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In forensic, medical and veterinary entomology, the ease and affordability of image data acquisition have resulted in whole-image analysis becoming an invaluable approach for species identification. Krawtchouk moment invariants are a classical mathematical transformation that can extract local features from an image, thus allowing subtle species-specific biological variations to be accentuated for subsequent analyses. We extracted Krawtchouk moment invariant features from binarised wing images of 759 male fly specimens from the Calliphoridae, Sarcophagidae, and Muscidae families (13 species and a species variant). Subsequently, we trained the Generalized, Unbiased, Interaction Detection and Estimation (GUIDE) random forests classifier using linear discriminants derived from these features and inferred the species identity of specimens from the test samples. Five-fold cross validation results show a 98.56 ± 0.38% (standard error) identification accuracy at the family level, and a 91.04 ± 1.33% identification accuracy at the species level. The mean F1-score of 0.89 ± 0.02 reflects good balance of precision and recall properties of the model. The present study consolidates findings from previous small pilot studies of the usefulness of wing venation patterns for inferring species identities. Thus, the stage is set for the development of a mature data analytic ecosystem for routine computer image-based identification of fly species that are of forensic, medical, and veterinary importance.

SummaryGenes that show differential variability between conditions are important for complementing a systems biology understanding of the molecular players involved in a biological process. Under the dominant paradigm for modeling RNA-Seq gene counts using the negative binomial model, tests of differential variability are challenging to develop, owing to dependence of the variance on the mean. The limited availability of methods for detecting genes with differential variability means that researchers often omit differential variability as an analytical step in RNA-Seq data analysis. Here, we describe clrDV, a statistical method for detecting genes that show differential variability between two populations. clrDV is based on a compositional data analysis framework. We present the skew-normal distribution for modeling gene-wise null distribution of centered log-ratio transformation of compositional RNA-seq data. Simulation results show that clrDV has false discovery rate and Type II error that are on par with or superior to existing methodologies. In addition, its run time is faster than the closest competitor’s, and remains relatively constant for increasing sample size per group. Analysis of a large neurodegenerative disease RNA-Seq dataset using clrDV recovers multiple gene candidates that have been reported to be associated with Alzheimer’s disease. Additionally, we find that the majority of genes with differential variability have smaller relative gene expression variance in the Alzheimer’s disease population compared to the control population.

To evaluate ocular surface changes among patients with psoriasis in Malaysia, a developing country in Southeast Asia. An interdisciplinary case–control study (60 psoriasis patients and 40 control subjects) to look at the differences in ocular surface manifestations between patients with psoriasis and a group of age-, gender- and ethnicity-matched healthy controls. One hundred and twenty eyes of 60 patients with psoriasis and 80 eyes of 40 healthy controls without psoriasis were included in the study. Mild-to-moderate psoriasis was found in 42 patients (70%), while 18 patients (30%) had severe psoriasis. Psoriatic arthritis was found in 19 patients (32%). Of the 60 psoriatic patients, the prevalence of ocular involvement was 65% (39/60), in which 32% (19/60) had dry eyes, 27% (16/60) had lid margin abnormalities, 33% (20/60) had cataract, and one had history of anterior uveitis. Compared to controls, ocular surface of psoriatic patients showed more eyelid margin abnormalities, higher meibomian gland loss and lower tear film break-up time. The estimated odds ratio for dry eyes in the psoriasis group was 2.2 (95% CI: 0.8–6.9). Ocular surface disorders encompassing eyelid margin abnormalities, meibomian gland loss and tear dysfunction occur at an earlier and higher rate among psoriatic patients.

