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An effective approach to solving complex problems is to decompose them and integrate dedicated solvers for those subproblems. We introduce a hybrid decomposition that incorporates: (1) a quantum annealer that samples from the configuration space of a relaxed problem to obtain strong candidate solutions, and (2) a classical processor that maintains a global search tree and enforces constraints on the relaxed components of the problem. Our framework is the first to use quantum annealing as part of a complete search. We consider variants of our approach with differing amounts of guidance from the quantum annealer. We empirically test our algorithm and compare the variants on problems from three scheduling domains: graph-coloring-type scheduling, simplified Mars Lander task scheduling, and airport runway scheduling. While we were only able to test on problems of small sizes, due to the limitation of currently available quantum annealing hardware, the empirical results show that results obtained from the quantum annealer can be used for more effective search node pruning and to improve node selection heuristics when compared to a standard classical approach.

This article examines the predominately Asian American “Anti-Phandom” community on GuruGossiper.com to explore how anti-fans of YouTube star Michelle Phan engage with ideologies of beauty cultures within Asian diasporic contexts. For many, Anti-Phandom provides an online space where personal concerns about female Asian beauty standards can be negotiated through Michelle Phan. Within these conversations, I argue Anti-Phans display forms of resistance to Phan's postfeminist forms of female empowerment on racial and ethnic terms. However, these counters to Phan's notions of beauty also produce a rubric of the beautiful Asian woman which renders difference as ugly, creating idealized definitions of racial beauty and Asian/American cultures based on essentialized categories that police diasporic women.

Debuting in the fall of 2017, the Second Wave podcast follows host Thanh Tan as she explores the experiences and challenges of U.S.-born Vietnamese Americans. Similar to many children of Vi...

Brain metastases (BM) are a leading cause of cancer death and prognosis remains poor despite treatment advances at other sites. Models are central to therapeutic development, but few orthotopic patient-derived xenograft (PDX) models of BM exist. To represent diversity across BM types, we established a program to create orthotopic PDX at scale from all BM patients. To date BM were received from 100 patients and PDX attempted by direct brain injection (PDX, n=89) or injection of low passage patient-derived cell lines (PDCLX, n=11). We created 65 successful BM PDX from 13 cancers: 17 lung (55% take), 15 breast (68%), 6 melanoma (75%), 5 CNS lymphoma (83%), 3 gastrointestinal (75%), 2 esophageal (40%), 2 ovarian (67%), 1 sarcoma (100%), 1 laryngeal (100%), 1 prostate (100%), 1 pancreatic (100%), 1 uterine adenosarcoma (100%), and 1 yolk sac tumor (100%). Take rate was similar for models derived from patients with prior chemotherapy-only versus immune/targeted therapy-only (63 vs 58%). Fifteen patients had live tumor and matching PBMCs archived for modeling in vitro immunotherapy responses. Mean time to moribund among different cancer types ranged from 27 days (yolk sac tumor) to 177.5 days (ovarian). BM PDX had a favorable timeline for preclinical study (90% moribund at 180 days). All PDX retained high fidelity to the patient driver SNVs and copy aberrations, even at >P4. No significant differences noted by immunodeficient strain (SCID versus NSG) or injection site (orthotopic versus heterotopic). Explants from BM PDX were able to generate long-term cell lines (60%) or short-term cultures with qualitative concordance of model-to-patient responses to targeted therapy (Osimertinib, EGFRi) and immunotherapy (Pembrolizumab, PD1i). Genomic and clinical data were used to create the DFCI BM PDX cBioPortal for public release and models distribution will be available through the DFCI Center for Patient Derived Models.

Impaired adipose tissue function and lower levels of high density lipoprotein cholesterol (HDL-C) have been implicated in the development of vascular dementia, and metabolic diseases such as hypertension, atherosclerosis, type 2 diabetes (T2D) and metabolic syndrome. Interestingly, both the substrate fluxes in adipose tissue and HDL-C concentration differ between men and women. Moreover, adipose tissue cholesterol efflux has been implicated in modulation of HDL-C levels. Thus, we aimed to determine if the association between serum estradiol levels and adipose tissue cholesterol efflux is sex-dependent.We evaluated the serum estradiol levels and adipose tissue cholesterol efflux in young healthy men (n=5) and women (n=3). Adipose tissue cholesterol efflux was determined using subcutaneous microdialysis probes. Linear regression analyses were used to determine the relationship between the parameters, p0.05 was considered as statistically significant.Our data demonstrated that serum estradiol levels directly associated with adipose tissue cholesterol efflux; however, the relationships may be sex-dependent. We discussed our results in the context of currently available data regarding sex-dependent variability in adipose tissue function and HDL-C metabolism as a potential contributor to higher rates of vascular dementia in men. Further research is required to understand the sex-dependent and -independent variabilities in adipose tissue metabolism to determine novel targets for interventions to prevent the development of vascular dementia.

