Search results for: biostatistics

Authors: Serge Provost, Yishan Zang

Abstract:

Copulas are currently utilized in finance, reliability theory, machine learning, signal processing, geodesy, hydrology and biostatistics, among several other fields of scientific investigation. It follows from Sklar's theorem that the joint distribution function of a multidimensional random vector can be expressed in terms of its associated copula and marginals. Since marginal distributions can easily be determined by making use of a variety of techniques, we address the problem of securing the distribution of the copula. This will be done by using several approaches. For example, we will obtain bivariate least-squares approximations of the empirical copulas, modify the kernel density estimation technique and propose a criterion for selecting appropriate bandwidths, differentiate linearized empirical copulas, secure Bernstein polynomial approximations of suitable degrees, and apply a corollary to Sklar's result. Illustrative examples involving actual observations will be presented. The proposed methodologies will as well be applied to a sample generated from a known copula distribution in order to validate their effectiveness.

Keywords: copulas, Bernstein polynomial approximation, least-squares polynomial approximation, kernel density estimation, density approximation

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Authors: Mohammadreza Mohebbi, Masoumeh Sanagou

Abstract:

The ability to predict clinical outcomes is of great importance to physicians and clinicians. A number of different methods have been used in an effort to accurately predict these outcomes. These methods include the development of scoring systems based on multivariate statistical modelling, and models involving the use of classification and regression trees. The process usually consists of two consecutive phases, namely model development and external validation. The model development phase consists of building a multivariate model and evaluating its predictive performance by examining calibration and discrimination, and internal validation. External validation tests the predictive performance of a model by assessing its calibration and discrimination in different but plausibly related patients. A motivate example focuses on prediction modeling using a sample of patients undergone coronary artery bypass graft (CABG) has been used for illustrative purpose and a set of primary considerations for evaluating prediction model studies using specific quality indicators as criteria to help stakeholders evaluate the quality of a prediction model study has been proposed.

Keywords: clinical prediction models, clinical decision rule, prognosis, external validation, model calibration, biostatistics

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

Abstract:

a systematic observation from a defined time of origin up to certain failure or censor is known as survival data. Survival analysis is a major area of interest in biostatistics and biomedical researches. At the heart of understanding, the most scientific and medical research inquiries lie for a causality analysis. Thus, the main concern of this study is to investigate the causal effect of treatment on survival time conditional to the possibly time-varying covariates. The theory of causality often differs from the simple association between the response variable and predictors. A causal estimation is a scientific concept to compare a pragmatic effect between two or more experimental arms. To evaluate an average treatment effect on survival outcome, the estimating equation was adjusted for time-varying covariates under the semi-parametric transformation models. The proposed model intuitively obtained the consistent estimators for unknown parameters and unspecified monotone transformation functions. In this article, the proposed method estimated an unbiased average causal effect of treatment on survival time of interest. The modified estimating equations of semiparametric transformation models have the advantage to include the time-varying effect in the model. Finally, the finite sample performance characteristics of the estimators proved through the simulation and Stanford heart transplant real data. To this end, the average effect of a treatment on survival time estimated after adjusting for biases raised due to the high correlation of the left-truncation and possibly time-varying covariates. The bias in covariates was restored, by estimating density function for left-truncation. Besides, to relax the independence assumption between failure time and truncation time, the model incorporated the left-truncation variable as a covariate. Moreover, the expectation-maximization (EM) algorithm iteratively obtained unknown parameters and unspecified monotone transformation functions. To summarize idea, the ratio of cumulative hazards functions between the treated and untreated experimental group has a sense of the average causal effect for the entire population.

