Medicine and Health Sciences Commons^™

Genotype-Phenotype Diversity Of Beta-Thalassemia In Malaysia: Treatment Options And Emerging Therapies, Maryanne Jin Ai Tan Maryanne

Mary Anne Tan Jin Ai

The haemoglobinopathies and thalassemias represent the most common inherited monogenic disorders in the world1. Beta-thalassaemia major is an ongoing public health problem in Malaysia2. Prior to 2004, the country had no national policy for screening and registry for thalassemia. In the absence of a national audit, the true figure of the extent of thalassemia in the Malaysian population was largely presumptive from micro-mapping studies from various research workers in the country. The estimated carrier rate for beta-thalassemia in Malaysia is 3.5-4%. There were 4768 transfusion dependent thalassemia major patients as of May 2010 (Data from National Thalassemia Registry).

A Novel Totivirus And Piscine Reovirus (Prv) In Atlantic Salmon (Salmo Salar) With Cardiomyopathy Syndrome (Cms), Torstein Tengs

Dr. Torstein Tengs

BACKGROUNDCardiomyopathy syndrome (CMS) is a severe disease affecting large farmed Atlantic salmon. Mortality often appears without prior clinical signs, typically shortly prior to slaughter. We recently reported the finding and the complete genomic sequence of a novel piscine reovirus (PRV), which is associated with another cardiac disease in Atlantic salmon; heart and skeletal muscle inflammation (HSMI). In the present work we have studied whether PRV or other infectious agents may be involved in the etiology of CMS.RESULTSUsing high throughput sequencing on heart samples from natural outbreaks of CMS and from fish experimentally challenged with material from fish diagnosed with CMS …

Selected Hormonal And Neurotransmitter Mechanisms Regulating, James L. Sartin, Joseph A. Daniel, Brian K. Whitlock, Robyn R. Wilborn

Brian K Whitlock, PhD, DVM, DACT

Appetite control is a major issue in normal growth and in suboptimal growth performance settings. A number of hormones, in particular leptin, activate or inhibit orexigenic or anorexigenic neurotransmitters within the arcuate nucleus of the hypothalamus, where feed intake regulation is integrated. Examples of appetite regulatory neurotransmitters are the stimulatory neurotransmitters neuropeptide Y (NPY), agouti-related protein (AgRP), orexin and melanin-concentrating hormone and the inhibitory neurotransmitter, melanocyte-stimulating hormone (MSH). Examination of messenger RNA (using in situ hybridization and realtime PCR) and proteins (using immunohistochemistry) for these neurotransmitters in ruminants has indicated that physiological regulation occurs in response to fasting for several …

Heart And Skeletal Muscle Inflammation Of Farmed Salmon Is Associated With Infection With A Novel Reovirus, Torstein Tengs

Dr. Torstein Tengs

Atlantic salmon (Salmo salar L.) mariculture has been associated with epidemics of infectious diseases that threaten not only local production, but also wild fish coming into close proximity to marine pens and fish escaping from them. Heart and skeletal muscle inflammation (HSMI) is a frequently fatal disease of farmed Atlantic salmon. First recognized in one farm in Norway in 1999, HSMI was subsequently implicated in outbreaks in other farms in Norway and the United Kingdom. Although pathology and disease transmission studies indicated an infectious basis, efforts to identify an agent were unsuccessful. Here we provide evidence that HSMI is associated …

Hydroxyl-Terminated Poly(Urethane Acrylate) As A Soft Liner In Dental Applications: Synthesis And Characterization, Selda Keskin

ABSTRACT: Hydroxyl-terminated poly(urethane acrylate) s were synthesized for use in biomedical applications. Acrylate end capping via an interesterification reaction was successfully achieved with methacryloyl chloride addition to the hydroxyl ends of the polyurethane at low temperatures. 2,4-Toluene diisocyanate, 1,6-hexane diisocyanate, and methylene diphenyl diisocyanate were used as diisocyanates for urethane synthesis, and they were end-capped with methyl methacrylate and hydroxyethyl methacrylate. The nature of the monomers that we used had an effect on the thermal and morphological properties that were interpreted in terms of the level of hydrogen bonding and the degree of phase separation. The synthesized polymers were characterized …