We investigate solvable-unsolvable phase transitions in the single-machine scheduling (SMS) problem. SMS is at the core of practical problems such as telescope and satellite scheduling and manufacturing. To study the solvability phase transition, we construct a variety of instance families parameterized by the set of the processing times, the window size (deadline minus release time), and the horizon. We empirically establish the phase transition and look for an easy-hard-easy pattern for this family using several common solvers. While in many combinatorial problems a phase transition coincides with typically hard instances, whether or not that is the case with SMS remains an open question, and merits further study.

The GEO-Stationary Coastal and Air Pollution Events (GEO-CAPE) mission plans to put a visible spectrum imaging instrument on a satellite in geo-stationary orbit to perform ocean color remote sensing. Two different instrument designs, Filter Radiometer (FR) and COastal Ecosystems Dynamic Imager (COEDI), with different shape for the imaged area and image acquisition time, are being evaluated. Scheduling observations for either instrument requires optimizing science objectives in the presence of predicted cloud cover and available daylight. We model this scheduling problem as both Mixed Integer Linear Program (MILP) and Constraint Programming (CP) problems, and compare these two formulations for FR and COEDI using real cloudiness data collected at different times throughout the year. Our results show that MILP is the more suitable technique, and the schedule quality metric shows FR is the preferred design. We have reported our results to the GEO-CAPE mission team to assist them making an informed decision for the next step in formulating this mission.

Lymphomas of the central nervous system (CNSL) are rare tumors with few treatment options; however, recent genomic studies have uncovered several druggable targets. To facilitate novel treatment discovery, we sought to establish patient-derived xenograft (PDX) models and cell lines from patients with newly diagnosed or recurrent CNSL. PDX models were attempted from fresh tumor samples from 18 consented patients for whom rich clinical annotation was available. Orthotopic intracranial injections were performed via stereotactic injection. Cell line generation was attempted from both primary tumors (PDCL) and PDX samples (PDXCL). Characterization included histopathology, targeted exome sequencing, low-pass whole-genome sequencing for copy number evaluation, and expression profiling of matched patient tumors and PDXs. Drug response testing was performed using CellTiterGlo. From 18 samples attempted, 8 PDX models were successfully generated: 2 primary CNS diffuse large B-cell lymphoma (DLBCL), 5 secondary CNS DLBCL, and 1 secondary cutaneous T-cell lymphoma (CTCL). Mean time to moribund was 66 days. All 8 PDXs grew successfully as orthotopic models, and 4 also grew in subrenal capsule. Additionally, 6 PDCL and 2 PDXCL were established (> P3). Models faithfully represented primaries, showing nearly identical histopathology, immunoprofiles, and genomic signatures. To support expanded and rapid preclinical use of these models in drug testing we documented that PDX could be explanted to create short-term cell preparations or long-term cell lines with a 100% and 40% success rate, respectively. Proof of principle testing showed that explanted DLBCL PDX cells and cell lines showed sensitivity to copanlisib and venetoclax, which were not efficacious in the CTCL PDX. These findings showcase a diverse collection of CNSL models demonstrating high fidelity to primary tumors at the genomic and phenotypic levels, emphasizing their utility for preclinical studies and as patient avatars to rapidly determine sensitivities to existing and novel regimens prior to initiation of therapy.

