The Validity, Generalizability and Feasibility of Summative Evaluation Methods in Visual Analytics

Many evaluation methods have been used to assess the usefulness of Visual Analytics (VA) solutions. These methods stem from a variety of origins with different assumptions and goals, which cause confusion about their proofing capabilities. Moreover, the lack of discussion about the evaluation processes may limit our potential to develop new evaluation methods specialized for VA. In this paper, we present an analysis of evaluation methods that have been used to summatively evaluate VA solutions. We provide a survey and taxonomy of the evaluation methods that have appeared in the VAST literature in the past two years. We then analyze these methods in terms of validity and generalizability of their findings, as well as the feasibility of using them. We propose a new metric called summative quality to compare evaluation methods according to their ability to prove usefulness, and make recommendations for selecting evaluation methods based on their summative quality in the VA domain.Comment: IEEE VIS (VAST) 201

Acute Tubular Necrosis and Interstitial Nephritis during Pemetrexed Therapy

We report a patient with unknown primary undifferentiated carcinoma who developed acute renal failure associated with interstitial fibrosis following pemetrexed therapy. Despite drug withdrawal, renal function remained altered and the patient experienced chronic renal insufficiency. Pemetrexed disodium (Alimta™) is a multitargeted antifolate agent approved by the Food and Drug Administration (FDA) for patients diagnosed with mesothelioma and non-small cell lung cancer. This drug is almost exclusively cleared by renal excretion [1]. The most common side effects are hematologic dose-limiting toxicities and nonhematologic toxicities including fatigue, diarrhea, nausea, mucositis and rash. Although few cases of renal failure have been published, no study has reported on the renal pathological findings in this setting. We present a case of acute tubular necrosis associated with interstitial fibrosis after pemetrexed therapy

Long-Term Survival in Gastroesophageal Junction Adenocarcinoma: Ramucirumab

We report a case of long-term survival with complete response of liver metastases within RAINBOW, a randomized, controlled trial of ramucirumab 8 mg/kg intravenously (days 1, 15) versus placebo, both plus paclitaxel 80 mg/m2 intravenously (days 1, 8, 15), every 4 weeks in patients with previously treated advanced gastroesophageal junction adenocarcinoma. A 64-year-old man with gastroesophageal junction adenocarcinoma and liver metastases received first-line folinic acid, 5-fluorouracil plus oxaliplatin (FOLFOX) following jejunostomy. On liver progression, he enrolled in RAINBOW (April 2012), receiving ramucirumab. In November 2013, positron emission tomography scan was consistent with complete metabolic response, confirmed by a follow-up scan in March 2016

Drifter technique: a new method to obtain metaphases in Hep-2 cell line cultures

The Hep-2 cell line is derived from laryngeal carcinoma cells and is often utilized as a model in carcinogenesis and mutagenesis tests. To evaluate the proliferative potential of this line, we developed a cytogenetic methodology (drifter technique) to obtain metaphases from cells that loose cellular adhesion when they underwent mitosis in culture. By this procedure, 2000 cells were counted, resulting in a mitotic index (MI) of 22.2%. Although this MI was not statistically different from the one obtained using either a classical cytogenetic method or a cell synchronization technique, the drifter technique has the advantage of not requiring the use of some reagents for the obtention of metaphases and also of diminishing the consumption of maintenance reagents for this cell line.A linhagem celular Hep-2 é formada por células de carcinoma da laringe e é muito utilizada em modelos de carcinogênese e mutagenêse. Para avaliar o potencial proliferativo desta linhagem, desenvolvemos uma metodologia citogenética (técnica do sobrenadante) para obtenção de metáfases a partir de células que, ao entrarem em mitose, perdem adesão celular, ficando em suspensão no meio de cultura. Através deste procedimento, foram contadas 2000 células, correspondendo a um índice mitótico (IM) de 22.2% . Apesar de o IM obtido por esta técnica não ter sido estatisticamente diferente do IM obtido por outras metodologias citogenéticas clássicas, a técnica do sobrenadante é vantajosa porque elimina o uso de alguns reagentes utilizados na obtenção de metáfases e também diminui o consumo de reagentes de manutenção desta linhagem.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal do Pará Centro de Ciências Biológicas Departamento de BiologiaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de GenéticaUniversidade Federal do Pará Centro de Ciências Biológicas Departamento de GenéticaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MorfologiaUNIFESP, EPM, Depto. de MorfologiaSciEL