Effect Of Leukemia Inhibitory Factor On Feed Intake And Body Temperature In Sheep, James L. Sartin, D L. Marks, Brian K. Whitlock, Joseph A. Daniel, Barbara P. Steele

Brian K Whitlock, PhD, DVM, DACT

Leukemia inhibitory factor (LIF) has been suggested to function as a potent inhibitor of feed intake in rodents. These studies were designed to determine whether LIF was found in the ovine hypothalamus and whether LIF inhibited feed intake in sheep. Sheep hypothalami were used to clone LIF to indicate presence of the gene in the hypothalamus. The sequence was similar to published data. Another group of sheep were provided intraventricular (ICV) cannulas and injected with doses of LIF at 250, 500, 1000 and 2500 ng per sheep, ICV. Feed intake was inhibited by the 1000 and 2500 ng dose (trt, …

Changes In Plasma Concentrations Of Growth Hormone And Luteinizing Hormone In Ewes Following Central And Peripheral Treatment With Kisspeptin, Brian K. Whitlock, Joseph A. Daniel, Barbara P. Steele, James L. Sartin

Brian K Whitlock, PhD, DVM, DACT

Kisspeptin (KP), a neuroendocrine regulator of gonadotropin releasing hormone, has been hypothesized as an integrator of nutrition and hormones critical to metabolism and regulation of reproduction. Recent evidence suggests growth hormone (GH) secretion may be influenced by KP. The objective of this study was to determine if the GH stimulatory effect of KP is due to actions on the hypothalamus or anterior pituitary gland in ewes. Adult ovariectomized ewes (n=8) were fitted with intracerebroventricular (ICV) cannula to facilitate central administration of experimental treatments. Ewes received one of eight treatments [four intravenously (IV) and four ICV]. Peripheral treatments [0 (Veh), 100, …

Changes In Plasma Concentrations Of Leptin In Ewes During Pregnancy, Joseph A. Daniel, A B. Milam, M E. Gafnea, Brian K. Whitlock, D H. Keisler

Brian K Whitlock, PhD, DVM, DACT

Previous research has demonstrated circulating concentrations of leptin increase in ewes during mid pregnancy then decline in late pregnancy and early lactation. The objective of this study was to more narrowly define the timing of changes in circulating concentrations of leptin with pregnancy in ewes. Katahdin ewes (n= 19) located at latitude 34.275 and longitude -85.183 (Mount Berry, GA) were utilized. Blood samples were collected weekly via jugular veinpuncture beginning immediately before ram exposure on September 23 and continuing until 4 weeks post-lambing. Ewes were exposed to a ram fitted with a marking harness for a 63 day breeding season. …

Non-Prejudiced Detection And Characterization Of Genetic Modifications, Torstein Tengs

Dr. Torstein Tengs

The application of gene technology is becoming widespread much thanks to the rapid increase in technology, resource, and knowledge availability. Consequently, the diversity and number of genetically modified organisms (GMOs) that may find their way into the food chain or the environment, intended or unintended, is rapidly growing. From a safety point of view the ability to detect and characterize in detail any GMO, independent of publicly available information, is fundamental. Pre-release risk assessments of GMOs are required in most jurisdictions and are usually based on application of technologies with limited ability to detect unexpected rearrangements and insertions. We present …

Naı¨Ve T Cells Re-Distribute To The Lungs Of Selectin Ligand Deficient Mice, Thandi M. Onami, John R. Harp