Brain metastases (BM) are a leading cause of cancer death and prognosis remains poor despite treatment advances at other sites. Models are central to therapeutic development, but few orthotopic patient-derived xenograft (PDX) models of BM exist. To represent diversity across BM types, we established a program to create orthotopic PDX at scale from all BM patients. To date BM were received from 100 patients and PDX attempted by direct brain injection (PDX, n=89) or injection of low passage patient-derived cell lines (PDCLX, n=11). We created 65 successful BM PDX from 13 cancers: 17 lung (55% take), 15 breast (68%), 6 melanoma (75%), 5 CNS lymphoma (83%), 3 gastrointestinal (75%), 2 esophageal (40%), 2 ovarian (67%), 1 sarcoma (100%), 1 laryngeal (100%), 1 prostate (100%), 1 pancreatic (100%), 1 uterine adenosarcoma (100%), and 1 yolk sac tumor (100%). Take rate was similar for models derived from patients with prior chemotherapy-only versus immune/targeted therapy-only (63 vs 58%). Fifteen patients had live tumor and matching PBMCs archived for modeling in vitro immunotherapy responses. Mean time to moribund among different cancer types ranged from 27 days (yolk sac tumor) to 177.5 days (ovarian). BM PDX had a favorable timeline for preclinical study (90% moribund at 180 days). All PDX matched the patient driver SNVs and copy aberrations, even at >P4. No significant differences noted by immunodeficient strain (SCID versus NSG) or injection site (orthotopic versus heterotopic). Explants from BM PDX were able to generate long-term cell lines (60%) or short-term cultures with qualitative concordance of model-to-patient responses to targeted therapy (Osimertinib, EGFRi) and immunotherapy (Pembrolizumab, PD1i). Genomic and clinical data were used to create the DFCI BM PDX cBioPortal for public release and models distribution will be available through the DFCI Center for Patient Derived Models.

PurposeWe explored the diagnostic use of circulating tumor cells in patients with neoadjuvant bladder cancer using enumeration and next generation sequencing.Materials and methodsA total of 20 patients with bladder cancer who were eligible for cisplatin based neoadjuvant chemotherapy were enrolled in an institutional review board approved study. Subjects underwent blood draws at baseline and after 1 cycle of chemotherapy. A total of 11 patients with metastatic bladder cancer and 13 healthy donors were analyzed for comparison. Samples were enriched for circulating tumor cells using the novel IsoFlux™ System microfluidic collection device. Circulating tumor cell counts were analyzed for repeatability and compared with Food and Drug Administration cleared circulating tumor cells. Circulating tumor cells were also analyzed for mutational status using next generation sequencing.ResultsMedian circulating tumor cell counts were 13 at baseline and 5 at followup in the neoadjuvant group, 29 in the metastatic group and 2 in the healthy group. The concordance of circulating tumor cell levels, defined as low-fewer than 10, medium-11 to 30 and high-greater than 30, across replicate tubes was 100% in 15 preparations. In matched samples the IsoFlux test showed 10 or more circulating tumor cells in 4 of 9 samples (44%) while CellSearch® showed 0 of 9 (0%). At cystectomy 4 months after baseline all 3 patients (100%) with medium/high circulating tumor cell levels at baseline and followup had unfavorable pathological stage disease (T1-T4 or N+). Next generation sequencing analysis showed somatic variant detection in 4 of 8 patients using a targeted cancer panel. All 8 cases (100%) had a medium/high circulating tumor cell level with a circulating tumor cell fraction of greater than 5% purity.ConclusionsThis study demonstrates a potential role for circulating tumor cell assays in the management of bladder cancer. The IsoFlux method of circulating tumor cell detection shows increased sensitivity compared with CellSearch. A next generation sequencing assay is presented with sufficient sensitivity to detect genomic alterations in circulating tumor cells.

Classically, scheduling research in artificial intelligence has concentrated on the combinatorial challenges arising in a large, static domain where the set of jobs, resource capacities, and other problem parameters are known with certainty and do not change. In contrast, queueing theory has focused primarily on the stochastic arrival and resource requirements of new jobs, de-emphasizing the combinatorics. We study a dynamic parallel scheduling problem with sequence-dependent setup times: arriving jobs must be assigned (online) to one of a set of resources. The jobs have different service times on different resources and there exist setup times that are required to elapse between jobs, depending on both the resource used and the job sequence. We investigate four models that hybridize a scheduling model with techniques from queueing theory to address the dynamic problem. We demonstrate that one of the hybrid models can significantly reduce observed mean flow time performance when compared to the pure scheduling and queueing theory methods. More specifically, at high system loads, our hybrid model achieves a 15% to 60% decrease in mean flow time compared to the pure methodologies. This paper illustrates the advantages of integrating techniques from queueing theory and scheduling to improve performance in dynamic problems with complex combinatorics.

