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1.  Primary Stability Recognition of the Newly Designed Cementless Femoral Stem Using Digital Signal Processing 
BioMed Research International  2014;2014:478248.
Stress shielding and micromotion are two major issues which determine the success of newly designed cementless femoral stems. The correlation of experimental validation with finite element analysis (FEA) is commonly used to evaluate the stress distribution and fixation stability of the stem within the femoral canal. This paper focused on the applications of feature extraction and pattern recognition using support vector machine (SVM) to determine the primary stability of the implant. We measured strain with triaxial rosette at the metaphyseal region and micromotion with linear variable direct transducer proximally and distally using composite femora. The root mean squares technique is used to feed the classifier which provides maximum likelihood estimation of amplitude, and radial basis function is used as the kernel parameter which mapped the datasets into separable hyperplanes. The results showed 100% pattern recognition accuracy using SVM for both strain and micromotion. This indicates that DSP could be applied in determining the femoral stem primary stability with high pattern recognition accuracy in biomechanical testing.
PMCID: PMC3988726  PMID: 24800230
2.  Design process of cementless femoral stem using a nonlinear three dimensional finite element analysis 
Minimal available information concerning hip morphology is the motivation for several researchers to study the difference between Asian and Western populations. Current use of a universal hip stem of variable size is not the best option for all femur types. This present study proposed a new design process of the cementless femoral stem using a three dimensional model which provided more information and accurate analysis compared to conventional methods.
This complete design cycle began with morphological analysis, followed by femoral stem design, fit and fill analysis, and nonlinear finite element analysis (FEA). Various femur parameters for periosteal and endosteal canal diameters are measured from the osteotomy level to 150 mm below to determine the isthmus position.
The results showed better total fit (53.7%) and fill (76.7%) canal, with more load distributed proximally to prevent stress shielding at calcar region. The stem demonstrated lower displacement and micromotion (less than 40 μm) promoting osseointegration between the stem–bone and providing primary fixation stability.
This new design process could be used as a preclinical assessment tool and will shorten the design cycle by identifying the major steps which must be taken while designing the femoral stem.
PMCID: PMC3924227  PMID: 24484753
Morphology; Femur; Hip replacement; Cementless hip; Finite element analysis
3.  Geospatial Interpolation and Mapping of Tropospheric Ozone Pollution Using Geostatistics 
Tropospheric ozone (O3) pollution is a major problem worldwide, including in the United States of America (USA), particularly during the summer months. Ozone oxidative capacity and its impact on human health have attracted the attention of the scientific community. In the USA, sparse spatial observations for O3 may not provide a reliable source of data over a geo-environmental region. Geostatistical Analyst in ArcGIS has the capability to interpolate values in unmonitored geo-spaces of interest. In this study of eastern Texas O3 pollution, hourly episodes for spring and summer 2012 were selectively identified. To visualize the O3 distribution, geostatistical techniques were employed in ArcMap. Using ordinary Kriging, geostatistical layers of O3 for all the studied hours were predicted and mapped at a spatial resolution of 1 kilometer. A decent level of prediction accuracy was achieved and was confirmed from cross-validation results. The mean prediction error was close to 0, the root mean-standardized-prediction error was close to 1, and the root mean square and average standard errors were small. O3 pollution map data can be further used in analysis and modeling studies. Kriging results and O3 decadal trends indicate that the populace in Houston-Sugar Land-Baytown, Dallas-Fort Worth-Arlington, Beaumont-Port Arthur, San Antonio, and Longview are repeatedly exposed to high levels of O3-related pollution, and are prone to the corresponding respiratory and cardiovascular health effects. Optimization of the monitoring network proves to be an added advantage for the accurate prediction of exposure levels.
PMCID: PMC3924486  PMID: 24434594
tropospheric ozone (O3); geostatistical analysis; prediction; interpolation; spatial resolution; visualization; Geographical Information Systems (GIS)
4.  Anthropometric Measurements of the Human Distal Femur: A Study of the Adult Malay Population 
BioMed Research International  2013;2013:175056.