Thandi M. Onami

BACKGROUND: Selectin mediated tethering represents one of the earliest steps in T cell extravasation into lymph nodes via high endothelial venules and is dependent on the biosynthesis of sialyl Lewis X (sLe(x)) ligands by several glycosyltransferases, including two fucosyltransferases, fucosyltransferase-IV and -VII. Selectin mediated binding also plays a key role in T cell entry to inflamed organs. METHODOLOGY/PRINCIPAL FINDINGS: To understand how loss of selectin ligands (sLe(x)) influences T cell migration to the lung, we examined fucosyltransferase-IV and -VII double knockout (FtDKO) mice. We discovered that FtDKO mice showed significant increases (approximately 5-fold) in numbers of naïve T cells in …

Turning Packaging Into Profit, Rihaz Z. Chughatta

Rihaz Z Chughatta

Packaging can be an expensive function to maintain, but it doesn’t have to be. In fact, Packaging can be a source of income for a company. More accurately, what if you took a look at your company’s Profit and Loss and saw Packaging as a negative expense? That’s right, you can turn packaging into profit for your company. How do you accomplish this feat? Glad you asked … read on to find three simple ways to start this process (and satisfy your curiosity) …

Comparison Of Nine Different Real-Time Pcr Chemistries For Qualitative And Quantitative Applications In Gmo Detection, Torstein Tengs

Dr. Torstein Tengs

Several techniques have been developed for detection and quantification of genetically modified organisms, but quantitative real-time PCR is by far the most popular approach. Among the most commonly used realtime PCR chemistries are TaqMan probes and SYBR green, but many other detection chemistries have also been developed. Because their performance has never been compared systematically, here we present an extensive evaluation of some promising chemistries: sequenceunspecific DNA labeling dyes (SYBR green), primer-based technologies (AmpliFluor, Plexor, Lux primers), and techniques involving double-labeled probes, comprising hybridization (molecular beacon) and hydrolysis (TaqMan, CPT, LNA, and MGB) probes, based on recently published experimental data. …

Microtensile Bond Strength Of Self-Adhesive Resin-Based Dental Cement, Selda Keskin

This study investigated the effectiveness of bleaching agents on the micro tensile bond strength (mTBS) of self-adhesive luting cement and enamel. A total of 126 samples were prepared from the labial surfaces of permanent human maxillary central incisors and assigned into three groups with 42 samples each as: control, enamel bleached with 10% hydrogen peroxide (HP), and enamel bleached with 10% carbamide peroxide (CP). Rely X Unicem1 (3 M, ESPE) was used as self-adhesive resin cement. The total testing period for bleaching was selected as 14 days and the bleaching agents were applied 8 hours a day. The statistical one-way …

Manifest Greatness The Final Original Version By Emmanuel Mario B Santos Aka Marc Guerrero, Emmanuel Mario B. Santos Aka Marc Guerrero

Emmanuel Mario B Santos aka Marc Guerrero

MANIFEST GREATNESS vf24jan2010 WE COME TOGETHER THERE OUGHT TO BE NO POOR WE TAKE CHARGE.

Effect Of Au And Au@Ag Core-Shell Nanoparticles On The Sers Of Bridging Organic Molecules., Remziye Guzel Dr., Zafer Ustundag Dr., Haslet Eksi, Selda Keskin Dr., Bilge Taner, Zeynep Durgun, Ali Osman Solak Prof. Dr.

No abstract provided.

An Integrated Modeling Method For Bone Strain Analysis, Daniel Leib, Henry Wang, Eric Dugan

Daniel Leib

No abstract provided.

An Integrated Modeling Method For Tibia Strain Analysis, Daniel Leib, Henry Wang

Daniel Leib

No abstract provided.

Muscular Fatigue Increases Ground Reaction Loading Rate During Walking, Henry Wang, Jeff Frame, Elicia Ozimek, Cara Reedstrom, Daniel Leib, Eric Dugan

Daniel Leib

No abstract provided.

