Qatar Foundation Annual Research Forum Volume 2012 Issue 1

Background: Novel survey instrument development requires reliability testing, but limited information informs the preferred approach in Qatar. The testing of survey characteristics of the Multi-Cultural Assessment Inventory-Qatar (MAI-Q), a novel multicultural assessment tool in Arabic, English, Hindi and Urdu, provided the opportunity to investigate survey distribution procedures. Objective: To determine willingness to participate, and response rates during survey reliability testing by mail and in person. Methodology: To examine participation preferences and rates, patients were recruited through HMC and six primary health centers. When recruited, subjects could choose to take the MAI-Q a second time for the reliability testing in person or by mail. Subjects were either scheduled for follow-up in-person, or were sent the survey in a prepaid, preaddressed envelope. Results: Among 387 subjects who initially took the survey, 177 (46%) declined taking the survey a second time for reliability testing. Of 210 subjects who agreed to take the survey a second time for reliability testing, 145/210 (69%) chose mail, and 65/210 (31%) were offered and chose in person follow-up. Actual follow-up to complete reliability testing was only 29/145 (21%) by post but 40/65 (63%) in person. Conclusion: These findings reveal challenges researchers face when developing and distributing surveys in Qatar. Nearly half of subjects initially recruited were not willing to participate in follow-up testing. Among those agreeing to follow-up testing, the majority chose mail, but only a fifth of them returned instruments. The majority of subjects who chose in person follow up completed testing. These data inform researchers about the tough choices for developing and conducting surveys in Qatar.

Background: In order to monitor the health of new borns , high performance sensors are placed on the body to record information from different organs: nervous system (EEG signals), heartbeat and fetal movement (accelerometer signals). As the received data are non-stationary signals, Quadratic Time-frequency distributions (QTFDs) are often used to represent the energy, temporal and spectral characteristics of these signals. The suitable QTFD should conserve a high resolution and removes the cross-terms artifacts given by inner- and outer- terms. The inner-terms artifacts are observed in mono-component signals. Due to the Quadratic form of the QTFD, outer-terms are added to inner-terms if the signal contains more than one component. Recent QTFDs such as Wigner-Ville distribution, Spectrogram, B distribution, Modified B-Distribution, Choi-Williams, focus on the elimination of outer-terms whereas few works dealt with the inner-terms artifacts. Objectives: This work aims at designing a new kernel that takes into account the presence of both inner-terms and outer-terms artifacts. The proposed QTFD should remove these artifacts while maintaining a high resolution. Methods: A theoretical analysis of the localization of the inner-terms is given. Based on this analysis, we propose first a new kernel that removes the inner-terms for mono-component signal. Multicomponent signals are also considered, in which case we extend the proposed kernel in order to take into account the presence of the outer-terms. Results and conclusion: The resulting TFDs are compared with other methods using several examples of mono-component and multi-component signals. Some real data representing EEG signals and fetal movement are also used. The different simulations indicate that the proposed TFDs are more efficient to the existing ones, leading to potential significant improvement in newborn health outcomes. This work is supported by Qatar National Research Fund, NPRP project No 09-626-2-243

Interprofessional Education (IPE) is defined by the World Health Organization (WHO) as the process by which a group of practicing health-care professionals work together in order to provide promotive, preventive, curative, rehabilitative and other health-related services. WHO strongly encourages efforts to develop and integrate IPE into educational health-care programs for patients' benefits. For this to occur, a set of shared core competencies must be developed and used as a base on which to build and strengthen interprofessional skills in health-care professionals. Little or no research has been made to develop a set of IPE shared core competencies in Qatar. This article describes the method and results of the competency specification process developed by our team. At a first stage, a list of domains with their descriptions were developed using a card-sorting approach. A pyramid model with IPE at the top was also developed. The second stage was to develop the list of shared core competencies related to the domains developed above. The method used was a Delphi-based approach. One of the necessary steps was to draft candidate competencies based on 8 local experts and review of relevant literature. Based on this, feedback from local experts was integrated in an iterative process. The list of competencies was reduced from 20 statements approximately per domain to an average of 6 statements per domain. A rubric was also developed which can be used to evaluate students on the dimensions outlined in the shared core competencies.

Background & Objectives Large-scale proteome analysis by mass spectrometry is commonly preceded by enzymatic digestion of proteins. The conventional protocol for in-solution digest of complex protein mixtures includes trypsin and is performed at room temperature for at least 12h. To improve this time-consuming method we assessed the efficiency of focused ultrasound-assisted enzymatic digest. It has previously been shown that ultrasonication can dramatically reduce digestion time. However, it is not known how this affects protein identification and quantification when applied to complex protein mixtures such as whole cell lysates. Here, we explore in-depth the proteome of embryonic stem cells comparing trypsin-digestion methods with and without ultrasound support side-by-side. Methods In-solution protein digest Protein extracts were digested with sequencing-grade trypsin (Promega) for 1, 5, 10, 20, 30, 40min and 1h in the presence or absence of focused ultrasonication (Covaris). A conventional digestion overnight was included. Reactions were stopped by acidification and heat. Peptides were desalted by reverse phase C18 StageTips. Mass spectrometry Peptides were analyzed on a QExactive (Thermo Scientific) coupled to Easy nLC 1000 (Proxeon). Raw files were processed by MaxQuant v1.3.0.3 software. Peptide searches were performed by Andromeda search engine against the UniProt database. Results and Conclusions Focused ultrasonication clearly enhanced the enzymatic digestion and can be implemented in the daily workflow of mass spectrometry-based proteome analysis.