Aim Freshwater planarians may have a wide geographical range despite their assumed low vagility. Found across four continents, Dugesia may have either an ancient origin on a large palaeo landmass, followed by colonisation in different regions before continental fragmentation, or a more recent origin and subsequent transoceanic dispersal. We seek to resolve between these two hypotheses. Location Africa, Eurasia and Australasia. Taxon Genus Dugesia (Platyhelminthes: Tricladida: Dugesiidae). Methods We used data from the sequencing of six gene fragments and comprehensive taxonomic sampling of Dugesia from across its distribution range to reconstruct the phylogeny of this genus using maximum likelihood and bayesian inference methods. We conducted two phylogenetic dating analyses using Platyhelminthes fossils and palaeogeological events. Basing on the time-calibrated molecular phylogenetic framework we evaluated the contribution of vicariance and dispersal to the biogeographical evolution of Dugesia. By reconstructing the ancestral areas and present-day potential distribution using BioGeoBEARS and niche modelling, we elucidated the biogeographical history of the genus. Results The present-day distribution of Dugesia is a result of different vicariance and dispersal events. However, we also found evidence of transoceanic dispersal. Consistent with previous hypotheses, Dugesia dates to the Upper Jurassic in the Afro-Malagasy Gondwana region. We unveiled a novel biogeographical scenario for the genus, involving multiple events of colonisation in Eurasia from continental Africa via at least three dispersal routes. Main conclusions Dugesia is an ancient genus having reached its present distribution through a complex history of dispersal and vicariant events following its origin in southern Gondwana. Despite the low vagility of Dugesia, we found evidence of their overseas dispersal.

We were asked by Innovation Embassy to work with a large dataset centred around gambling investment, with the task of making a predictive function for computing Customer Lifetime Value (CLV), and also to see if there are ways of detecting fraudulent financial practices and addictive gambling patterns. We had moderate success with the data as it stands, but we were partly held back for two main reasons: the ability to discern a solid definition of CLV due to highly inconsistent data and data that contained many large and incomputable gaps. Different machine learning algorithms were used to find CLV functions based on key variables. We also describe a short and explicit list of ways where the base data can be improved to support effective calculation of CLV. Our key findings suggest that the average customer's CLV is 1035 and ~80% of revenue is brought in from ~10% of the clients.

Wing shape variation has been shown to be useful for delineating forensically important fly species in two Diptera families: Calliphoridae and Sarcophagidae. Compared to DNA-based identification, the cost of geometric morphometric data acquisition and analysis is relatively much lower because the tools required are basic, and stable softwares are available. However, to date, an explicit demonstration of using wing geometric morphometric data for species identity prediction in these two families remains lacking. Here, geometric morphometric data from 19 homologous landmarks on the left wing of males from seven species of Calliphoridae (n = 55), and eight species of Sarcophagidae (n = 40) were obtained and processed using Generalized Procrustes Analysis. Allometric effect was removed by regressing centroid size (in log10 ) against the Procrustes coordinates. Subsequently, principal component analysis of the allometry-adjusted Procrustes variables was done, with the first 15 principal components used to train a random forests model for species prediction. Using a real test sample consisting of 33 male fly specimens collected around a human corpse at a crime scene, the estimated percentage of concordance between species identities predicted using the random forests model and those inferred using DNA-based identification was about 80.6% (approximate 95% confidence interval = [68.9%, 92.2%]). In contrast, baseline concordance using naive majority class prediction was 36.4%. The results provide proof of concept that geometric morphometric data has good potential to complement morphological and DNA-based identification of blow flies and flesh flies in forensic work.

It is now increasingly common for breast cancer patients to receive adjuvant tamoxifen therapy for a period of up to 10 years. As survival rate increases, managing tamoxifen ocular toxicities is important for patients' quality of life. Macular pigments in photoreceptor cells protect against free radical damage, which can cause macular degeneration. By reducing macular pigment concentration, tamoxifen may increase the risk of macular degeneration. Here, we compared macular pigment optical density (MPOD) and central macular thickness between breast cancer patients on tamoxifen adjuvant therapy (n = 70), and a control group (n = 72). Multiple regression analysis indicated that MPOD decreases with increasing tamoxifen dosage, up to a threshold of about 20 g, after which MPOD plateaus out. Mean MPOD in the treatment group (mean = 0.40) was significantly lower (p-value = 0.02) compared to the control group (mean = 0.47) for the left eye, and for the right eye (treatment mean = 0.39; control mean = 0.48; p-value = 0.009). No significant difference in mean central macular thickness was found between the treatment and the control group (p-values 0.4). In the control group, MPOD and central macular thickness showed significant correlation (r∼0.30; p-values 0.01) for both eyes. However, in the treatment group, loss of significant correlation was observed in the left eye (r = 0.21; p-value = 0.08). The present results show that MPOD decreases non-linearly as a function of tamoxifen dosage, and highlight the potential of tamoxifen to reduce macular pigment concentration through an unknown mechanism that does not depend on macular thinning solely.

Objective With an age-standardized incidence rate of 2 per 100 000, esophageal cancer is not common among Malaysians, but they are nevertheless important due to its poor prognosis. The study is to clarify whether the human papillomavirus (HPV) is associated with esophageal cancer in Malaysians as there has been no report to date on this in Malaysians and other South East Asians. Methods Altogether 67 esophageal squamous cell carcinomas histologically diagnosed between 1 January 2004 and 31 December 2014 at the Department of Pathology, University of Malaya Medical Center, Malaysia were considered for HPV analysis using two commercially available methods, polymerase chain reaction with flow-through hybridization (21 HPV GenoArray Diagnostic Kit) and multiplex real-time polymerase chain reaction (Anyplex II HPV28 Detection). The DNA amplifiability of the formalin-fixed, paraffin-embedded tumor was checked by amplification of a 268 bp segment of the human β-globin gene (GH20/PC04) prior to HPV detection. Results HPV detection was finally carried out in 51 patients. HPV16 was detected in the moderately differentiated, stage IV lower esophageal tumor of a 32-year-old Malaysian-born Chinese woman by both methods. Except for a predilection for Indians, the clinical characteristics of esophageal squamous cell carcinomas in this Malaysian cohort were generally similar to those of other populations. Conclusion It appears that HPV is rare and an unlikely oncovirus in esophageal squamous cell carcinomas of Malaysians.

Head and neck cancer (HNC)–derived cell lines represent fundamental models for studying the biological mechanisms underlying cancer development and precision therapies. However, mining the genomic information of HNC cells from available databases requires knowledge on bioinformatics and computational skill sets. Here, we developed a user-friendly web resource for exploring, visualizing, and analyzing genomics information of commonly used HNC cell lines. We populated the current version of GENIPAC with 44 HNC cell lines from 3 studies: ORL Series, OPC-22, and H Series. Specifically, the mRNA expressions for all the 3 studies were derived with RNA-seq. The copy number alterations analysis of ORL Series was performed on the Genome Wide Human Cytoscan HD array, while copy number alterations for OPC-22 were derived from whole exome sequencing. Mutations from ORL Series and H Series were derived from RNA-seq information, while OPC-22 was based on whole exome sequencing. All genomic information was preprocessed with customized scripts and underwent data validation and correction through data set validator tools provided by cBioPortal. The clinical and genomic information of 44 HNC cell lines are easily assessable in GENIPAC. The functional utility of GENIPAC was demonstrated with some of the genomic alterations that are commonly reported in HNC, such as TP53, EGFR, CCND1, and PIK3CA. We showed that these genomic alterations as reported in The Cancer Genome Atlas database were recapitulated in the HNC cell lines in GENIPAC. Importantly, genomic alterations within pathways could be simultaneously visualized. We developed GENIPAC to create access to genomic information on HNC cell lines. This cancer omics initiative will help the research community to accelerate better understanding of HNC and the development of new precision therapeutic options for HNC treatment. GENIPAC is freely available at http://genipac.cancerresearch.my/ .

In image analysis, orthogonal moments are useful mathematical transformations for creating new features from digital images. Moreover, orthogonal moment invariants produce image features that are resistant to translation, rotation, and scaling operations. Here, we show the result of a case study in biological image analysis to help researchers judge the potential efficacy of image features derived from orthogonal moments in a machine learning context. In taxonomic classification of forensically important flies from the Sarcophagidae and the Calliphoridae family (n = 74), we found the GUIDE random forests model was able to completely classify samples from 15 different species correctly based on Krawtchouk moment invariant features generated from fly wing images, with zero out-of-bag error probability. For the more challenging problem of classifying breast masses based solely on digital mammograms from the CBIS-DDSM database (n = 1,151), we found that image features generated from the Generalized pseudo-Zernike moments and the Krawtchouk moments only enabled the GUIDE kernel model to achieve modest classification performance. However, using the predicted probability of malignancy from GUIDE as a feature together with five expert features resulted in a reasonably good model that has mean sensitivity of 85%, mean specificity of 61%, and mean accuracy of 70%. We conclude that orthogonal moments have high potential as informative image features in taxonomic classification problems where the patterns of biological variations are not overly complex. For more complicated and heterogeneous patterns of biological variations such as those present in medical images, relying on orthogonal moments alone to reach strong classification performance is unrealistic, but integrating prediction result using them with carefully selected expert features may still produce reasonably good prediction models.