A multicenter randomized phase IIb efficacy study of Vx-001, a peptide-based cancer vaccine as maintenance treatment in advanced non-smallcell lung cancer: treatment rationale and protocol dynamics. Clin Lung Cancer 2013

Abstract We present the treatment rationale and study design of a multicenter, open-label, randomized, 2-arm, phase IIb study. Patients with stage IV or recurrent stage I to III non-small-cell lung cancer (NSCLC) whose disease does not progress after 4 cycles of first-line platinum-based chemotherapy will be randomized in a 1:1 ratio to 1 of 2 study arms. Patients will receive the cancer vaccine Vx-001 ϩ Montanide ISA51 VG (Seppic, Paris, France) adjuvant subcutaneously, at a dose of 2 mg, or placebo ϩ Montanide ISA51 VG adjuvant subcutaneously. The vaccination protocol comprises 2 injections with the TYR-Vx001 or placebo (1 at day 0 and another at week 3) and 4 injections with the ARG-Vx001 or placebo, at weeks 6, 9, 12, and 15. After the treatment assessment at week 18, patients will receive the ARG-Vx001 or placebo every 12 weeks starting from week 27 until disease progression, unacceptable toxicity, withdrawal of informed consent, or death. The primary end point of this study is the survival rate at 12 months. Secondary end points include time-to-event comparison of overall survival and comparison of time to treatment failure. Exploratory objectives include comparison of disease control rate after the end of subsequent second-line treatments, comparisons of vaccine immune responses, comparison of survival rate at 12 months in patients with vaccine-induced immune response detected after the second and sixth injections, identification of biomarkers on lymphocytes and on tumors, and comparison of safety and tolerability

WISE/NEOWISE observations of Active Bodies in the Main Belt

We report results based on mid-infrared photometry of 5 active main belt objects (AMBOs) detected by the Wide-field Infrared Survey Explorer (WISE) spacecraft. Four of these bodies, P/2010 R2 (La Sagra), 133P/Elst-Pizarro, (596) Scheila, and 176P/LINEAR, showed no signs of activity at the time of the observations, allowing the WISE detections to place firm constraints on their diameters and albedos. Geometric albedos were in the range of a few percent, and on the order of other measured comet nuclei. P/2010 A2 was observed on April 2-3, 2010, three months after its peak activity. Photometry of the coma at 12 and 22 {\mu}m combined with ground-based visible-wavelength measurements provides constraints on the dust particle mass distribution (PMD), dlogn/dlogm, yielding power-law slope values of {\alpha} = -0.5 +/- 0.1. This PMD is considerably more shallow than that found for other comets, in particular inbound particle fluence during the Stardust encounter of comet 81P/Wild 2. It is similar to the PMD seen for 9P/Tempel 1 in the immediate aftermath of the Deep Impact experiment. Upper limits for CO2 & CO production are also provided for each AMBO and compared with revised production numbers for WISE observations of 103P/Hartley 2.Comment: 32 Pages, including 5 Figure

Investigating cat predation as the cause of bat wing tears using forensic DNA analysis

Cat predation upon bat species has been reported to have significant effects on bat populations in both rural and urban areas. The majority of research in this area has focussed on observational data from bat rehabilitators documenting injuries, and cat owners, when domestic cats present prey. However, this has the potential to underestimate the number of bats killed or injured by cats. Here, we use forensic DNA analysis techniques to analyze swabs taken from injured bats in the United Kingdom, mainly including Pipistrellus pipistrellus (40 out of 72 specimens). Using quantitative PCR, cat DNA was found in two‐thirds of samples submitted by bat rehabilitators. Of these samples, short tandem repeat analysis produced partial DNA profiles for approximately one‐third of samples, which could be used to link predation events to individual cats. The use of genetic analysis can complement observational data and potentially provide additional information to give a more accurate estimation of cat predation