Introduction: Acute gastroenteritis is a widespread disease that is characterized by diarrhea, vomiting and abdominal pain. It has high morbidity and mortality rate globally. Bacteria, parasites and mostly viruses cause acute gastroenteritis. Most frequent viruses are norovirus, adenovirus, astrovirus and rotavirus. Objectives: To determine the prevalence of the four viruses in the stool samples of patients who were treated at HGH with complaints of acute gastroenteritis. The samples which had been submitted to the microbiology laboratory at HGH, were analyzed by real time-PCR method at Qatar University. The second objective was to compare between ELISA, IMCG and RT-PCR in terms of sensitivity and specificity. Methodology: 288 stool samples and corresponding patients' data were obtained from microbiology laboratory in HMC between 15-Jun-2009 to1-Nov-2009. They were transported to the research lab of biomedical science program- Health Department at Qatar University, where laboratory experiments involving RT-PCR were performed. Statistical analysis was carried out using Excel program. Results: Out of total 288 fecal samples, 131 (45.5%) were positive for the presence of viruses that cause gastroenteritis. Norovirus (28.5%) was the most prevalent, followed by rotavirus (10.4%), adenovirus (6.25%) and astrovirus (0.30%). Conclusion: Norovirus is the most common source of acute gastroenteritis among hospitalized patients, followed by rotavirus. Real time-PCR technique used in this study was found to be more sensitive and specific. By taking RT-PCR as a reference, ELISA and IMCG are found to be similarly low in sensitivity and specificity.

This work presents the development of an algorithm for analyzing ECG waveforms. The identification of the various waveforms on an ECG is the first and most crucial step in any automated analysis. The algorithm developed is capable of detecting all important waveforms. These include the Q,R,S,R' and S' waves, J and ST points and onset and offset of P and T waves. The various techniques utilized in their detection include adaptive thresholding, parabolic curve fitting, modified derivatives and temporal coherence. After detecting the waveforms, various measurements are obtained from the points detected. These include the polarity of the waveforms, the ST elevation, morphology of ST segment, QRS width and T wave morphologies. These measurements can easily be utilized for diagnosing the ECG for various abnormalities. The developed detection and measurement algorithm stands out from previous works in a number of ways. It is comprehensive and capable of detecting all the important ECG waveforms. It works well even on atypical ECG beats with secondary R' and S' waves. The adaptive thresholding approach minimizes the dependence on fixed hard thresholds. The synchronous behavior of ECG recordings across leads is exploited to improve accuracy. The performance of the algorithm was validated on 40 sample 12-lead ECG data of two minutes each. To validate performance on abnormal ECG waveforms, 20 datasets from patients diagnosed for myocardial infarction (MI) were included. An overall detection accuracy of 98.5% was obtained.

Animal models are essential to understand the molecular and cellular basis of human pathologies. The zebrafish has gained significant attention as a novel model system and has several advantages over rodent models, including: (1) genetic and physiological similarity to humans, (2) a high fertility rate, (3) external fertilization, (4) ease of genetic manipulation, (5) enlarging library of heart-specific reporter genes, (6) ability to survive with a dysfunctional heart, (7) transparency enabling powerful imaging modalities. The zebrafish heart has only two chambers but beats with a heart rate comparable to humans. Several genetic models have been engineered, which successfully model cardiac conditions. Random integration of reporter genes by transposon-mediated transgenesis generated a large number of zebrafish lines, specifically labeling different cardiac cell types and tissues. These include marker genes that label the myocardium, epicardium, endocardium, the conduction system, and atrioventricular and aortic valves (see Figure). Such reporter lines are useful to monitor specific cardiac cell populations and to study their role in disease processes. Similar efforts have recently been employed to identify the cell population responsible for cardiac regeneration. Gene mutations identified in humans causing cardiomyopathies have been introduced in zebrafish and successfully modeled the disease process in this species. Moreover, chemical genetic approaches have been successfully employed to identify small molecules, which are able to reverse pathological conditions such as hypertrophic cardiomyopathy. These examples demonstrate the power and versatility of this model organism, which will pave the way for novel therapeutic opportunities to treat cardiovascular disease. In the Qatar Cardiovascular Research Center we plan to utilize the zebrafish model to study the genetic basis of aortic valve disease, hypertrophic cardiomyopathy, and heart failure. A zebrafish lab will be established in Doha as part of the network in order to develop local expertise and to contribute to the overall research efforts.