We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell 500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We found Fusobacterium was significantly enriched among the HIV-infected and the sIR group. CCA results showed that Fusobacterium abundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higher Fusobacterium relative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment of Fusobacterium was associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.

With an age-standardized incidence rate of 2 per 100 000, esophageal cancer is not common among Malaysians, but they are nevertheless important due to its poor prognosis. The study is to clarify whether the human papillomavirus (HPV) is associated with esophageal cancer in Malaysians as there has been no report to date on this in Malaysians and other South East Asians.Altogether 67 esophageal squamous cell carcinomas histologically diagnosed between 1 January 2004 and 31 December 2014 at the Department of Pathology, University of Malaya Medical Center, Malaysia were considered for HPV analysis using two commercially available methods, polymerase chain reaction with flow-through hybridization (21 HPV GenoArray Diagnostic Kit) and multiplex real-time polymerase chain reaction (Anyplex II HPV28 Detection). The DNA amplifiability of the formalin-fixed, paraffin-embedded tumor was checked by amplification of a 268 bp segment of the human β-globin gene (GH20/PC04) prior to HPV detection.HPV detection was finally carried out in 51 patients. HPV16 was detected in the moderately differentiated, stage IV lower esophageal tumor of a 32-year-old Malaysian-born Chinese woman by both methods. Except for a predilection for Indians, the clinical characteristics of esophageal squamous cell carcinomas in this Malaysian cohort were generally similar to those of other populations.It appears that HPV is rare and an unlikely oncovirus in esophageal squamous cell carcinomas of Malaysians.

We hypothesise that the body shapes of three mudskipper species (Boleophthalmus dussumieri, Periophthalmus waltoni, and Scartelaos tenuis) are ecomorphological adaptations to different epi- and infaunal habitats. We investigated: (i) the association between burrow density and selected ecological variables; (ii) the phylogenetic relationships among these species, based on two mtDNA and one nDNA markers; (iii) their geometric morphometrics and ancestral shape reconstructions, based on two-dimensional landmark configurations; and (iv) their body surface-to-volume ratios (SAV), based on a geometric model. Boleophthalmus dussumieri and S. tenuis are more closely related, and more elongated than P. waltoni; the body of S. tenuis also has a higher SAV, and its elongated shape appears to be a divergent trait. P. waltoni is found in a wide range of conditions, including vegetated habitats; B. dussumieri is associated with low-energy conditions and fine unvegetated deposits; and S. tenuis is associated with high-energy conditions and coarser, non-cohesive sediments. These results suggest that body elongation in Scartelaos species is a divergent locomotory adaptation to marine habitats characterised by semi-liquid and less cohesive sediments. The more compact body shape of Periophthalmus species is hypothesised to have evolved from a gobionelline ancestor, and is proposed to be a preadaptation to subaerial locomotion in semi-terrestrial habitats.

Background The drug discovery and development pipeline is a long and arduous process that inevitably hampers rapid drug development. Therefore, strategies to improve the efficiency of drug development are urgently needed to enable effective drugs to enter the clinic. Precision medicine has demonstrated that genetic features of cancer cells can be used for predicting drug response, and emerging evidence suggest that gene-drug connections could be predicted more accurately by exploring the cumulative effects of many genes simultaneously. Results We developed DeSigN, a web-based tool for predicting drug efficacy against cancer cell lines using gene expression patterns. The algorithm correlates phenotype-specific gene signatures derived from differentially expressed genes with pre-defined gene expression profiles associated with drug response data (IC50) from 140 drugs. DeSigN successfully predicted the right drug sensitivity outcome in four published GEO studies. Additionally, it predicted bosutinib, a Src/Abl kinase inhibitor, as a sensitive inhibitor for oral squamous cell carcinoma (OSCC) cell lines. In vitro validation of bosutinib in OSCC cell lines demonstrated that indeed, these cell lines were sensitive to bosutinib with IC50 of 0.8–1.2 μM. As further confirmation, we demonstrated experimentally that bosutinib has anti-proliferative activity in OSCC cell lines, demonstrating that DeSigN was able to robustly predict drug that could be beneficial for tumour control. Conclusions DeSigN is a robust method that is useful for the identification of candidate drugs using an input gene signature obtained from gene expression analysis. This user-friendly platform could be used to identify drugs with unanticipated efficacy against cancer cell lines of interest, and therefore could be used for the repurposing of drugs, thus improving the efficiency of drug development. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3260-7) contains supplementary material, which is available to authorized users.

