Variance Reduction for Matrix Computations with Applications to Gaussian Processes

In addition to recent developments in computing speed and memory, methodological advances have contributed to significant gains in the performance of stochastic simulation. In this paper, we focus on variance reduction for matrix computations via matrix factorization. We provide insights into existing variance reduction methods for estimating the entries of large matrices. Popular methods do not exploit the reduction in variance that is possible when the matrix is factorized. We show how computing the square root factorization of the matrix can achieve in some important cases arbitrarily better stochastic performance. In addition, we propose a factorized estimator for the trace of a product of matrices and numerically demonstrate that the estimator can be up to 1,000 times more efficient on certain problems of estimating the log-likelihood of a Gaussian process. Additionally, we provide a new estimator of the log-determinant of a positive semi-definite matrix where the log-determinant is treated as a normalizing constant of a probability density.Comment: 20 pages, 3 figure

Generalized Linear Models via the Lasso: To Scale or Not to Scale?

The Lasso regression is a popular regularization method for feature selection in statistics. Prior to computing the Lasso estimator in both linear and generalized linear models, it is common to conduct a preliminary rescaling of the feature matrix to ensure that all the features are standardized. Without this standardization, it is argued, the Lasso estimate will unfortunately depend on the units used to measure the features. We propose a new type of iterative rescaling of the features in the context of generalized linear models. Whilst existing Lasso algorithms perform a single scaling as a preprocessing step, the proposed rescaling is applied iteratively throughout the Lasso computation until convergence. We provide numerical examples, with both real and simulated data, illustrating that the proposed iterative rescaling can significantly improve the statistical performance of the Lasso estimator without incurring any significant additional computational cost

Column Subset Selection and Nystr\"om Approximation via Continuous Optimization

We propose a continuous optimization algorithm for the Column Subset Selection Problem (CSSP) and Nystr\"om approximation. The CSSP and Nystr\"om method construct low-rank approximations of matrices based on a predetermined subset of columns. It is well known that choosing the best column subset of size $k$ is a difficult combinatorial problem. In this work, we show how one can approximate the optimal solution by defining a penalized continuous loss function which is minimized via stochastic gradient descent. We show that the gradients of this loss function can be estimated efficiently using matrix-vector products with a data matrix $X$ in the case of the CSSP or a kernel matrix $K$ in the case of the Nystr\"om approximation. We provide numerical results for a number of real datasets showing that this continuous optimization is competitive against existing methods

Data from: Cross-species screening of microsatellite markers for individual identification of snow petrel Pagodroma nivea and Wilson’s storm petrel Oceanites oceanicus in Antarctica

Seabirds are important indicators of marine ecosystem health. Species within the order Procellariiformes are the most abundant seabird species group distributed from warm tropical to cold temperate regions including Antarctica. There is a paucity of information on basic biology of the pelagic seabird species nesting on the Antarctic continents, and long-term studies are required to gather data on their population demography, genetics and other ecological parameters. Under the ‘Biology and Environmental Sciences’ component of the Indian Antarctic programme, long-term monitoring of Antarctic biodiversity is being conducted. In this paper, we describe results of cross-species screening of a panel of 12 and 10 microsatellite markers in two relatively little studied seabird species in Antarctica, the snow petrel Pagodroma nivea and the Wilson's storm petrel Oceanites oceanicus, respectively. These loci showed high amplification success and moderate levels of polymorphism in snow petrel (mean no. of alleles 7.08 ± 3.01 and mean observed heterozygosity 0.35 ± 0.23), but low polymorphism in Wilson's storm petrel (mean no. of alleles 3.9 ± 1.3 and mean observed heterozygosity 0.28 ± 0.18). The results demonstrate that these panels can unambiguously identify individuals of both species (cumulative PIDsibs for snow petrel is 3.7 × 10−03 and Wilson's storm petrel is 1.9 × 10−02) from field-collected samples. This work forms a baseline for undertaking long-term genetic research of these Antarctic seabird species and provides critical insights into their population genetics

p40 & thyroid transcription factor-1 immunohistochemistry: A useful panel to characterize non-small cell lung carcinoma-not otherwise specified (NSCLC-NOS) category