Progression of colorectal cancer (CRC) culminates in liver metastasis. To identify genes that are involved in the metastatic phenotype, cDNA microarrays were used to analyze mRNA expression profiles of CC531 rat colon adenocarcinoma cells for changes related to their homing into the liver. Briefly, CC531 cells were intraportally implanted into the liver of Wag-Rij rats and re-isolated after 3, 6, 9, 14 and 21 days. Altogether 2919 genes from ca. 25000 genes were deregulated as a response to metastasis formation into the liver. Candidates from promising gene families were chosen for further analysis using different in vitro models and human CRC samples. These gene families included the claudins and the insulin-like growth factor binding proteins (IGFBPs). For claudins, it was shown that the initial phase of rat CRC cell homing into the liver involves a transient down-regulation of several claudins. Also it was shown that siRNA silencing of Cldn1 and Cldn4 increased migration and reduced colony formation, with these phenotypes being consistent with metastatic homing. Correspondingly, human CRC samples showed increased Cldn1 and Cldn4 expression in UICC stages l-lll, and significantly reduced expression in stage IV and in liver metastasis. Additionally, the IHC analysis revealed that the expression of Cldn1, Cldn4 and Cldn3 in liver metastasis specimens was lower than in the corresponding primary carcinomas. Taken together, metastasizing cells require a transient reduction in claudin expression for liberation from the primary tumor and then initialization metastatic growth in the liver. For IGFBPs it was shown that deregulation of IGFBP3 and IGFBP7 is related to the metastatic behavior of CRC cells. In CRC patients, a significant correlation between the expression levels of these genes was noticed but no relation to overall survival was registered. Further, the patients' age was inversely correlated with the expression of IGFBP3. Silencing of IGFBP3 and/or IGFBP7 in human and rat colorectal cancer cell lines reduced proliferation, colony formation, and for IGFBP3, also migration. These results indicate that IGFBP3 and 7 cannot be simply assigned to the group of tumor suppressors, but have additional properties, which become evident only in the context of cancer progression and metastasis formation.

Objectives: There is paucity of data relevant to anticoagulation rates and trends of treatment in patients with atrial fibrillation (AF) in developing countries and whether there are ethnic differences in the utilization of warfarin as some reports have suggested. The aim of this study is to evaluate trends of utilization of warfarin in Arab and South Asian patients hospitalized with AF in a real-world population in a Middle Eastern country. Methods: Retrospective analysis of prospective registry of all patients hospitalized with AF in Qatar from 1991 through 2010 was made. Rate and trends of warfarin use was examined in relation to ethnicity over the years of the study. Results: During the 20 year period; 2857 Arabs and 548 Asians were hospitalized for AF. The mean age of Arabs was 58 years and of Asians 49 years. Overall, 31.8% of Arabs and 39.4% of Asians received warfarin at hospital discharge (p= 0.001). The overall use of warfarin was significantly trending higher from 17 % in the earlier years of the study to 44.1% in the latter years but no differences were found between Arabs and Asians throughout the study period except at the latter years of the study when it was significantly higher in Asians (53% Asians vs. 41.7% Arabs; p= 0.009). Conclusions: Although the trend is significantly increasing over time, warfarin remains underutilized in patients hospitalized with AF irrespective of ethnicity. There is an urgent need for prospective studies to investigate warfarin contraindications, relative warfarin efficacy and bleeding risks in our region to help guide healthcare providers prescribing warfarin and consequently reduce the risk of AF-related disabling strokes.

Background: There is continuing concern about the risk of long-term autograft dilatation and rupture following the Ross procedure. The aim of this study is to characterize the neo-aortic valve in terms of morphology and wall distensibility. Methods: Among 108 Ross patients undergoing yearly echocardiographic assessment in our unit, 17 (16%) had aortic root diameters of >45mm (DG) 14 ± 1 years after operation. In an attempt to characterize the autograft morphology and dynamics, 11 patients (age 47 ± 10) with dilated autografts underwent cardiac multi-slice computed tomography (CT). Dimensions and distensibility of the aortic root were derived from the cine-CT images. Morphological observation was also made with rapid prototyping models based on the multi-slice CT. The patients were compared with 11 age-matched normal controls (C, age 47 ± 9). Results: Sinus diameters (Ds) were increased in DG compared to C (50 ± 3 mm vs 31 ± 4 mm, p < 0.01). The non-coronary sinus of the autograft tended to enlarge to a greater extent than other two sinuses. Aortic diameters (Da) were also increased in DG (35 ± 6 mm vs 28 ± 3 mm, p < 0.01). DG patients had similar cyclic strain (7.2 ± 3.8% vs 8.3 ± 3.6%, p = 0.13) and distensibility (25 ± 14 vs 34 ± 14 MPa-1, p = 0.20). Conclusions: These data support the notion that the autograft root has similar physical properties to the normal aortic root despite significant dilation. This may have implications for both the selection of aortic root substitutes and the clinical management of Ross patients presenting with dilated roots.