Stability analysis consists of identifying conditions under which the number of jobs in a system is guaranteed to remain bounded over time. To date, such long-run performance guarantees have not been available for periodic approaches to dynamic scheduling problems. However, stability has been extensively studied in queueing theory. In this paper, we introduce stability to the dynamic scheduling literature and demonstrate that stability guarantees can be obtained for methods that build the schedule for a dynamic problem by periodically solving static deterministic sub-problems. Specifically, we analyze the stability of two dynamic environments: a two-machine flow shop, which has received significant attention in scheduling research, and a polling system with a flow-shop server, an extension of systems typically considered in queueing. We demonstrate that, among stable policies, methods based on periodic optimization of static schedules may achieve better mean flow times than traditional queueing approaches.

We compare the outcomes of 2 models of physician-initiated rapid HIV testing in an emergency department (ED).One-year retrospective cohort comparing 2 6-month models of physician-initiated rapid HIV testing, point-of-care versus laboratory. Patients aged 12 years or older and able to give verbal consent were eligible for physician-initiated rapid HIV testing if their treating physician believed testing was clinically indicated. During the point-of-care phase, nursing staff performed oral fluid testing. During the laboratory phase, the laboratory performed whole-blood testing. The proportion of potentially eligible patients who had physician-initiated rapid HIV testing ordered (order rate), proportion of ordered tests completed (test completion rate), and proportion of potentially eligible patients who completed testing (overall testing rate) during each phase were assessed. ED length of stay and testing times were also compared.For the point-of-care versus laboratory phase, respectively, there were 24,345 potentially eligible patients versus 26,363; order rate was 3.3% versus 2.4% (P.001); test completion rate was 75.3% versus 86.8% (P.001); overall testing rate was 2.5% versus 2.1% (P=.009). Eighteen (3.0%) of the point-of-care-tested patients and 15 (2.7%) of the laboratory-tested patients had reactive tests (P=0.02). The total testing time was greater in the laboratory phase (88 versus 66 minutes; P.001); however, there was no significant difference in the length of stay between phases (6.2 versus 6.9 hours; P=.15).Relatively few ED patients undergo physician-initiated rapid HIV testing regardless of whether a point-of-care or laboratory approach is used. Differences exist in most outcome measures when point-of-care and laboratory models are compared, which should be considered when testing is implemented.

The nucleoside analog R1479 is a potent and highly selective inhibitor of NS5b-directed hepatitis C virus (HCV) RNA polymerase in vitro. Because of its limited permeability, lipophilic prodrugs of R1479 were screened. Selection of the prodrug involved optimization of solubility, permeability, and stability parameters. R1626 has dissociation constant, intrinsic solubility, log partition coefficient (n-octanol water), and Caco-2 permeability of 3.62, 0.19 mg/mL, 2.45, and 14.95 x 10(-6) cm/s, respectively. The hydrolysis of the prodrug is significantly faster in the Caco-2 experiments than in hydrolytic experiments, suggesting that the hydrolysis is catalyzed by enzymes in the cellular membrane. Using GastroPlus, the physical properties of R1626 successfully predict the dose dependence of the pharmacokinetics in humans previously studied. The program predicts that if the particle size of R1626 is less than 25 microm, it will be well absorbed. Prodrugs with a solubility of greater than 100 microg/mL and permeability in the Caco-2 assay greater than 3 x 10(-6) cm/s are expected to achieve a high fraction absorbed.

This article uses scaled entity search (SES), a data mining technique and interpretive framework, to study the historically dynamic role of local radio broadcasters in the United States. The authors model the technique by searching for more than two thousand individual radio call letters and discussing the call signs with the highest number of page hits, with critical attention to the meaning of those results within the 1.6 million page digitized corpus of the Media History Digital Library. They also detail the strategies of one of the top-trending stations, WCCO Minneapolis, to distinguish itself in the broadcasting marketplace through the trade press. The authors conclude that WCCO’s emphasis on various aspects of the local market through facts and figures, constructions of local market identity, and relationships with sponsors instantiated a larger trend on the part of local broadcasters to position themselves favorably to advertisers and other industry participants.

