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1.  Modeling interactions between adjacent nucleosomes improves genome-wide predictions of nucleosome occupancy 
Bioinformatics  2009;25(12):i348-i355.
Motivation: Understanding the mechanisms that govern nucleosome positioning over genomes in vivo is essential for unraveling the role of chromatin organization in transcriptional regulation. Until now, models for predicting genome-wide nucleosome occupancy have assumed that the DNA associations of neighboring nucleosomes on the genome are independent. We present a new model that relaxes this independence assumption by modeling interactions between adjacent nucleosomes.
Results: We show that modeling interactions between adjacent nucleosomes improves genome-wide nucleosome occupancy predictions in an in vitro system that includes only nucleosomes and purified DNA, where the resulting model has a preference for short spacings (linkers) of less than 20 bp in length between neighboring nucleosomes. Since nucleosome occupancy in vitro depends only on properties intrinsic to nucleosomes, these results suggest that the interactions we find are intrinsic to nucleosomes and do not depend on other factors, such as transcription factors and chromatin remodelers. We also show that modeling these intrinsic interactions significantly improves genome-wide predictions of nucleosome occupancy in vivo.
Supplementary information: Supplementary data are available at Bioinformatics online.
PMCID: PMC2687970  PMID: 19478009
2.  ISMB/ECCB 2009 Stockholm 
Bioinformatics  2009;25(12):1570-1573.
The International Society for Computational Biology (ISCB; presents the Seventeenth Annual International Conference on Intelligent Systems for Molecular Biology (ISMB), organized jointly with the Eighth Annual European Conference on Computational Biology (ECCB;, in Stockholm, Sweden, 27 June to 2 July 2009. The organizers are putting the finishing touches on the year's premier computational biology conference, with an expected attendance of 1400 computer scientists, mathematicians, statisticians, biologists and scientists from other disciplines related to and reliant on this multi-disciplinary science. ISMB/ECCB 2009 ( follows the framework introduced at the ISMB/ECCB 2007 ( in Vienna, and further refined at the ISMB 2008 ( in Toronto; a framework developed to specifically encourage increased participation from often under-represented disciplines at conferences on computational biology. During the main ISMB conference dates of 29 June to 2 July, keynote talks from highly regarded scientists, including ISCB Award winners, are the featured presentations that bring all attendees together twice a day. The remainder of each day offers a carefully balanced selection of parallel sessions to choose from: proceedings papers, special sessions on emerging topics, highlights of the past year's published research, special interest group meetings, technology demonstrations, workshops and several unique sessions of value to the broad audience of students, faculty and industry researchers. Several hundred posters displayed for the duration of the conference has become a standard of the ISMB and ECCB conference series, and an extensive commercial exhibition showcases the latest bioinformatics publications, software, hardware and services available on the market today. The main conference is preceded by 2 days of Special Interest Group (SIG) and Satellite meetings running in parallel to the fifth Student Council Symposium on 27 June, and in parallel to Tutorials on 28 June. All scientific sessions take place at the Stockholmsmässan/Stockholm International Fairs conference and exposition facility.
PMCID: PMC2687994  PMID: 19447790
3.  The SPS100 gene of Saccharomyces cerevisiae is activated late in the sporulation process and contributes to spore wall maturation. 
Molecular and Cellular Biology  1988;8(2):912-922.
We previously described the use of a differential hybridization screen of a genomic DNA library of Saccharomyces cerevisiae to identify sporulation-specific (SPS) genes (A. Percival-Smith and J. Segall, Mol. Cell. Biol. 4:142-150, 1984). This initial screen identified 14 SPS genes that are first expressed 6 to 8 h after transfer of cells to sporulation medium. Accumulation of transcripts corresponding to these genes becomes maximal at 8 to 12 h of sporulation, the time at which meiotic events are nearing completion, and by 15 h of sporulation, transcript levels are beginning to decrease. In the present study two additional SPS genes, first expressed at 12 h of sporulation, were isolated. The steady-state level of transcripts corresponding to these two genes, termed SPS100 and SPS101, remains unchanged from 15 to 35 h, a time coincident with spore wall maturation. The nature of the putative 34.2-kilodalton protein encoded by the SPS100 gene is consistent with its being a component of the glycoprotein matrix of the spore wall; the protein contains a potential signal sequence and cleavage site and numerous sites for potential glycosylation. A MATa sps100/MAT alpha sps100 strain was found to be indistinguishable from the wild-type strain when assessed for efficiency of ascus formation and spore viability. However, a more detailed analysis of the mutant strain revealed that the SPS100 gene product serves a protective role during the early stages of spore wall formation. The time at which resistance to ether could first be detected in developing spores was delayed by 5 h in the mutant strain relative to the wild-type strain. This phenotype is presumably a reflection of a defect in spore wall maturation. This study has confirmed that temporally distinct classes of sporulation-specific genes are sequentially activated during the process of meiosis and spore formation and has shown that the SPS100 gene, identified on the basis of its developmental-specific expression pattern, contributes to spore development.