Background & objectives: Accurate histopathological subtyping of non-small cell lung carcinoma (NSCLC) is essential for targeted therapeutic agents. Immunohistochemistry (IHC) is helpful in identification of different tumour subtypes. In this study two marker approaches, one each for glandular and squamous cell differentiation was applied to maximize the proportion of accurately subtyped NSCLC not otherwise specified (NOS) tumours on small biopsy samples. Methods: Two hundred and sixty three consecutive lung biopsies of primary lung carcinoma were prospectively studied. These were subtyped first morphologically and then by IHC for p40 and thyroid transcription factor-1 (TTF-1). The diagnosis of NSCLC-NOS before and after addition of IHC was evaluated. Results were correlated and validated with morphologically proven cases and matched surgical specimens. Results: Based on morphology, only 140 of the 263 (53.2%) cases of NSCLC were characterized, whereas 123 (46.7%) were classified as NSCLC-NOS type. With addition of IHC (p40 and TTF-1), the latter category reduced to 14.4 per cent and a sum of 225 (85.5%) cases were accurately subtyped into squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma. p40 showed 100 per cent sensitivity and specificity for squamous differentiation whereas TTF-1 showed sensitivity of 85.3 per cent and specificity of 98.1 per cent. Ninety per cent correlation of morphologic subtypes was achieved with matched resected specimens. Interpretation & conclusions: Our results showed that an approach of using only a two-antibody panel (p40 and TTF-1) might help in reduction of diagnostic category of NSCLC-NOS significantly and contribute in saving tissue for future molecular testing

Pande et al_2018_microsatellite

Genotype data generated from cross-species microsatellite markers for Snow Petrel and Wilson's Storm Petrel

Utility of conventional transbronchial needle aspiration with rapid on-site evaluation (c-TBNA-ROSE) at a tertiary care center with endobronchial ultrasound (EBUS) facility

Background: Conventional transbronchial needle aspiration (c-TBNA) is an underutilized bronchoscopic modality. Endobronchial ultrasound (EBUS) guided-TBNA though efficacious is an expensive modality, facilities of which are available at only limited centers. c-TBNA is cost-effective and has potential for wide utilization especially in resource-limited settings. Rapid on-site evaluation (ROSE) improves the yield of c-TBNA. Materials and Methods: A retrospective review of the bronchoscopy records (May 2012 to July 2014) was performed. The patients who underwent c-TBNA with ROSE were included in the study and their clinical details were extracted. Convex probe EBUS-TBNA was being regularly performed during the study period by the operators performing c-TBNA. Results: c-TBNA with ROSE was performed in 41 patients with mean age of 42.4 (16.2) years. The most frequently sampled node stations (>90% patients) were the subcarinal and lower right paratracheal. Representative samples could be obtained in 33 out of the 41 patients (80.4%). c-TBNA was diagnostic in 32 [tuberculosis (TB)-8, sarcoidosis-9, and malignancy-15] patients out of the 41 patients. The overall diagnostic yield (sensitivity) of c-TBNA with ROSE was 78%. Mean procedure duration was 18.4 (3.1) min and there were no procedural complications. Conclusion: c-TBNA with ROSE is a safe, efficacious, and cost-effective bronchoscopic modality. When it was performed by operators routinely performing EBUS-TBNA, diagnostic yields similar to that of EBUS-TBNA can be obtained. Even at the centers where EBUS facilities are available, c-TBNA should be routinely performed

Amifostine Analog, DRDE-30, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

Bleomycin (BLM) is an effective curative option in the management of several malignancies including pleural effusions; but pulmonary toxicity, comprising of pneumonitis and fibrosis, poses challenge in its use as a front-line chemotherapeutic. Although Amifostine has been found to protect lungs from the toxic effects of radiation and BLM, its application is limited due to associated toxicity and unfavorable route of administration. Therefore, there is a need for selective, potent, and safe anti-fibrotic drugs. The current study was undertaken to assess the protective effects of DRDE-30, an analog of Amifostine, on BLM-induced lung injury in C57BL/6 mice. Whole body micro- computed tomography (CT) was used to non-invasively observe tissue damage, while broncheo-alveolar lavage fluid (BALF) and lung tissues were assessed for oxidative damage, inflammation and fibrosis. Changes in the lung density revealed by micro-CT suggested protection against BLM-induced lung injury by DRDE-30, which correlated well with changes in lung morphology and histopathology. DRDE-30 significantly blunted BLM-induced oxidative stress, inflammation and fibrosis in the lungs evidenced by reduced oxidative damage, endothelial barrier dysfunction, Myeloperoxidase (MPO) activity, pro-inflammatory cytokine release and protection of tissue architecture, that could be linked to enhanced anti-oxidant defense system and suppression of redox-sensitive pro-inflammatory signaling cascades. DRDE-30 decreased the BLM-induced augmentation in BALF TGF-β and lung hydroxyproline levels, as well as reduced the expression of the mesenchymal marker α-smooth muscle actin (α-SMA), suggesting the suppression of epithelial to mesenchymal transition (EMT) as one of its anti-fibrotic effects. The results demonstrate that the Amifostine analog, DRDE-30, ameliorates the oxidative injury and lung fibrosis induced by BLM and strengthen its potential use as an adjuvant in alleviating the side effects of BLM

Evaluation of epidermal growth factor receptor mutations based on mutation specific immunohistochemistry in non-small cell lung cancer: a preliminary study

Background & objectives: Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC). Methods: Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed. Results: Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases. Interpretation & conclusions: In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests