la cifra de usuarios con Enfermedad Pulmonar Obstructiva Crónica (EPOC), tanto a nivel global como nacional. Por lo tanto, resulta primordial evaluar y cuantificar precozmente probables limitaciones en la actividad física y calidad de vida, asociadas a la Enfermedad Pulmonar Obstructiva Crónica (EPOC). Objetivo: Correlacionar y asociar la Actividad física de desplazamiento y Calidad de vida en usuarios con Enfermedad Pulmonar Obstructiva Crónica (EPOC), pertenecientes al Centro de Salud Familiar (CESFAM) Los Castaños, de la comuna de La Florida, en la ciudad de Santiago, Chile. Material y Método: Este estudio es de tipo exploratorio transversal correlacional. La población evaluada es de 8 usuarios con EPOC, 4 hombres y 4 mujeres. Se aplicaron las encuestas Global Physical Activity Questionnaire (GPAQ) para determinar el nivel de actividad física, COPD Assessment Test (CAT) para determinar la calidad de vida, Test de Fagerström, para ver el nivel de adicción física a la nicotina y Alcohol Use Disorders Identification Test (AUDIT) para el nivel de dependencia al alcohol. Además, se utilizaron los programas Data Analysis and Statistical Software (STATA) y Statistical Package for the Social Sciences (SPSS) para el análisis de resultados. Resultados: Se agrupó a los usuarios según cantidad de minutos de desplazamiento diario que realizaban. La mayoría de los usuarios de la muestra calificó como suficientemente activo siendo un 87.5% de la muestra, con más de 21.4 minutos diarios de Actividad física de desplazamiento. La actividad física de desplazamiento se asoció con la calidad de vida (P= 0.018), sin embargo, no se evidenció una correlación entre estas variables Conclusión: Existe una asociación entre la actividad física de desplazamiento y la calidad de vida. Sin embargo, no se evidenció una correlación entre estas variables, evidenciando que se necesitará un mayor número para obtener mejores resultados