Wavelet-Based Functional Linear Mixed Models: An Application To Measurement Error–Corrected Distributed Lag Models, Elizabeth J. Malloy, Jeffrey S. Morris, Sara D. Adar, Helen Suh, Diane R. Gold, Brent A. Coull

Jeffrey S. Morris

Frequently, exposure data are measured over time on a grid of discrete values that collectively define a functional observation. In many applications, researchers are interested in using these measurements as covariates to predict a scalar response in a regression setting, with interest focusing on the most biologically relevant time window of exposure. One example is in panel studies of the health effects of particulate matter (PM), where particle levels are measured over time. In such studies, there are many more values of the functional data than observations in the data set so that regularization of the corresponding functional regression coefficient …

Members’ Discoveries: Fatal Flaws In Cancer Research, Jeffrey S. Morris

Jeffrey S. Morris

A recent article published in The Annals of Applied Statistics (AOAS) by two MD Anderson researchers—Keith Baggerly and Kevin Coombes—dissects results from a highly-influential series of medical papers involving genomics-driven personalized cancer therapy, and outlines a series of simple yet fatal flaws that raises serious questions about the veracity of the original results. Having immediate and strong impact, this paper, along with related work, is providing the impetus for new standards of reproducibility in scientific research.

Statistical Contributions To Proteomic Research, Jeffrey S. Morris, Keith A. Baggerly, Howard B. Gutstein, Kevin R. Coombes

Jeffrey S. Morris

Proteomic profiling has the potential to impact the diagnosis, prognosis, and treatment of various diseases. A number of different proteomic technologies are available that allow us to look at many proteins at once, and all of them yield complex data that raise significant quantitative challenges. Inadequate attention to these quantitative issues can prevent these studies from achieving their desired goals, and can even lead to invalid results. In this chapter, we describe various ways the involvement of statisticians or other quantitative scientists in the study team can contribute to the success of proteomic research, and we outline some of the …

Informatics And Statistics For Analyzing 2-D Gel Electrophoresis Images, Andrew W. Dowsey, Jeffrey S. Morris, Howard G. Gutstein, Guang Z. Yang

Jeffrey S. Morris

Whilst recent progress in ‘shotgun’ peptide separation by integrated liquid chromatography and mass spectrometry (LC/MS) has enabled its use as a sensitive analytical technique, proteome coverage and reproducibility is still limited and obtaining enough replicate runs for biomarker discovery is a challenge. For these reasons, recent research demonstrates the continuing need for protein separation by two-dimensional gel electrophoresis (2-DE). However, with traditional 2-DE informatics, the digitized images are reduced to symbolic data though spot detection and quantification before proteins are compared for differential expression by spot matching. Recently, a more robust and automated paradigm has emerged where gels are directly …

Bayesian Random Segmentationmodels To Identify Shared Copy Number Aberrations For Array Cgh Data, Veerabhadran Baladandayuthapani, Yuan Ji, Rajesh Talluri, Luis E. Nieto-Barajas, Jeffrey S. Morris

Jeffrey S. Morris

Array-based comparative genomic hybridization (aCGH) is a high-resolution high-throughput technique for studying the genetic basis of cancer. The resulting data consists of log fluorescence ratios as a function of the genomic DNA location and provides a cytogenetic representation of the relative DNA copy number variation. Analysis of such data typically involves estimation of the underlying copy number state at each location and segmenting regions of DNA with similar copy number states. Most current methods proceed by modeling a single sample/array at a time, and thus fail to borrow strength across multiple samples to infer shared regions of copy number aberrations. …

Tuberculosis: An Eight Year (2000-2007) Retrospective Study At The University Of Malaya Medical Centre (Ummc), Kuala Lumpur, Malaysia, Jamaiah Ibrahim

Jamaiah Ibrahim

This was an eight year (2000-2007) retrospective study of tuberculosis in patients admitted to the UMMC. A total of 131 cases were analyzed. Malays constituted the most cases, (43%), followed by Chinese (22%), Indians (17%) and others (18%). The majority of cases were within the 21-60 year old age group, which constituted 69.5% of the total. Males were more commonly affected (65%). Most cases were reported among Malaysians (83%). The majority of patients were unemployed (39%), followed by housewives (10%), laborers (9%), students (8%), shop assistants (7%), and other occupations (27%) The most common presenting complaints were prolonged productive cough, …