PMCID: PMC363223  PMID: 3280971
4.  InCoB celebrates its tenth anniversary as first joint conference with ISCB-Asia 
BMC Genomics  2011;12(Suppl 3):S1.
In 2009 the International Society for Computational Biology (ISCB) started to roll out regional bioinformatics conferences in Africa, Latin America and Asia. The open and competitive bid for the first meeting in Asia (ISCB-Asia) was awarded to Asia-Pacific Bioinformatics Network (APBioNet) which has been running the International Conference on Bioinformatics (InCoB) in the Asia-Pacific region since 2002. InCoB/ISCB-Asia 2011 is held from November 30 to December 2, 2011 in Kuala Lumpur, Malaysia. Of 104 manuscripts submitted to BMC Genomics and BMC Bioinformatics conference supplements, 49 (47.1%) were accepted. The strong showing of Asia among submissions (82.7%) and acceptances (81.6%) signals the success of this tenth InCoB anniversary meeting, and bodes well for the future of ISCB-Asia.
PMCID: PMC3333168  PMID: 22369160
5.  ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus 
PLoS Computational Biology  2015;11(1):e1004087.
Speed is of the essence in combating Ebola; thus, computational approaches should form a significant component of Ebola research. As for the development of any modern drug, computational biology is uniquely positioned to contribute through comparative analysis of the genome sequences of Ebola strains as well as 3-D protein modeling. Other computational approaches to Ebola may include large-scale docking studies of Ebola proteins with human proteins and with small-molecule libraries, computational modeling of the spread of the virus, computational mining of the Ebola literature, and creation of a curated Ebola database. Taken together, such computational efforts could significantly accelerate traditional scientific approaches. In recognition of the need for important and immediate solutions from the field of computational biology against Ebola, the International Society for Computational Biology (ISCB) announces a prize for an important computational advance in fighting the Ebola virus. ISCB will confer the ISCB Fight against Ebola Award, along with a prize of US$2,000, at its July 2016 annual meeting (ISCB Intelligent Systems for Molecular Biology [ISMB] 2016, Orlando, Florida).
PMCID: PMC4310586  PMID: 25633975
6.  Introduction of a Lysine Residue Promotes Aggregation of Temporin L in Lipopolysaccharides and Augmentation of Its Antiendotoxin Property 
Temporin L (TempL) is a 13-residue frog antimicrobial peptide that shows moderate bactericidal activity and antiendotoxin properties in macrophages. We envisioned that, due to its very hydrophobic nature, the peptide might fail to show its desired biological properties. It was predicted by employing the available algorithms that the replacement of a glutamine by lysine at position 3 could appreciably reduce its aggregation propensity in an aqueous environment. In order to investigate the structural, functional, and biological consequences of replacement of glutamine by lysine at its third position, TempL and the corresponding analog, Q3K-TempL, was synthesized and characterized. Introduction of the lysine residue significantly promoted the self-assembly and oligomeric state of TempL in lipopolysaccharide (LPS). Q3K-TempL exhibited augmented binding to LPS and also dissociated LPS aggregates with greater efficacy than TempL. Further, Q3K-TempL inhibited the LPS-induced proinflammatory cytokines in rat primary macrophages in vitro and in vivo in BALB/c mice with greater efficacy than TempL. The results showed that a simple amino acid substitution in a short hydrophobic antimicrobial peptide, TempL, enhanced its antiendotoxin properties and illustrate a plausible correlation between its aggregation properties in LPS and LPS detoxification activity.
PMCID: PMC3716152  PMID: 23478966
7.  Co-occurrence and distribution of East (L1014S) and West (L1014F) African knock-down resistance in Anopheles gambiae sensu lato population of Tanzania 
Insecticide resistance molecular markers can provide sensitive indicators of resistance development in Anopheles vector populations. Assaying these makers is of paramount importance in the resistance monitoring programme. We investigated the presence and distribution of knock-down resistance (kdr) mutations in Anopheles gambiae s.l. in Tanzania.
Indoor-resting Anopheles mosquitoes were collected from 10 sites and tested for insecticide resistance using the standard WHO protocol. Polymerase chain reaction-based molecular diagnostics were used to genotype mosquitoes and detect kdr mutations.