Helminth infection and dietary intake can affect the intestinal microbiota, as well as the immune system. Here we analyzed the relationship between fecal microbiota and blood profiles of indigenous Malaysians, referred to locally as Orang Asli, in comparison to urban participants from the capital city of Malaysia, Kuala Lumpur. We found that helminth infections had a larger effect on gut microbial composition than did dietary intake or blood profiles. Trichuris trichiura infection intensity also had the strongest association with blood transcriptional profiles. By characterizing paired longitudinal samples collected before and after deworming treatment, we determined that changes in serum zinc and iron levels among the Orang Asli were driven by changes in helminth infection status, independent of dietary metal intake. Serum zinc and iron levels were associated with changes in the abundance of several microbial taxa. Hence, there is considerable interplay between helminths, micronutrients and the microbiota on the regulation of immune responses in humans., Author summary Parasitic intestinal worms and gut bacteria occupy the same space, but we do not understand the nature and scope of their interaction. This is further complicated by dietary effects on the gut bacteria, as well as the immune responses of the host. To better understand these complex interactions, we compared individuals living in indigenous communities in Malaysia, where worm infections are common, with people living in the capital of Malaysia, who were not infected with worms. Data collected included burden of infection, a dietary survey, clinical tests, RNA profiles on blood samples and gut bacteria composition. By collecting data before and after treating the indigenous Malaysians with deworming medication, we could determine what was associated with changes in worm burden following deworming. We found that worm infection had a larger effect on gut bacteria composition than did dietary intake or blood profiles. Worm burden also had the strongest association with blood RNA profiles. We found that zinc and iron levels in the blood were associated with changes in helminth infection status, independent of dietary metal intake. Our results suggest that there is considerable interplay between intestinal worms and gut bacteria with zinc and iron levels in infected people.

Infection with the hepatitis B virus (HBV) may lead to an acute or chronic infection. It is generally accepted that the clinical outcome of infection depends on the balance between host immunity and viral survival strategies. In order to persist, the virus needs to have a high rate of replication and some immune-escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non-fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut-off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five-fold cross-validation. The average prediction accuracy was 61% ± 1%, with a sensitivity of 24% ± 1%, specificity of 98% ± 1%, positive predictive value of 92% ± 4% and negative predictive value of 56% ± 1%. BCP/X, enhancer I and surface/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non-progression to chronic hepatitis. J. Med. Virol. 85:419–424, 2013. © 2013 Wiley Periodicals, Inc.

Background APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. Analysis of tumour samples from women of European descent has shown that germline APOBEC3B deletion is associated with an increased propensity to develop somatic mutations and with an enrichment for immune response-related gene sets. However, this has not been examined in Asian tumour samples, where population differences in genetic and dietary factors may have an impact on the immune system. Methods In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT. Results The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values

Toxoplasma gondii is a public health risk in developing countries, especially those located in the tropics. Widespread infection may inflict a substantial burden on state resources, as patients can develop severe neurological defects and ocular diseases that result in lifelong loss of economic independence. We tested sera for IgG antibody from 493 eye patients in Malaysia. Overall age-adjusted seroprevalence was estimated to be 25% (95% CI: [21%, 29%]). We found approximately equal age-adjusted seroprevalence in Chinese (31%; 95% CI: [25%, 38%]) and Malays (29%; 95% CI: [21%, 36%]), followed by Indians (19%; 95% CI: [13%, 25%]). A logistic regression of the odds for T. gondii seroprevalence against age, gender, ethnicity and the occurrence of six types of ocular diseases showed that only age and ethnicity were significant predictors. The odds for T. gondii seroprevalence were 2.7 (95% CI for OR: [1.9, 4.0]) times higher for a patient twice as old as the other, with ethnicity held constant. In Malays, we estimated the odds for T. gondii seroprevalence to be 2.9 (95% CI for OR: [1.8, 4.5]) times higher compared to non-Malays, with age held constant. Previous studies of T. gondii seroprevalence in Malaysia did not explicitly adjust for age, rendering comparisons difficult. Our study highlights the need to adopt a more rigorous epidemiological approach in monitoring T. gondii seroprevalence in Malaysia.