Web Based Services In The Library, Nkiru F. Opara Jarlath

Nkiru Opara

Sharing knowledge is power’ as opposed to the old adage that, ‘knowledge is power

Paraoxonase 1 Activity As A Predictor Of Cardiovascular Disease In Type 2 Diabetes, Rozaida @ Poh Yuen Ying

Rozaida @ Poh Yuen Ying

The role of paraoxonase 1 in cardiovascular disease complications in type 2 diabetes mellitus is not fully understood. We studied paraoxonase activity towards paraoxon in 188 non-diabetic and 140 diabetic subjects using general linear models and univariate analysis. Adjusting for age revealed a reduction in activity towards paraoxon was associated with a significant increase in risk (p=0.023) for cardiovascular disease complications in diabetic patients. Multivariate analysis of two plasma measures of paraoxonase activity using paraoxon and diazoxon also showed reduced paraoxonase activity towards paraoxon was associated with a significant increase in risk (p=0.045) for cardiovascular disease complications in diabetic patients. …

Discrete Nonparametric Algorithms For Outlier Detection With Genomic Data, Debashis Ghosh

Debashis Ghosh

In high-throughput studies involving genetic data such as from gene expression mi- croarrays, dierential expression analysis between two or more experimental conditions has been a very common analytical task. Much of the resulting literature on multiple comparisons has paid relatively little attention to the choice of test statistic. In this article, we focus on the issue of choice of test statistic based on a special pattern of dierential expression. The approach here is based on recasting multiple comparisons procedures for assessing outlying expression values. A major complication is that the resulting p-values are discrete; some theoretical properties of sequential testing …

Detecting Outlier Genes From High-Dimensional Data: A Fuzzy Approach, Debashis Ghosh

Debashis Ghosh

A recent nding in cancer research has been the characterization of previously undis- covered chromosomal abnormalities in several types of solid tumors. This was found based on analyses of high-throughput data from gene expression microarrays and motivated the development of so-called `outlier' tests for dierential expression. One statistical issue was the potential discreteness of the test statistics. Using ideas from fuzzy set theory, we develop fuzzy outlier detection algorithms that have links to ideas in multiple comparisons. Two- and K-sample extensions are considered. The methodology is illustrated by application to two microarray studies.

Links Between Analysis Of Surrogate Endpoints And Endogeneity, Debashis Ghosh, Jeremy M. Taylor, Michael R. Elliott

Debashis Ghosh

There has been substantive interest in the assessment of surrogate endpoints in medical research. These are measures which could potentially replace \true" endpoints in clinical trials and lead to studies that require less follow-up. Recent research in the area has focused on assessments using causal inference frameworks. Beginning with a simple model for associating the surrogate and true endpoints in the population, we approach the problem as one of endogenous covariates. An instrumental variables estimator and general two-stage algorithm is proposed. Existing surrogacy frameworks are then evaluated in the context of the model. A numerical example is used to illustrate …

Meta-Analysis For Surrogacy: Accelerated Failure Time Models And Semicompeting Risks Modelling, Debashis Ghosh, Jeremy M. Taylor, Daniel J. Sargent

Debashis Ghosh

There has been great recent interest in the medical and statistical literature in the assessment and validation of surrogate endpoints as proxies for clinical endpoints in medical studies. More recently, authors have focused on using meta-analytical methods for quanti cation of surrogacy. In this article, we extend existing procedures for analysis based on the accelerated failure time model to this setting. An advantage of this approach relative to proportional hazards model is that it allows for analysis in the semi-competing risks setting, where we constrain the surrogate endpoint to occur before the true endpoint. A novel principal components procedure is …