The An. gambiae tested were resistance to lambdacyhalothrin in Muheza, Arumeru and Muleba. Out of 350 An. gambiae s.l. genotyped, 35% were An. gambiae s.s. and 65% An. arabiensis. L1014S and L1014F mutations were detected in both An. gambiae s.s. and An. arabiensis. L1014S point mutation was found at the allelic frequency of 4–33%, while L1014F was at the allelic frequency 6–41%. The L1014S mutation was much associated with An. gambiae s.s. (χ2 = 23.41; P < 0.0001) and L1014F associated with An. arabiensis (χ2 = 11.21; P = 0.0008). The occurrence of the L1014S allele was significantly associated with lambdacyhalothrin resistance mosquitoes (Fisher exact P < 0.001).
The observed co-occurrence of L1014S and L1014F mutations coupled with reports of insecticide resistance in the country suggest that pyrethroid resistance is becoming a widespread phenomenon among our malaria vector populations. The presence of L1014F mutation in this East African mosquito population indicates the spreading of this gene across Africa. The potential operational implications of these findings on malaria control need further exploration.
Les marqueurs moléculaires de la résistance aux insecticides peuvent fournir des indicateurs sensibles du développement de la résistance dans les populations de vecteurs Anopheles. Le test de ces indicateurs est d'une importance énorme dans le programme de surveillance de la résistance. Nous avons étudié la présence et la répartition des mutations de résistance knockdown (kdr) chez Anopheles gambiae s.l. en Tanzanie.
Des anophèles d'intérieur, au repos ont été collectées dans 10 sites et testées pour la résistance aux insecticides en utilisant le protocole standard de l'OMS. Les diagnostics moléculaires basés sur la PCR ont été utilisés pour le génotypage des moustiques et la détection des génotypes kdr.
Les An. gambiae testées étaient résistantes à la lambdacyhalothrine à Muheza, Arumeru et Muleba. Sur 350 An. gambiae s.l. génotypées, 35% étaient An. gambiae s.s. et 65% étaient An. arabiensis. Les mutations L1014S et L1014F ont été détectées à la fois chez An. gambiae s.s. et An. arabiensis. La mutation ponctuelle L1014S a été trouvée à la fréquence allélique de 4 à 33%, tandis que L1014F était à la fréquence allélique de 6 à 14%. La mutation L1014S a été fortement associée à An. gambiae s.s. (Chi carré = 23,41; P<0,0001) et L1014F était associée à An. arabiensis (chi carré = 11,21; P = 0,0008). L'allèle L1014S était significativement associé aux moustiques résistants à la lambdacyhalothrine (Fisher P exact <0,001).
La cooccurrence des mutations L1014S et L1014F couplées à des rapports sur la résistance aux insecticides suggèrent que la résistance aux pyréthrinoïdes est en train de devenir un phénomène répandu dans les populations de vecteurs du paludisme en Tanzanie. La présence de la mutation L1014F dans cette population de moustiques en Afrique de l'Est indique la propagation de ce gène à travers l'Afrique. L'investigation des implications opérationnelles potentielles de ces résultats sur le contrôle du paludisme devraient être approfondie.
Los marcadores moleculares de resistencia a insecticidas pueden ser indicadores sensibles del desarrollo de resistencias en las poblaciones de los vectores Anopheles. Evaluar dichos marcadores es crucial para los programas de monitorización de resistencias. Hemos investigado la presencia y la distribución de las mutaciones de resistencia knockdown (kdr) en Anopheles gambiae s.l. en Tanzania.
Se recolectaron mosquitos Anopheles intradomiciliarios de 10 lugares diferentes y se evaluaron en busca de resistencia a insecticidas utilizando el protocolo estándar de la OMS. Mediante un diagnóstico molecular basado en la PCR se genotiparon los mosquitos y se detectaron los genotipos kdr.
Los An. gambiae evaluados eran resistentes a lambdacialotrina en Muheza, Arumeru y Muleba. De 350 An. gambiae s.l. genotipados, 35% eran An. gambiae s.s. y 65% eran An. arabiensis. Se detectaron mutaciones L1014S y L1014F tanto en An. gambiae s.s. como en An. arabiensis. La mutación puntual L1014S se encontró con una frecuencia alélica de 4-33%, mientras que L1014F tenía una frecuencia alélica de 6-14%. La mutación L1014S estaba ampliamente asociada a An. gambiae s.s. (Chi-Cuadrado = 23.41; P < 0.0001) y la L1014F estaba asociada con An. arabiensis (Chi-Square = 11.21; P = 0.0008). El alelo L1014S estaba significativamente asociado con mosquitos resistentes a la lambdacialotrina (P < 0.001).