Endogenous mechanisms underlying the remodeling of neuronal circuitry after mammalian CNS injury or disease remain primarily unknown. Here, we investigated axonal plasticity after optic nerve injury and found that macrophages recruited into the injury site and adult retinal ganglion cell (RGC) axons, which undergo injury-induced sprouting and terminal remodeling, were linked by their respective expression of a ligand and receptor pair active in axon guidance. Recruited macrophages specifically upregulated mRNA encoding the guidance molecule EphB3 and expressed EphB proteins capable of binding Ephrin B moleculesin vivoandin vitro. Injured adult RGC axons in turn expressed EphrinB3, a known receptor for EphB3, and RGC axons bound recombinant EphB3 protein injected into the optic nerve.In vitro, EphB3 supported adult RGC axon outgrowth, and axons turned toward a source of this guidance molecule.In vivo, both reduction of EphB3 function in adult heterozygous animals and loss of function in homozygous animals greatly decreased RGC axon re-extension or sprouting after optic nerve injury. Comparisons of axon re-extension in EphB3 null and wild-type littermates showed that this loss of axonal plasticity was not attributable to a difference in intrinsic axon growth potential. Rather, the results indicated an essential role for local optic nerve-derived EphB3 in regulating adult RGC axon plasticity after optic nerve injury. Of note, the loss of EphB3 did not affect the ability of injured RGC axons to elaborate complex terminal branching, suggesting that additional EphB3-independent mechanisms governed adult axon branching triggered by CNS damage.

According to WHO, pediatric diabetes is a rising global public health problem, with increasing impact on developing nations. This study summarizes a multidimensional, scalable pilot evaluation of a diabetes self-management platform combining mobile technology with social networking to capture four key metrics of Type 1 diabetes self-management, associated social interactions, and gaming features providing targeted feedback to 8 pediatric users. Based on their 2-month interaction with the application, we analyze click-stream data from social interactions, key health metrics, text comments, and usability and satisfaction surveys to evaluate engagement with the platform and effectiveness in controlling blood glucose using a product-process-program framework. Our preliminary results indicate that this framework was successful in demonstrating the potential of the mobile health platform to effectively leverage the growing use of mobile applications and social media to present a unique benefit that engaged pediatric users and provided useful insights for self-health management.

Background and Objectives: To identify the effects of global health electives over a decade in a pediatric residency program. Methods: This was an anonymous email survey of the Boston Combined Residency alumni funded for global health electives from 2002 to 2011. A test for trend in binomial proportions and logistic regression were used to document associations between elective and participant characteristics and the effects of the electives. Qualitative data were also analyzed. Results: Of the 104 alumni with available email addresses, 69 (66%) responded, describing 94 electives. Elective products included 27 curricula developed, 11 conference presentations, and 7 academic publications. Thirty-two (46%) alumni continued global health work. Previous experience, previous travel to the site, number of global electives, and cumulative global elective time were associated with postresidency work in global health or with the underserved. Conclusions: Resident global electives resulted in significant scholarship and teaching and contributed to long-term career trajectories.

e13002Background: Next generation sequencing (NGS) of blood-derived nucleic acids is an emerging paradigm for determining the mutational status of cancer patients over time. Circulating tumor cells...

e16607Background: Next generation sequencing (NGS) of blood-derived nucleic acids is an emerging paradigm for determining the mutational status of cancer patients over time. Circulating tumor cells...

Background Optimal methods for implementing HIV screening in health care settings remain unknown. Objective To compare the acceptance rates of emergency department HIV screening when supplemental staff use opt-in and opt-out consent methods. Methods Experimental equivalent time-sample, conducted in an urban emergency department with an annual census of 80,000 visits. HIV screeners performed nontargeted HIV screening using point-of-care, rapid HIV tests. Eligible patients were medically stable, English or Spanish speaking, ≥13 or ≤64 years, not HIV tested in past 6 months, and not psychiatrically impaired. Screeners offered eligible patients HIV screening using either opt-in or opt-out consent methods on alternate weeks. Main outcome measures were the acceptance rate of HIV screening and the association between opt-out rapid HIV screening and acceptance. Results Of the eligible patients, 2409 were offered HIV screening, with 1209 (50%) on opt-in days and 1200 (50%) on opt-out days. The mean age was 40 years, 52% were male, 45% were Black, 28% Hispanic, and 15% white. The acceptance rate of opt-in HIV screening was 63% [767 of 1209, 95% confidence interval (CI): 61% to 66%] and the acceptance rate of opt-out HIV screening was 78% (931 of 1200, 95% CI: 75% to 80%), absolute difference 14% (95% CI: 11% to 18%). The acceptance rate of opt-out HIV screening remained greater after adjusting for patient demographics, admission status, acuity, treatment area, privacy of encounter, and screening staff identity (adjusted odds ratio: 2.0, 95% CI: 1.7 to 2.4). Conclusions Opt-out HIV screening using supplemental staff increases patient acceptance and should be considered as the consent methodology of choice.