To assess the agreement of the optical low-coherence reflectometry (OLCR) device LENSTAR LS900 with partial coherence interferometry (PCI) device IOLMaster and applanation and immersion ultrasound biometry. We conducted the study at the Ophthalmology Clinic, University of Malaya Medical Center, Malaysia. Phakic eyes of 76 consecutive cataract patients were measured using four different methods: IOLMaster, LENSTAR and A-scan applanation and immersion ultrasound biometry. We assessed the method agreement in the LENSTAR-IOLMaster, LENSTAR-applanation, and LENSTAR-immersion comparisons for axial length (AL) and intraocular lens (IOL) power using Bland–Altman plots. For average K, we compared LENSTAR with IOLMaster and the TOPCON KR-8100 autorefractor-keratometer. SRK/T formula was used to compute IOL power, with emmetropia as the target refractive outcome. For all the variables studied, LENSTAR agreement with IOLMaster is strongest, followed by those with immersion and applanation. For the LENSTAR-IOLMaster comparison, the estimated proportion of differences falling within 0.33 mm from zero AL and within 1D from zero IOL power is 100%. The estimated proportion of differences falling within 0.5 D from zero average K is almost 100% in the LENSTAR-IOLMaster comparison but 88% in the LENSTAR-TOPCON comparison. The proportion of differences falling within 0.10 mm (AL) and within 1D (IOL power) in the LENSTAR-IOLMaster comparison has practically significant discrepancy with that of LENSTAR-applanation and LENSTAR-immersion comparisons. In phakic eyes of cataract patients, measurements of AL, average K, and IOL power calculated using the SRK/T formula from LENSTAR are biometrically equivalent to those from IOLMaster, but not with those from applanation and immersion ultrasound biometry.

The use of methodologies such as RAPD and AFLP for studying genetic variation in natural populations is widespread in the ecology community. Because data generated using these methods exhibit dominance, their statistical treatment is less straightforward. Several estimators have been proposed for estimating population genetic parameters, assuming simple random sampling and the Hardy-Weinberg (HW) law. The merits of these estimators remain unclear because no comparative studies of their theoretical properties have been carried out. Furthermore, ascertainment bias has not been explicitly modelled. Here, we present a comparison of a set of candidate estimators of null allele frequency (q), locus-specific heterozygosity (h) and average heterozygosity () in terms of their bias, standard error, and root mean square error (RMSE). For estimating q and h, we show that none of the estimators considered has the least RMSE over the parameter space. Our proposed zero-correction procedure, however, generally leads to estimators with improved RMSE. Assuming a beta model for the distribution of null homozygote proportions, we show how correction for ascertainment bias can be carried out using a linear transform of the sample average of h and the truncated beta-binomial likelihood. Simulation results indicate that the maximum likelihood and empirical Bayes estimator of have negligible bias and similar RMSE. Ascertainment bias in estimators of is most pronounced when the beta distribution is J-shaped and negligible when the latter is inverse J-shaped. The validity of the current findings depends importantly on the HW assumption-a point that we illustrate using data from two published studies.

A new generalization of the logarithmic distribution (LD)—the generalized logarithmic distribution (GLD)—is introduced. The GLD is a cluster size distribution of the inverse trinomial distribution, which arises in a generalized random walk problem. Major properties of the GLD are derived and discussed. The method of first moment and frequency of one count and maximum likelihood estimation (MLE) are used for parameter estimation. Rao's score test statistic is derived as a model selection tool. Finally, we demonstrate an application of the GLD in fitting insect data from temperate and tropical regions.

The relationship between acute thermal tolerance and habitat temperature in ectotherm animals informsabout their thermal adaptation and is used to assess thermal safety margins and sensitivity to climatewarming. We studied this relationship in an equatorial freshwater snail (Clea nigricans), belonging to apredominantly marine gastropod lineage (Neogastropoda, Buccinidae). We found that tolerance ofheating and cooling exceeded average daily maximum and minimum temperatures, by roughly 20 °Cineach case. Because habitat temperature is generally assumed to be the main selective factor acting on thefundamental thermal niche, the discordance between thermal tolerance and environmental temperatureimplies trait conservation following ‘in situ’ environmental change, or following novel colonisation of athermally less-variable habitat. Whereas heat tolerance could relate to an historical association with thethermally variable and extreme marine intertidal fringe zone, cold tolerance could associate with eitheran ancestral life at higher latitudes, or represent adaptation to cooler, higher-altitudinal, tropical loticsystems. The broad upper thermal safety margin (difference between heat tolerance and maximumenvironmental temperature) observed in this snail is grossly incompatible with the very narrow safetymargins typically found in most terrestrial tropical ectotherms (insects and lizards), and hence with theemerging prediction that tropical ectotherms, are especially vulnerable to environmental warming. Amore comprehensive understanding of climatic vulnerability of animal ectotherms thus requires greaterconsideration of taxonomic diversity, ecological transition and evolutionary history.& 2014 Elsevier Ltd. All rights reserved.