La simultaneidad de mutaciones de L1014S y L1014F junto con informes de resistencia a los insecticidas sugiere que la resistencia a piretroides se está convirtiendo en un fenómeno común entre las poblaciones del vector de la malaria en Tanzania. La presencia de la mutación L1014F en estas poblaciones del Este de África indican la diseminación del gen a lo largo del continente africano. Determinar las implicaciones potenciales a nivel operativo de estos hallazgos sobre el control de la malaria requiere de más estudios.
PMCID: PMC4190685  PMID: 24386946
kdr; L1014S; L1014F; insecticide resistance; Anopheles gambiae; Tanzania
8.  Cognitive Components of Regularity Processing in the Auditory Domain 
PLoS ONE  2008;3(7):e2650.
Music-syntactic irregularities often co-occur with the processing of physical irregularities. In this study we constructed chord-sequences such that perceived differences in the cognitive processing between regular and irregular chords could not be due to the sensory processing of acoustic factors like pitch repetition or pitch commonality (the major component of ‘sensory dissonance’).
Methodology/Principal Findings
Two groups of subjects (musicians and nonmusicians) were investigated with electroencephalography (EEG). Irregular chords elicited an early right anterior negativity (ERAN) in the event-related brain potentials (ERPs). The ERAN had a latency of around 180 ms after the onset of the music-syntactically irregular chords, and had maximum amplitude values over right anterior electrode sites.
Because irregular chords were hardly detectable based on acoustical factors (such as pitch repetition and sensory dissonance), this ERAN effect reflects for the most part cognitive (not sensory) components of regularity-based, music-syntactic processing. Our study represents a methodological advance compared to previous ERP-studies investigating the neural processing of music-syntactically irregular chords.
PMCID: PMC2440538  PMID: 18612421
9.  Paving the future: finding suitable ISMB venues 
Bioinformatics  2012;28(19):2556-2559.
The International Society for Computational Biology, ISCB, organizes the largest event in the field of computational biology and bioinformatics, namely the annual international conference on Intelligent Systems for Molecular Biology, the ISMB. This year at ISMB 2012 in Long Beach, ISCB celebrated the 20th anniversary of its flagship meeting. ISCB is a young, lean and efficient society that aspires to make a significant impact with only limited resources. Many constraints make the choice of venues for ISMB a tough challenge. Here, we describe those challenges and invite the contribution of ideas for solutions.
PMCID: PMC3463122  PMID: 22796959
10.  Role of a Disordered Steroid Metabolome in the Elucidation of Sterol and Steroid Biosynthesis 
Lipids  2011;47(1):1-12.
In 1937 Butler and Marrian found large amounts of the steroid pregnanetriol in urine from a patient with the adrenogenital syndrome, a virilizing condition known to be caused by compromised adrenal secretion even in this pre-cortisol era. This introduced the concept of the study of altered excretion of metabolites as an in vivo tool for understanding sterol and steroid biosynthesis. This approach is still viable and has experienced renewed significance as the field of metabolomics. From the first cyclized sterol lanosterol to the most downstream product estradiol, there are probably greater than 30 steps. Based on a distinctive metabolome clinical disorders have now been attributed to about seven post-squalene cholesterol (C) biosynthetic steps and around 15 en-route to steroid hormones or needed for further metabolism of such hormones. Forty years ago it was widely perceived that the principal steroid biosynthetic defects were known but interest rekindled as novel metabolomes were documented. In his career this investigator has been involved in the study of many steroid disorders, the two most recent being P450 oxidoreductase deficiency and apparent cortisone reductase deficiency. These are of interest as they are due not to mutations in the primary catalytic enzymes of steroidogenesis but in ancillary enzymes needed for co-factor oxido-reduction A third focus of this researcher is Smith-Lemli-Opitz syndrome (SLOS), a cholesterol synthesis disorder caused by 7-dehydrocholesterol reductase mutations. The late George Schroepfer, in whose honor this article has been written, contributed greatly to defining the sterol metabolome of this condition. Defining the cause of clinically severe disorders can lead to improved treatment options. We are now involved in murine gene therapy studies for SLOS which, if successful could in the future offer an alternative therapy for this severe condition.
PMCID: PMC3564490  PMID: 21874273
Cholesterol synthesis; Steroid biosynthesis; Steroid metabolism
11.  Influence of headache frequency on clinical signs and symptoms of TMD in subjects with temple headache and TMD pain 
Pain  2010;152(4):765-771.