Aortic atheromatous disease is a common finding in the patient presenting for cardiac surgery. Adverse neurologic outcome has been closely linked to the extent of aortic atherosclerosis. In order to optimize perioperative outcomes, the location and severity of disease needs accurate characterization using multimodal techniques. Although various preoperative radiographic techniques have variably identified patients with significant atheroma, intraoperative echocardiographic imaging has proven most useful in localizing and characterizing the degree of aortic atheroma. Epiaortic assessment of the ascending aorta has been utilized in guiding surgical modifications and interventions aimed at reducing the risk of neurologic injury. Although no particular technique has been definitely studied, avoidance of the identifiable atheromatous aortic region has been a main feature of the various modifications employed to optimize neurologic outcome after cardiac surgery.

R1479, a 4'-azidocytidine nucleoside analog, was developed for the treatment of Hepatitis C virus infection. Balapiravir (R1626) is the tri-isobutyrate ester prodrug of R1479 under clinical development to improve exposure of R1479 upon oral administration.The chemical stability and the rate of azide release of R1479 and balapiravir were studied.R1479 and balapiravir solutions were prepared at different pH values and stored at various temperatures. An ion pair high-performance liquid chromatography (HPLC) method with gradient elution was employed to analyze the prodrug, parent, and degradation products. Azide was measured using a reversed phase HPLC method with UV detection after formation of the 3,5-dinitrobenzoyl azide derivative with 3,5-dinitrobenzoyl chloride. The data were analyzed using initial rate and conventional first-order kinetic methods.R1479 degrades to cytosine and azide in aqueous solutions, whereas balapiravir mainly degrades to R1479 and mono- and diesters of R1479. The rates of azide release from R1479 and balapiravir were generally comparable with the corresponding amount formed of cytosine.Azide release is pH dependent and is faster in acidic solutions than in neutral solutions. The amount of azide released is significantly less from balapiravir than that from R1479, suggesting a potential advantage of the prodrug over the parent drug.

To determine the rate of successful conversion of epidural labour analgesia (ELA) to epidural surgical anesthesia (ESA) for intrapartum Cesarean delivery (CD) with identification of potential risk factors for inadequate ESA. Secondary outcomes include a comparison of the management by subspecialist obstetric anesthesiologists (OB) vs. generalist anesthesiologists (GEN), when inadequate ESA was encountered, with an intention of identifying potential interventional strategies to reduce the need for general anesthesia (GA).Health records of all parturients who received ELA and who underwent intrapartum CD during the 3-year period from April 01, 2001 to March 31, 2004 were manually reviewed. Data were analyzed using t test, Chi-square, Fisher's exact test, and analysis of variance where appropriate. A P0.05 was considered significant.Eight hundred ninety-nine cases were identified. Four were excluded, as two received continuous spinal labour analgesia and two underwent emergency CD with insufficient time for conversion to ESA. Initially, 86.6% (775/895) of the 895 cases were successfully converted to ESA leaving 120 cases of inadequate ESA, 36 of these were managed by OB and 84 by GEN. Ineffective ELA was identified as a risk factor for unsuccessful conversion. Pulling the epidural catheter back 1 cm was identified as an effective intervention that resulted in the successful conversion in80% of the 120 cases of inadequate ESA. Spinal anesthesia proved effective in 75% of cases. Both interventions reduced the need for GA to 1.2% for OB and 5.6% for GEN.This investigation provides anesthesiologists with strategies to manage inadequate ESA for intrapartum CD that may reduce the need for GA.

Myocarditis, defined as inflammation of the heart muscle, occurs in response to a wide variety of agents (1). Infectious organisms, a major cause of myocarditis, can have direct cardiomyopathic effects or can predispose to infection with cardiotropic viruses. Viruses can infect cardiac muscle cells or other supporting cells within the heart and cause myocarditis. Coxsackievirus B, adenoviruses, and herpesviruses are important causes of viral myocarditis, especially in North America and Europe (2), and human immunodeficiency virus (HIV) has recently been added to the list of infectious agents that cause myocarditis (3) (Table 1). The overall prevalence of myocarditis in patients with suspected viral illness ranges from 2.3% to 5% (4); however, the incidence of viral myocarditis is difficult to determine because of the limited methods for identifying viral infection of the heart.