Keywords: a modified estimation equation, causal effect, semiparametric transformation models, survival analysis, time-varying covariate

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Authors: Gracie Tredget, Raymond McGrath, Karen Ang, Julie Williams, Nick Sevdalis, Fiona Gaughran, Jorge Aria de la Torre, Ioannis Bakolis, Andy Healey, Zarnie Khadjesari, Euan Sadler, Natalia Stepan

Abstract:

Background: Preventable physical health problems have been found to increase morbidity rates amongst adults living with serious mental illness (SMI). Community mental health clinicians have a role in identifying, and preventing physical health problems worsening, and supporting primary care services to administer routine physical health checks for their patients. However, little is known about how mental health staff perceive and approach their role when providing physical healthcare amongst patients with SMI, or the impact these attitudes have on routine practice. Methods: The present study involves a prospective service evaluation specific to Adult Community Mental Health Services at South London and Maudsley NHS Foundation Trust (SLaM). A qualitative methodology will use semi-structured interviews, focus groups and observations to explore attitudes, perceptions and experiences of staff, patients, and carers (n=64) towards physical healthcare, and barriers or facilitators that impact upon it. 1South London and Maudsley NHS Foundation Trust, London, SE5 8AZ, UK 2 Centre for Implementation Science, King’s College London, London, SE5 8AF, UK 3 Psychosis Studies, King's College London, London, SE5 8AF, UK 4 Department of Biostatistics and Health Informatics, King’s College London, London, SE5 8AF, UK 5 Kings Health Economics, King's College London, London, SE5 8AF, UK 6 Behavioural and Implementation Science (BIS) research group, University of East Anglia, Norwich, UK 7 Department of Nursing, Midwifery and Health, University of Southampton, Southampton, UK 8 Mind and Body Programme, King’s Health Partners, Guy’s Hospital, London, SE1 9RT *[email protected] Analysis: Data from across qualitative tasks will be synthesised using Framework Analysis methodologies. Staff, patients, and carers will be invited to participate in co-development of recommendations that can improve routine physical healthcare within Adult Community Mental Health Teams at SLaM. Results: Data collection is underway at present. At the time of the conference, early findings will be available to discuss. Conclusions: An integrated approach to mind and body care is needed to reduce preventable deaths amongst people with SMI. This evaluation will seek to provide a framework that better equips staff to approach physical healthcare within a mental health setting.

Keywords: severe mental illness, physical healthcare, adult community mental health, nursing

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Authors: Iryna P. Dzieciuch, Michael D. Putman

Abstract:

Humidity is known to degrade Navy ship electronic equipment, especially in hot moist environments. If left untreated, it can cause significant and permanent damage. Even rigorous inspection and frequent clean-up would not prevent further equipment contamination and degradation because of the constant presence of favorable growth conditions for many microorganisms. Generally, relative humidity levels of less than 60% will inhibit corrosion in electronic equipment, but because NAVY electronics often operate in hot and humid environments, prevention via dehumidification is not always possible. Currently, there is no defined research that fully describes key mechanisms which cause electronics and its coating degradation. The corrosive action of most bacteria is mainly developed through (i) mycelium adherence to the metal plates, (ii) facilitation the formation of pitting areas, (iii) production of organic acids such as citric, iso-citric, cis-aconitic, alpha-ketoglutaric, which are corrosive to electronic equipment and its components. Our approach studies corrosive action in electronic equipment: circuit-board, wires and connections that are exposed in the humid environment that gets worse during condensation. In our new approach the technical task is built on work with the bacterial communities in public areas, bacterial genetics, bioinformatics, biostatistics and Scanning Electron Microscopy (SEM) of corroded circuit boards. Based on these methods, we collect and examine environmental samples from biofilms of the corroded and non-corroded sites, where bacterial contamination of electronic equipment, such as machine racks and shore boats, is an ongoing concern. Sample collection and sample analysis is focused on addressing the key questions identified above through the following tasks: laboratory sample processing and evaluation under scanning electron microscopy, initial sequencing and data evaluation; bioinformatics and data analysis. Preliminary results from scanning electron microscopy (SEM) have revealed that metal particulates and alloys in corroded samples consists mostly of Tin ( < 40%), Silicon ( < 4%), Sulfur ( < 1%), Aluminum ( < 2%), Magnesium ( < 2%), Copper ( < 1%), Bromine ( < 2%), Barium ( <1%) and Iron ( < 2%) elements. We have also performed X 12000 magnification of the same sites and that proved existence of undisrupted biofilm organelles and crystal structures. Non-corrosion sites have revealed high presence of copper ( < 47%); other metals remain at the comparable level as on the samples with corrosion. We have performed X 1000 magnification on the non-corroded at the sites and have documented formation of copper crystals. The next step of this study, is to perform metagenomics sequencing at all sites and to compare bacterial composition present in the environment. While copper is nontoxic to the living organisms, the process of bacterial adhesion creates acidic environment by releasing citric, iso-citric, cis-aconitic, alpha-ketoglutaric acidics, which in turn release copper ions Cu++, which that are highly toxic to the bacteria and higher order living organisms. This phenomenon, might explain natural “antibiotic” properties that are lacking in elements such as tin. To prove or deny this hypothesis we will use next - generation sequencing (NGS) methods to investigate types and growth cycles of bacteria that from bacterial biofilm the on corrosive and non-corrosive samples.