The relationship of the frequency of temple headache to signs and symptoms of temporomandibular disorders (TMD) was investigated in a subset of a larger convenience sample of community TMD cases. The study sample included: 86 painful TMD, non-headache subjects; 309 painful TMD subjects with varied frequency of temple headaches; and 149 subjects without painful TMD or headache for descriptive comparison. Painful TMD included Research Diagnostic Criteria (RDC) diagnoses of myofascial pain, TMJ arthralgia and TMJ osteoarthritis. Mild to moderate intensity temple headaches were classified by frequency using criteria based on the ICHD-II classification of TTH. Outcomes included TMD signs and symptoms (pain duration, pain intensity, number of painful masticatory sites on palpation, mandibular range of motion), PPTs and temple headache resulting from masticatory provocation tests. Trend analyses across the painful TMD groups showed a substantial trend for aggravation of all of the TMD signs and symptoms associated with increased frequency of the temple headaches. In addition, increased headache frequency showed significant trends associated with reduced PPTs and reported temple headache with masticatory provocation tests. In conclusion, these findings suggest that these headaches may be TMD-related, as well as a possible role for peripheral and central sensitization in TMD patients.
PMCID: PMC3065515  PMID: 21196079
temporomandibular disorders; headache; signs; symptoms; myofascial pain; TMD pain
12.  Predictors of Change in Bodily Pain in Early Rheumatoid Arthritis: An Inception Cohort Study 
Arthritis Care & Research  2012;64(10):1505-1513.
To investigate possible predictors for lack of pain improvement after 1 year of treatment for early rheumatoid arthritis (RA).
The Early Rheumatoid Arthritis Network (ERAN) database was used for analysis of baseline and 1-year pain data. The ERAN is a hospital-based inception cohort of 1,189 people. Short Form 36 questionnaire bodily pain scores were used to calculate change in pain at 1 year as the outcome. The proportion of the Disease Activity Score in 28 joints (DAS28) attributable to patient-reported components (joint tenderness and visual analog scale score; DAS28-P) at baseline was derived as a predictor. Predictors of less improvement in pain were investigated using adjusted odds ratios (ORadj) generated by logistic regression, adjusting for 14 additional clinical and demographic covariates.
Greater pain at baseline was associated with sex, high DAS28, worse mental health, and smoking. Most patients with early RA reported incomplete improvement in bodily pain after 1 year. The DAS28-P index did not significantly change in the patients whose disease remained active. Less improvement in pain was predicted by female sex (ORadj 3.41, 95% confidence interval [95% CI] 1.35–8.64) and a high DAS28-P index at baseline (ORadj for tertiles 2.09, 95% CI 1.24–3.55). Other conventional RA risk factors did not predict pain changes.
The factors most likely to predict less improvement in pain in early RA are female sex and a high DAS28-P index. A high DAS28-P index may reflect greater contributions of noninflammatory factors, such as central sensitization, to pain. Strategies in addition to inflammatory disease suppression may be required to adequately treat pain.
PMCID: PMC3770924  PMID: 22556121
13.  Effects of Unexpected Chords and of Performer's Expression on Brain Responses and Electrodermal Activity 
PLoS ONE  2008;3(7):e2631.
There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown.
Methodology/Principal Findings
This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition.
These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.
PMCID: PMC2435625  PMID: 18612459
14.  Towards big data science in the decade ahead from ten years of InCoB and the 1st ISCB-Asia Joint Conference 
BMC Bioinformatics  2011;12(Suppl 13):S1.
The 2011 International Conference on Bioinformatics (InCoB) conference, which is the annual scientific conference of the Asia-Pacific Bioinformatics Network (APBioNet), is hosted by Kuala Lumpur, Malaysia, is co-organized with the first ISCB-Asia conference of the International Society for Computational Biology (ISCB). InCoB and the sequencing of the human genome are both celebrating their tenth anniversaries and InCoB’s goalposts for the next decade, implementing standards in bioinformatics and globally distributed computational networks, will be discussed and adopted at this conference. Of the 49 manuscripts (selected from 104 submissions) accepted to BMC Genomics and BMC Bioinformatics conference supplements, 24 are featured in this issue, covering software tools, genome/proteome analysis, systems biology (networks, pathways, bioimaging) and drug discovery and design.
PMCID: PMC3278825  PMID: 22372736
15.  Summary of talks and papers at ISCB-Asia/SCCG 2012 
BMC Genomics  2013;14(Suppl 2):I1.