The distal femurs of 100 subjects (50 men, 50 women) from the Malay population aged between 19 and 38 years were scanned to measure the anterior-posterior (AP) and medial-lateral (ML) width. The mean AP values were 64.02 ± 3.38 mm and 57.33 ± 3.26 mm for men and women, respectively, and the mean ML values were 74.91 ± 3.52 mm and 64.53 ± 3.07 mm. We compared our data to that published previously for the Chinese and Indian populations. It was found that the Malay population had smaller distal femur than that of the Chinese but was larger than that of the Indian population (P < 0.05). In conclusion, although it is well established that Asians have a smaller distal femur size than that of the Western population, the variations in different Asian ethnicities may need to be considered when designing the appropriate knee implant.
PMCID: PMC3835611  PMID: 24294597
5.  Factors Associated with the Outcome of Open Tibial Fractures 
Although open tibial fractures are common in Malaysia, the outcomes for these patients have not been evaluated in the literature. This retrospective study was conducted to examine the factors associated with infection and non-union in open tibial fractures managed at Hospital Tengku Ampuan Afzan (HTAA), Kuantan, in 2009.
From 1 January until 31 December 2009, the Department of Orthopaedics of HTAA managed 58 patients with open tibial fracture who had a minimum of a one year follow-up period. The median age was 24.5 years (range: 4 to 72 years). The open tibial fractures were graded using the Gustilo open fracture classification as follows: 4 grade I, 21 grade II, 24 grade IIIA and 9 grade IIIB. All open fractures were subjected to a standard treatment protocol at HTAA, which includes the use of prophylactic antibiotics, emergency debridement, fracture stabilisation, wound coverage, and bone reconstruction when required. The mean time from injury to the initial debridement was 29.7 hours (range: 13 to 216 hours).
Seventeen (29%) cases were complicated by infection, and 10 patients (17%) developed non-union. The grade of the open fracture was significantly associated with infection, and age and the time interval between the injury and the initial wound debridement were significantly associated with non-union.
The high rates of infection and non-union, particularly in severe open fractures, indicate that there is a need to improve the management of open tibial fractures treated at HTAA. The time to initial debridement is an important factor that can be readily amended to improve the outcome. Further studies with larger sample sizes are likely needed to replicate and confirm our findings.
PMCID: PMC3957352  PMID: 24643115
assessment; case management; fractures; open; patient outcome; tibia
6.  Analysis of the microRNA transcriptome and expression of different isomiRs in human peripheral blood mononuclear cells 
BMC Research Notes  2013;6:390.
MicroRNAs (miRNAs) have been recognized as one of the key regulatory non-coding RNAs that are involved in a number of basic cellular processes. miRNA expression profiling helps to identify miRNAs that could serve as biomarkers. Next generation sequencing (NGS) platforms provide the most effective way of miRNA profiling, particularly as expression of different isoforms of miRNA (IsomiRs) can be estimated by NGS. Therefore, it is now possible to discern the overall complexity of miRNA populations that participate in gene regulatory networks. It is thus important to consider different isoforms of miRNA as part of total profiling in order to understand all aspects of the biology of miRNAs.
Here next generation sequencing data of small RNAs derived from normal peripheral blood mononuclear cells (PBMC) and Chronic myeloid leukemia (CML) patients has been used to generate miRNA profiles using a computation pipeline which can identify isomiRs that are natural variants of mature miRNAs. IsomiR profiles have been generated for all the 5p and 3p miRNAs (previously known as major mature miRNA and minor or miRNA*) and the data has been presented as a composite total miRNA transcriptome. The results indicated that the most abundant isomiR sequence of about 68% miRNAs, did not match the reference miRNA sequence as entered in the miRBase and that there is a definite pattern in relative concentration of different isomiRs derived from same precursors. Finally, a total of 17 potential novel miRNA sequences were identified suggesting that there are still some new miRNAs yet to be discovered.
Inclusion of different isoforms provides a detailed miRnome of a cell type or tissues. Availability of miRnome will be useful for finding biomarkers of different cell types and disease states. Our results also indicate that the relative expression levels of different isoforms of a miRNA are likely to be dynamic and may change with respect to changes in the cell or differentiation status.