Keywords: bacteria, biofilm, circuit board, copper, corrosion, electronic equipment, organic acids, tin

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Authors: Mohammed Abdullah Alshahrani

Abstract:

This research focuses on the investigation of partial least squares (PLS) methodology to deal with high-dimensional correlated data. Current developments in technology have enabled experiments to produce data that are characterized by, first, the number of variables that far exceeds the number of observations and, second, variables that are substantially correlated between them. These types of data are commonly found in, first, chemometrics, where absorbance levels of chemical samples are recorded across hundreds of wavelengths in a calibration of a near-infrared (NIR) spectrometer. Second, they are also common to be found in genomics where copy number alterations (CNA) are recorded across thousands of genomic regions from cancer patients. In our study, we investigated key areas to address these challenges. Firstly, we tackled the issue of three main PLS algorithms having potentially different interpretations of relevant quantities. We unified these interpretations by identifying scenarios where all three algorithms yield the same estimates. Secondly, we explored the phenomenon of unusual negative shrinkage factors encountered during PLS model fitting. Unlike ridge regression or principal component regression, where shrinkage factors range between zero and one, PLS can exhibit factors greater than one or even negative, hence more aptly termed ‘filter factors’ rather than ‘shrinkage factors’. This characteristic allows PLS to effectively handle high-dimensional data by applying shrinkage to estimates. To our knowledge, there has been no previous meaningful investigation on the negative filter factors (NFF) in PLS. In this research we present a novel result whereby we identify the condition for NFF to happen and investigate characteristics of the data that are associated with NFF to get an insight. Lastly, the main challenge of the application of PLS is in the interpretation of weights associated with the predictors. With hundreds and thousands of predictors, each and every predictor variable has non-zero weight. However, we expect that only some predictor variables are contributing to the association with the outcome variable. We, therefore, resort to the sparse estimation of predictor weights where some weights are zero estimated and the other weights are non-zero. A (standard) lasso estimation has a weakness in dealing with correlated variables as it picks up one variable within a correlation block without knowing the reason. A novel approach is needed to consider the dependencies between predictor variables in estimating the weights. We propose a new method where a new penalty function is introduced in the likelihood function associated with the estimation of weights. The penalty function is a combination of a lasso penalty that imposes sparsity and a penalty based on Cauchy distribution with a smoother matrix to take into account dependencies between genomic regions. The results show that the estimates of the weights are sparse: many weights are zero estimated, and those non-zero estimates are grouped and exhibit smoothness within them. The interpretation of genomic regions becomes easy, and the identification of important regions for each component can be done simultaneously with prediction in a single modeling framework. We investigate the relation between PLS and graphical modeling using the information in the weights to construct the graph with unsuccessful results. High-dimensional data where the number of predictors (p) exceeds the number of observations (n) are widely used in many applications of regression analysis. Ordinary least squares regression (OLS), which is the most well-known method for regression problems, has less performance with high-dimensional and highly- correlated data. Previous studies have shown that there is an association between copy number alterations (CNA) in some key genes and disease phenotypes. Moreover, it is very important in high-dimensional data to classify the samples into groups, such as tumor types, of gene expression data in bioinformatics and biology. However, the standard regression of classification methods will fail in these cases because the predictors matrix is singular and so, cannot be inverted. Hence, regularised methods are needed such as shrinkage methods and dimension reduction methods. One of the most suggested methods in the literature is partial least squares regression (PLS) for linear regression and classification.

Keywords: negative filter factors, partial least square regression, high-dimensional data, biostatistics, bioinformatics

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