The second ISCB-Asia conference of the International Society for Computational Biology took place December 17-19, 2012, in Shenzhen, China. The conference was co-hosted by BGI as the first Shenzhen Conference on Computational Genomics (SCCG).
45 talks were presented at ISCB-Asia/SCCG 2012. The topics covered included software tools, reproducible computing, next-generation sequencing data analysis, transcription and mRNA regulation, protein structure and function, cancer genomics and personalized medicine. Nine of the proceedings track talks are included as full papers in this supplement.
In this report we first give a short overview of the conference by listing some statistics and visualizing the talk abstracts as word clouds. Then we group the talks by topic and briefly summarize each one, providing references to related publications whenever possible. Finally, we close with a few comments on the success of this conference.
PMCID: PMC3639071
16.  Soft Skills: An Important Asset Acquired from Organizing Regional Student Group Activities 
PLoS Computational Biology  2014;10(7):e1003708.
Contributing to a student organization, such as the International Society for Computational Biology Student Council (ISCB-SC) and its Regional Student Group (RSG) program, takes time and energy. Both are scarce commodities, especially when you are trying to find your place in the world of computational biology as a graduate student. It comes as no surprise that organizing ISCB-SC-related activities sometimes interferes with day-to-day research and shakes up your priority list. However, we unanimously agree that the rewards, both in the short as well as the long term, make the time spent on these extracurricular activities more than worth it. In this article, we will explain what makes this so worthwhile: soft skills.
PMCID: PMC4080995  PMID: 24992198
17.  Comparing Body Composition Assessment Tests in Long-term Hemodialysis Patients 
Protein-energy wasting is common in chronic kidney disease and is associated with reductions in body muscle and fat stores and poor outcomes. The accuracy and reliability of field methods to measure body composition is unknown in this population.
Study Design
Cross sectional, observational study.
Setting and Participants
118 maintenance hemodialysis patients were seen at the General Clinical Research Center at Harbor-UCLA Medical Center.
Index Tests
Triceps skinfold, near-infrared interactance, and bioelectrical impedance analysis using the Segal, Kushner and Lukaski equations
Reference Test
Dual energy X-ray absorptiometry (DEXA)
Participants (42% women, 52% diabetics, 40% African-Americans and 38% Hispanics were 49.4±11.5 (mean±SD) years old, and had undergone dialysis for 41.1±32.9 months. Their body mass index was 27.0±6.0 kg/m2. Using DEXA as the reference test, the bioelectrical impedance analysis–Kushner equation, and triceps skinfold and near-infrared interactance were most accurate of the index tests in estimating total body fat percentage, whereas bioelectrical impedance analysis–Segal equation and bioelectrical impedance analysis–Lukaski equation overestimated total body fat percentage. Bland-Altman analyses and Difference plots showed that bioelectrical impedance analysis–Kushner and near-infrared interactance were most similar to the reference test. Bioelectrical impedance analysis–Kushner, triceps skinfold and near-infrared interactance had the smallest mean differences from DEXA, especially in women (1.6%, 0.7% and 1.2%, respectively). Similar results were observed in African-American participants (n=47).
Measurements were performed one day after hemodialysis treatment leading to more fluid retention, which may have affected reference and index tests differently.
Using DEXA as the reference test, both near-infrared interactance and bioelectrical impedance analysis-Kushner method yield more consistent estimates of total body fat percentage in maintenance hemodialysis patients compared to the other index tests. The near-infrared interactance is not affected by skin color. Field methods with portable devices may provide adequate precision.
PMCID: PMC3175362  PMID: 20346558
Chronic kidney disease (CKD); hemodialysis; protein-energy wasting (PEW); near-infrared; bioelectrical impedance analysis (BIA); malnutrition
The purpose of this study was to review institutional statistics provided in dean's letters and determine the percentage of honors awarded by institution and clerkship specialty.
Institutional and clerkship aggregate data were compiled from a review of dean's letters from 80 United States medical schools. The percentage of honors awarded during 3rd year clerkships during 2005 were collected for analysis. Across clerkship specialties, there were no statistically significant differences between the mean percentage of honors given by the medical schools examined with Internal Medicine (27.6%) the low and Psychiatry (33.5%) the high. However, inter-institutional variability observed within each clerkship was high, with surgery clerkship percentage of honors ranging from 2% to 75% of the students. This suggests some schools may be more lenient and other more stringent in awarding honors to their students. This inter-institutional variability makes it difficult to compare honors received by students from different medical schools and weakens the receipt of honors as a primary tool for evaluating potential incoming residents.
PMCID: PMC2723699  PMID: 19742092
19.  Land Donations and the Gift of Water. On Temple Landlordism and Irrigation Agriculture in Pre-Colonial Bali 
Human Ecology  2011;39(1):43-53.
The Batur Temple (Pura Ulun Danu Batur) in Kintamani is located at the geographic apex of a so-called ritual water hierarchy and has conventionally been described as a purely religious institution responsible for the coordination and distribution of the irrigation water. However, an analysis of historical palm leaf manuscripts reveals that the temple had a firm economic base with corresponding interests and that it was one of the most important land-owners in late pre-colonial Bali. The article therefore explores from a socio-political and economic perspective the implications of this form of temple landlordism and its combination with ritual water control, particularly for the peasants and the portion of their annual surplus that they were obliged to deliver to this temple.
PMCID: PMC3056004  PMID: 21475724
Bali; Water management; Subak; Wet-rice production; Landlordism; Temple
20.  Breast augmentation: A geographical comparison 
To describe and compare physical characteristics and implant details of women undergoing primary cosmetic breast augmentation in different geographical locations.
Three cohorts of 100 consecutive breast augmentation cases in university settings were retrospectively reviewed for patient demographic and implant information in Kelowna (British Columbia), Loma Linda (California, USA) and Temple (Texas, USA). Statistical analysis was performed with a Kruskal-Wallis test without normality assumption (P<0.05 was considered to be significant). Pearson correlation coefficients were also determined for body mass index (BMI) versus implant volume at each of the sites.
The three group medians were significantly different for weight, BMI and implant volume. Kelowna’s average patient was 33 years of age, had a BMI of 20.8 kg/m2 and an implant volume of 389 mL. Loma Linda’s average patient was 32 years of age, had a BMI of 21.6 kg/m2 and an implant volume of 385 mL. Temple’s average patient was 36 years of age, had a BMI of 22.6 kg/m2 and an implant volume of 335 mL. Pearson correlations for BMI versus implant volume were statistically significant in the Loma Linda and Temple groups.
Patients from different geographical locations undergoing breast augmentation were similar in age, height and parity, but varied in weight, BMI and implant volume. A positive linear correlation between BMI and implant volume was found in the American cohorts.
PMCID: PMC3006117  PMID: 22131846
Body mass index; Breast augment; Implant volume
Ancient Science of Life  1997;17(2):94-99.
This paper is a brief survey of the role of temples and holy places in nurturing the surrounding flora and its habitat. Eightysix kinds of plants in temple yards and gardens of orissa have been enlisted where they are cultivated and preserved for different temple rituals. These plants are seen rarely in wild but are saved from extinction by their association with temple rituals and ceremonies.
PMCID: PMC3331100  PMID: 22556826
22.  A Simple Intervention to Prevent Cutaneous Larva Migrans among Devotees of the Nallur Temple in Jaffna, Sri Lanka 
PLoS ONE  2013;8(4):e61816.
A cross sectional study conducted during the annual festival at Nallur temple in Jaffna, Sri Lanka, in 2010, showed that the prevalence of cutaneous larva migrants (CLM) among the devotees who performed the side roll ritual was 58.2% (95%CI: 51.2%–65.0%).
To test the hypothesis that the deworming stray dogs around the temple premises effectively reduces the prevalence of CLM among devotees.
Methodology/Principal Findings
All stray dogs (8) in the vicinity of the temple were treated, with mebendazole (100 mg) crushed and filled into sausages, 10 days before the commencement of festival in 2011. The same procedure was repeated a week later to ensure complete coverage. A cross-sectional study was conducted among 200 systematically selected devotees in August 2011 using an interviewer-administered questionnaire and the clinical examination of the skin. Baermann's technique was used for the recovery of nematode larvae from 40 soil samples collected from the temple premises. Ten samples of dog faeces collected from the same premises were also examined for nematode eggs. Prevalence of CLM among devotees in 2010 (Pre intervention) and 2011(Post intervention) were compared to test the hypothesis. Prevalence of CLM declined from 58% to 8% (Chi-square = 112.90, p<0.001) following the intervention. None of the subjects practiced new precautionary measures compared to the previous year. Soil and fecal samples were negative for parasites.
Regular dog deworming is an important and effective method for the prevention of CLM among the devotees doing side roll ritual and represents a pragmatic intervention that municipal authorities could perform on annual basis.