PMCID: PMC3851811  PMID: 24073671
MicroRNA; Next generation sequencing; Normalization; IsomiR; miRnome; Peripheral blood mononuclear cells (PBMC); Chronic myeloid leukemia (CML)
7.  Effectiveness of Platelet Transfusion in Dengue Fever: A Randomized Controlled Trial 
Scientific data regarding effects of platelet transfusion on platelet count in dengue-related thrombocytopenia is scanty.
A single center, randomized non-blinded trial was conducted on adult patients with dengue fever and platelet counts less than 30,000/μl. Patients were randomized to treatment and control group. Treatment group received single donor platelets. Patients with post-transfusion platelet increment (PPI) ≥10,000/μl and/or corrected count increment (CCI) ≥5,000/μl 1 h post-transfusion were considered responders. Primary outcome was platelet count increments at 24 and 72 h.
87 patients were enrolled, and 43 (48.2%) received platelet transfusion. Mean PPI and CCI at 1 h post-transfusion in the treatment group were 18,800/μl and 7,000/μl respectively. 22 (53.6%) patients in the treatment group were non-responders. Mean platelet increments at 24 and 72 h were higher in the treatment group as compared to the control group. Responders showed significantly higher increments when compared to non-responders and the control group at 24 h (p = 0.004 and p ≤ 0.001, respectively) and 72 h (p = 0.001 and p ≤ 0.001, respectively). Significant differences were found between non-responders and the control group at 24 h (p ≤ 0.001), but not at 72 h (p = 0.104). Patients with lower baseline platelet count were more likely to be non-responders. Platelet transfusion neither prevented development of severe bleeding nor shortened time to cessation of bleeding. Three severe transfusion reactions and two deaths occurred in treatment group.
In this trial, almost half the patients showed no response to a high-dose platelet transfusion. Platelet transfusion did not prevent development of severe bleeding or shorten time to cessation of bleeding and was associated with significant side effects. Therefore, platelet transfusion should not be routinely done in the management of dengue fever.
PMCID: PMC3822277  PMID: 24273491
Dengue fever; Dengue hemorrhagic fever; Single donor apheresis platelets; Platelet transfusion; Corrected count increment; CCI; Transfusion reaction
8.  Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment 
BMC Infectious Diseases  2012;12:168.
For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events.
In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART.
A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar.
Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability.
Trial registration
PMCID: PMC3457866  PMID: 22846195
Antiretroviral; Early; Delayed; HIV; Tuberculosis
9.  HIV and Tuberculosis Trends in the United States and Select Sub-Saharan Africa Countries 
Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) are two catastrophic diseases affecting millions of people worldwide every year; and are considered to be pandemic by the World Health Organization. This study aims to compare the recent trends in TB and HIV in the United States and Sub-Saharan African Countries. Data (incidence, prevalence and death rates of HIV and TB) for the United States, Cameroon, Nigeria, and South Africa were collected from The Joint United Nations Programme for HIV/AIDS (UNAIDS), US Census Bureau and World Health Organization (WHO) databases and analyzed using Statistical Analysis Software (SAS v 9.1). Analysis of Variance (ANOVA) was performed to compare the variables of interest between the countries and across time. Results showed that percent rates of TB cases, TB deaths, HIV cases and HIV deaths were significantly different (P < 0.001) among these countries from 1993 to 2006. South Africa had the highest rates of HIV and TB; while US had the lowest rates of both diseases. Tuberculosis and HIV rates for Cameroon and Nigeria were significantly higher when compared to the United States, but were significantly lower when compared to South Africa (P < 0.001). There were significant differences (P < 0.001) in the prevalence of TB and HIV between the United States and the Sub-Saharan African countries, as well as differences within the Sub-Saharan African countries from 1993 to 2006. More analysis needs to be carried out in order to determine the prevalence and incidence of HIV and TB among multiple variables like gender, race, sexual orientation and age to get a comprehensive picture of the trends of HIV and TB.
PMCID: PMC3138039  PMID: 21776244
tuberculosis; HIV; United States; sub-Saharan Africa
10.  Analysis of microRNA transcriptome by deep sequencing of small RNA libraries of peripheral blood 
BMC Genomics  2010;11:288.
MicroRNAs are a class of small non-coding RNAs that regulate mRNA expression at the post - transcriptional level and thereby many fundamental biological processes. A number of methods, such as multiplex polymerase chain reaction, microarrays have been developed for profiling levels of known miRNAs. These methods lack the ability to identify novel miRNAs and accurately determine expression at a range of concentrations. Deep or massively parallel sequencing methods are providing suitable platforms for genome wide transcriptome analysis and have the ability to identify novel transcripts.
The results of analysis of small RNA sequences obtained by Solexa technology of normal peripheral blood mononuclear cells, tumor cell lines K562 and HL60 are presented. In general K562 cells displayed overall low level of miRNA population and also low levels of DICER. Some of the highly expressed miRNAs in the leukocytes include several members of the let-7 family, miR-21, 103, 185, 191 and 320a. Comparison of the miRNA profiles of normal versus K562 or HL60 cells revealed a specific set of differentially expressed molecules. Correlation of the miRNA with that of mRNA expression profiles, obtained by microarray, revealed a set of target genes showing inverse correlation with miRNA levels. Relative expression levels of individual miRNAs belonging to a cluster were found to be highly variable. Our computational pipeline also predicted a number of novel miRNAs. Some of the predictions were validated by Real-time RT-PCR and or RNase protection assay. Organization of some of the novel miRNAs in human genome suggests that these may also be part of existing clusters or form new clusters.
We conclude that about 904 miRNAs are expressed in human leukocytes. Out of these 370 are novel miRNAs. We have identified miRNAs that are differentially regulated in normal PBMC with respect to cancer cells, K562 and HL60. Our results suggest that post - transcriptional processes may play a significant role in regulating levels of miRNAs in tumor cells. The study also provides a customized automated computation pipeline for miRNA profiling and identification of novel miRNAs; even those that are missed out by other existing pipelines. The Computational Pipeline is available at the website:
PMCID: PMC2885365  PMID: 20459673
11.  Toxic Elements in Soil and Groundwater: Short-Time Study on Electrokinetic Removal of Arsenic in the Presence of other Ions 
The electrokinetic technique is an emerging technology presently tested in situ to remove dissolved heavy metals from contaminated groundwater. There is a growing interest for using this system to cleanse clayey soil contaminated by toxic metallic ions. Currently, there are very few available non-destructive treatment methods that could be successfully applied in situ on low permeable type of soil matrix. The main objective of presented study was to validate and possibly enhance the overall efficiency of decontamination by the electrokinetic technique of the low permeable soil polluted by the arsenic in combination with chromium and copper ions. The chosen mixture of ions was imitating leak of pesticide well known as chromate copper arsenate (CCA). The chosen technique is showing a big promise to be used in the future as a portable, easy to install and run on sites with spills or leaks hard to reach otherwise; such as in the dense populated and urbanized areas. Laboratory electrokinetic experiments were designed to understand and possibly manipulate main mechanisms involved during forced migration of ions. All tests were conducted on artificially contaminated kaolinite (low permeable clay soil). Electrokinetic migration was inducted by the low voltage dc current applied through soil column. Series of experiments were designed to assess the efficiency of arsenic-chromium-copper remediation by applying (1) only dc current; and (2) by altering the soil environment. Obtained results showed that arsenic could be successfully removed from the soil in one day (25 hours) span. It was significant time reduction, very important during emergency response. Mass recovered at the end of each test depended on initial condition of soil and type of flushing solution. The best results were obtained, when soil was flushed with either NaOH or NaOCl (total removal efficiency 74.4% and 78.1%, respectively). Direct analysis of remained arsenic in soil after these tests confirmed substantial drop of the initial mass of arsenic in soil profile from 51.54 mg to 10.62 mg (NaOH) and 5.68 mg (NaOCl) after 25 hours of treatment.
PMCID: PMC3807511  PMID: 16823093
Toxic ions; electrokinetic technique; arsenic; CCA; remediation of low permeable soil

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