Treatment of autosomal dominant hypocalcemia Type 1 with the calcilytic NPSP795 (SHP635)

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain‐of‐function mutations of the calcium‐sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1. Five adults with ADH1 due to 4 distinct CAR mutations received escalating doses of the calcilytic compound NPSP795 (SHP635) on 3 consecutive days. Pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed. Parallel in vitro testing with subject CaR mutations assessed the effects of NPSP795 on cytoplasmic calcium concentrations (Ca2+i), and ERK and p38MAPK phosphorylation. These effects were correlated with clinical responses to administration of NPSP795. NPSP795 increased plasma PTH levels in a concentration‐dependent manner up to 129% above baseline (p=0.013) at the highest exposure levels. Fractional excretion of calcium (FECa) trended down but not significantly so. Blood ionized calcium levels remained stable during NPSP795 infusion despite fasting, no calcitriol and little calcium supplementation. NPSP795 was generally safe and well‐tolerated. There was significant variability in response clinically across genotypes. In vitro, all mutant CaRs were half‐maximally activated (EC50) at lower concentrations of extracellular calcium (Ca2+o) compared to wild type (WT) CaR; NPSP795 exposure increased the EC50 for all CaR activity readouts. However, the in vitro responses to NPSP795 did not correlate with any clinical parameters. NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose‐dependent manner, and thus, serves as proof‐of‐concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype, or the response to calcilytics, suggesting that other parameters impact the response to the drug

A Universal Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA Libraries from High-Containment RNA Viruses

ABSTRACT Several biosafety level 3 and/or 4 (BSL-3/4) pathogens are high-consequence, single-stranded RNA viruses, and their genomes, when introduced into permissive cells, are infectious. Moreover, many of these viruses are select agents (SAs), and their genomes are also considered SAs. For this reason, cDNAs and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral RNA before transfer out of the BSL-3/4 and/or SA laboratory. This tremendously limits the capacity to conduct viral genomic research, particularly the application of next-generation sequencing (NGS). Here, we present a sequence-independent method to rapidly amplify viral genomic RNA while simultaneously abolishing both viral and genomic RNA infectivity across multiple single-stranded positive-sense RNA (ssRNA+) virus families. The process generates barcoded DNA amplicons that range in length from 300 to 1,000 bp, which cannot be used to rescue a virus and are stable to transport at room temperature. Our barcoding approach allows for up to 288 barcoded samples to be pooled into a single library and run across various NGS platforms without potential reconstitution of the viral genome. Our data demonstrate that this approach provides full-length genomic sequence information not only from high-titer virion preparations but it can also recover specific viral sequence from samples with limited starting material in the background of cellular RNA, and it can be used to identify pathogens from unknown samples. In summary, we describe a rapid, universal standard operating procedure that generates high-quality NGS libraries free of infectious virus and infectious viral RNA. IMPORTANCE This report establishes and validates a standard operating procedure (SOP) for select agents (SAs) and other biosafety level 3 and/or 4 (BSL-3/4) RNA viruses to rapidly generate noninfectious, barcoded cDNA amenable for next-generation sequencing (NGS). This eliminates the burden of testing all processed samples derived from high-consequence pathogens prior to transfer from high-containment laboratories to lower-containment facilities for sequencing. Our established protocol can be scaled up for high-throughput sequencing of hundreds of samples simultaneously, which can dramatically reduce the cost and effort required for NGS library construction. NGS data from this SOP can provide complete genome coverage from viral stocks and can also detect virus-specific reads from limited starting material. Our data suggest that the procedure can be implemented and easily validated by institutional biosafety committees across research laboratories