Sir, We are grateful to Shukla and Singh1 for their comments about our paper.2 We acknowledge their criticisms and apologize for the errors in the references that they pointed out. We had no intention of suggesting that Ocublue Plus (OP) was not approved in the European Union (EU) but, to the best of our knowledge at the time of the study in 2010, only Brilliant Peel (BP) was available in the EU for commercial use. In our study, we compared the neurosensory retinal thickness between OP and controls in the same animal. No direct comparison was done between OP and other groups like BP and ICG. The reduction in neurosensory retinal thickness in the OP group was significant when compared to the controls. This cannot be extrapolated to compare differences between OP and BP. As most of the previous publications on OP came from the institution that is commercially producing and marketing it, we felt that it was important to try to independently compare OP with other commercially available products being used to stain the internal limiting membrane during vitreoretinal surgery. We acknowledge the limitations and shortcomings of this laboratory study but would continue to encourage more work to be done in this field to ensure the safety and efficacy of such products post approval. In light of their comments, we agree that our conclusion that OP caused reduction of the RGC density is not accurate.

Background Mycobacterium abscessus is a rapidly growing mycobacterium that is often associated with human infections. The taxonomy of this species has undergone several revisions and is still being debated. In this study, we sequenced the genomes of 12 M. abscessus strains and used phylogenomic analysis to perform subspecies classification. Results A data mining approach was used to rank and select informative genes based on the relative entropy metric for the construction of a phylogenetic tree. The resulting tree topology was similar to that generated using the concatenation of five classical housekeeping genes: rpoB, hsp65, secA, recA and sodA. Additional support for the reliability of the subspecies classification came from the analysis of erm41 and ITS gene sequences, single nucleotide polymorphisms (SNPs)-based classification and strain clustering demonstrated by a variable number tandem repeat (VNTR) assay and a multilocus sequence analysis (MLSA). We subsequently found that the concatenation of a minimal set of three median-ranked genes: DNA polymerase III subunit alpha (polC), 4-hydroxy-2-ketovalerate aldolase (Hoa) and cell division protein FtsZ (ftsZ), is sufficient to recover the same tree topology. PCR assays designed specifically for these genes showed that all three genes could be amplified in the reference strain of M. abscessus ATCC 19977T. Conclusion This study provides proof of concept that whole-genome sequence-based data mining approach can provide confirmatory evidence of the phylogenetic informativeness of existing markers, as well as lead to the discovery of a more economical and informative set of markers that produces similar subspecies classification in M. abscessus. The systematic procedure used in this study to choose the informative minimal set of gene markers can potentially be applied to species or subspecies classification of other bacteria.

To compare the potential retinal toxicity of two commercially Brilliant blue G dyes (Brilliant Peel and Ocublue Plus) and Indocyanine green (ICG) at usual clinical concentration. Brilliant Peel 0.025% (n=9), Ocublue Plus 0.025% (n=9), and ICG 0.05% (n=9) were injected intravitreally into Sprague–Dawley rat left eyes with balanced salt solution injected in the contralateral eyes as control. Evaluation of the effect of the dyes on retinal architecture was done by histological analysis of neurosensory retinal thickness and retinal ganglion cell (RGC) counts 7 days after intravitreal injection. Paired t-test was done to detect the presence of biologically significant thinning in neurosensory retina and five retinal layers for each dye (paired t-tests). One-way ANOVA and Tukey’s Honestly Significant Difference test were used to assess whether different dyes caused significant thinning in mean neurosensory retinal thickness and reduction of mean RGC density. Eyes treated with ICG had significantly thinner mean total neurosensory retinal thickness compared with the control eyes (P-value=0.01), followed by those treated with Ocublue Plus (P-value=0.03). Brilliant Peel did not cause significant thinning in any of the five retinal layers (all P-values>0.05). No significant difference in mean thinning of the total retinal thickness was detected between dyes (P-value=0.11). The mean thickness of the photoreceptor outer segment and outer plexiform layers were significantly reduced in ICG-injected eyes when compared with the control eyes (P-value=0.02). No significant difference in mean thinning between the three dyes was detected at all five retinal layers using one-way ANOVA (all P-values>0.35). RGC density was significantly reduced for ICG (P-value=0.01) but only marginally for Ocublue Plus (P-value=0.05). No significant reduction in RGC density was observed for Brilliant Peel (P-value=0.2). Intravitreal Brilliant Peel is safe to rats retina. The retinal thinning and reduction in RGC density induced by Ocublue Plus requires further studies to determine the safety profile of this product. Potential retinal toxicity is seen with ICG 0.05%.

To compare homocysteine (Hcy) concentration in the blood plasma, vitreous and aqueous of eyes with proliferative diabetic retinopathy (PDR) against control, and to investigate associations between Hcy concentration in blood plasma with that of aqueous and vitreous in these two groups.Blood plasma, aqueous and vitreous samples were collected during combined cataract and pars plana vitrectomy from 20 eyes with PDR and 21 eyes of patients without diabetes mellitus. Hcy concentration in the samples was determined by chemiluminescent microparticle immunoassay.The mean Hcy concentration (± standard deviation) of blood plasma, vitreous and aqueous were 13.7± 2.2 μmol/l, 3.4±0.7 μmol/l and 1.6±0.3 μmol/l respectively in the PDR group; in the control group, they were 10.4±1.1 μmol/l, 2.6±0.9 μmol/l and 1.2±0.2 μmol/l, respectively. The estimated geometric mean of Hcy concentration of all three variables in the PDR group was about 30% higher than control. In the PDR group, Hcy concentration between the blood plasma and vitreous was significantly associated (ρ=0.71; p-value0.001), as was that between the blood plasma and aqueous (ρ=0.68; p-value0.001). In the control group, only Hcy concentration in the blood plasma and vitreous was significantly associated (ρ=0.66; p-value = 0.001).The geometric mean of Hcy concentration in the blood plasma, vitreous and aqueous of the PDR group was significantly higher than control. The Hcy levels in the blood plasma and vitreous were also significantly associated in both groups. However, the blood plasma and aqueous were significantly associated only in the PDR group.

We wish to suggest the categorical analysis of variance as a means of quantifying the proportion of total genetic variation attributed to different sources of variation. This method potentially challenges researchers to rethink conclusions derived from a well-known method known as the analysis of molecular variance (AMOVA). The CATANOVA framework allows explicit definition, and estimation, of two measures of genetic differentiation. These parameters form the subject of interest in many research programmes, but are often confused with the correlation measures defined in AMOVA, which cannot be interpreted as relative contributions of particular sources of variation. Through a simulation approach, we show that under certain conditions, researchers who use AMOVA to estimate these measures of genetic differentiation may attribute more than justified amounts of total variation to population labels. Moreover, the two measures can also lead to incongruent conclusions regarding the genetic structure of the populations of interest. Fortunately, one of the two measures seems robust to variations in relative sample sizes used. Its merits are illustrated in this paper using mitochondrial haplotype and amplified fragment length polymorphism (AFLP) data.

Background To report the rate of cystoid macular oedema (CMO) as detected by spectral-domain optical coherence tomography (SD-OCT) after intraoperative complication during phacoemulsification. The secondary objectives include comparing mean macular thickness and best-corrected visual acuity (BCVA) between those who developed postoperative CMO against those who did not. Methods This is a prospective cohort study conducted in a tertiary hospital between July 2009 and June 2010. Serial SD-OCT and BCVA were performed at baseline, 1 week, 6 weeks and 16 weeks postoperatively. Results Single eyes from 47 subjects were analyzed; of these 16 (34%) eyes developed CMO. In the CMO group, mean macular thickness (±SD) increased sharply by 56 μm from 273 ± 24 μm at baseline to 329 ± 31 μm at 16 weeks; whereas in the non-CMO group, macular thickness showed a slight increase of 14 μm from 259 ± 21 μm to 272 ± 20 μm. In the CMO group, mean BCVA (in logarithm of minimum angle of resolution) improved modestly from 0.92 ± 0.66 to 0.66 ± 0.41 at week 16; while in the non-CMO group, mean BCVA improved markedly from 0.98 ± 0.59 to 0.21 ± 0.13. The two groups differed significantly in mean macular thickness (p