PMCID: PMC3629127  PMID: 23613943
23.  Multidisciplinary management of hepatocellular carcinoma: a model for therapy 
A multidisciplinary model is a useful approach in the management of hepatocellular carcinoma (HCC) to coordinate, individualize, and optimize care. The HCC Multidisciplinary Team (MDT) at Temple University Hospital was established in 2008 and comprises hepatologists, interventional radiologists, transplant surgeons, oncologists, residents, midlevel providers, and support staff. Patients may be enrolled by referral from (1) oncologists at Temple, (2) the hepatitis screening clinic recently established at Temple and staffed by hepatology residents, or (3) community practices. MDT conferences are held weekly, during which cases are discussed (based on medical history, interpretation of images, and laboratory analyses) and treatment plans are formulated. The Temple treatment algorithm follows current standards of care, guided by tumor volume and morphology, but the novel multidisciplinary interaction challenges members to tailor therapy to achieve the best possible outcomes. Patients with a solitary lesion ≤ 2 cm may receive no treatment until eligible for transplantation or locoregional therapy or resection, with imaging every 3 to 6 months to monitor tumor progression. In patients with tumors > 2 cm and ≤ 5 cm, microwave ablation therapy is used if lesions are discrete and accessible. Conventional transarterial chemoembolization (TACE) or drug-eluting bead TACE (DEB-TACE) or yttrium-90 microspheres are utilized in multifocal disease. Patients with lesions > 5 cm are candidates for TACE for downstaging the tumor. Sorafenib is typically reserved for unresectable lesions between 2 cm and 5 cm. Frequently, we administer sorafenib continuously and in combination with DEB-TACE. In our experience, sorafenib does not produce effects on the tumor vasculature or blood flow that would impair the efficacy of DEB-TACE. The literature documents improved outcomes in HCC and other cancers associated with the introduction of multidisciplinary care. The role and organization of the MDT is influenced by team culture, expertise, and process, as well as institutional and larger environmental contexts.
PMCID: PMC3656893  PMID: 23690690
HCC; coordinated care; interdisciplinary; transplant
24.  Could shame and honor save cooperation? 
Shame and honor are mechanisms that expose behavior that falls outside the social norm. With recent six-player public goods experiments, we demonstrated that the threat of shame or the promise of honor led to increased cooperation. Participants were told in advance that after ten rounds two participants would be asked to come forward and write their names on the board in front of the fellow group members. In the shame treatment, the least cooperative players were exposed and wrote their names under the sentence “I donated least” while the honored participants wrote their name under “I donated most.” In both the shame and honor treatments, participants contributed approximately 50% more to the public good, as compared with the control treatment in which all players retained their anonymity. Here, we also discuss how shame and honor differ from full transparency, and some of the challenges to understanding how anonymity and exposure modify behavior.
PMCID: PMC3376067  PMID: 22808336
cooperation; honor; public goods game; shame; tragedy of the commons
25.  Psychometric properties of the modified Symptom Severity Index (SSI) 
Journal of oral rehabilitation  2009;37(1):11-20.
The psychometric properties of the modified Symptom Severity Index were investigated to assess the relationships among dimensions of pain in temporomandibular disorders. The 15-item instrument is composed of ordinal scales assessing five pain dimensions (intensity, frequency, duration, unpleasantness, and difficulty to endure) as experienced in three locations (temple, temporomandibular joint, masseter). In 108 closed-lock subjects, Cronbach’s alpha was used to measure internal consistency resulting in 31 of the 105 pair-wise comparisons ≥0.71. Multilevel exploratory factor analysis was used to assess dimensionality between items. Two factors emerged, termed temple pain and jaw pain. The jaw pain factor comprised the temporomandibular joint and masseter locations, indicating that subjects did not differentiate between these two locations. With further analysis, the jaw pain factor could be separated into temporal aspects of pain (frequency, duration) and affective dimensions (intensity, unpleasantness, endurability). Temple pain could not be further reduced; this may have been influenced by concurrent orofacial pains such as headache. Internal consistency was high, with alphas ≥0.92 for scales associated with all factors. Excellent test-retest reliability was found for repeat testing at 2–48 hours in 55 subjects (ICC=0.97, 95%CI 0.96–0.99). In conclusion, the modified Symptom Severity Index has excellent psychometric properties for use as an instrument to measure pain in subjects with temporomandibular disorders. The most important characteristic of this pain is location, while the temporal dimensions are important for jaw pain. Further research is needed to confirm these findings and assess relationships between dimensions of pain as experienced in other chronic pain disorders.
PMCID: PMC2858780  PMID: 19889036
Pain dimensions; pain assessment; reliability; factor analysis; temporomandibular disorders (TMD); orofacial pain

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