This article details a major digitization and access project to make Variety ’s run from 1905 to 1940 freely available online. It uses multiple quantitative research methods—including distant-reading practices of the Digital Humanities and quantitative content analysis—to argue that Variety ’s decisions about when and how to cover the film and radio industries need to be understood as a series of specific internal strategies made in relation to a dynamic business environment. Situating the project’s digitization of Variety as a form of philology, the authors argue that corpus digitization should be considered a scholarly practice, not simply a technical one.

Circulating tumor cells (CTCs) provide a readily accessible source of tumor material from patients with cancer. Molecular profiling of these rare cells can lead to insight on disease progression and therapeutic strategies. A critical need exists to isolate CTCs with sufficient quantity and sample integrity to adapt to conventional analytical techniques. We present a microfluidic platform (IsoFlux) that uses flow control and immunomagnetic capture to enhance CTC isolation. A novel cell retrieval mechanism ensures complete transfer of CTCs into the molecular assay. Improved sensitivity to the capture antigen was demonstrated by spike-in experiments for three cell lines of varying levels of antigen expression. We obtained spike-in recovery rates of 74%, 75%, and 85% for MDA-MB-231 (low), PC3 (middle), and SKBR3 (high) cell lines. Recovery using matched enumeration protocols and matched samples (PC3) yielded 90% and 40% recovery for the IsoFlux and CellSearch systems, respectively. In matched prostate cancer samples (N = 22), patients presenting more than four CTCs per blood draw were 95% and 36% using IsoFlux and CellSearch, respectively. An assay for detecting KRAS mutations was described along with data from patients with colorectal cancer, of which 87% presented CTCs above the assay's limit of detection (four CTCs). The CTC KRAS mutant rate was 50%, with 46% of patients displaying a CTC KRAS mutational status that differed from the previously acquired tissue biopsy data. The microfluidic system and mutation assay presented here provide a complete workflow to track oncogene mutational changes longitudinally with high success rates.

Polyoxometalates (POM) are polymers of transition metal oxides. They are widely used as analytical reagents and reaction catalysts. Some have anti-viral properties and are being investigated as anti-HIV agents. Due to solubility and stability limitations, separation methods for POM are rare in the literatures. This paper presents a HPLC and a CZE method for the analysis of sodium tungstate, its equilibrium products and isopolyanions. The methods are simple and sensitive, and can be used to monitor the purity, stability and solution equilibria of POM.

To identify genes with upregulated expression at the optic nerve head (ONH) that coincides with retinal ganglion cell (RGC) axon loss in glaucomatous DBA/2J mice. To further demonstrate that the proteins encoded by these genes bind to RGC axons and influence fundamental axon physiology.In situ hybridization and cell-type-specific immunolabeling were performed on ONH sections from DBA/2J mice (3 to 11 months old) and C57Bl/6NCrl mice (10 months old). EphB2-Fc and ephrin-B2-Fc chimeric proteins were applied to adult RGC axons in vitro and in vivo at the ONH to demonstrate protein binding on axons. EphB2-Fc or control Fc protein was applied in a bath or locally to axons preloaded with the calcium indicator Fluo-4-AM, and changes in intra-axonal calcium were determined.EphB2 and ephrin-B2 were specifically upregulated at the ONH of DBA/2J mice starting at 9 months of age, but not in age-matched C57Bl/6NCrl mice or in DBA/2J animals that did not have axon loss. EphA4 was also present at the ONH, but no difference in expression was detected between unaffected and affected animals. EphB2 was expressed by F4/80(+), MOMA2(+), ED1(-) macrophage-like cells, ephrin-B2 was expressed by Iba-1(+) microglia and GFAP(+) astrocytes, whereas EphA4 was expressed by GFAP(+) astrocytes. EphB2-Fc and ephrin-B2-Fc protein bound to RGC axons in culture and to ONH RGC axons in vivo. Adult RGC axons in vitro elevated intra-axonal calcium in response to EphB2-Fc but not to control Fc protein.The expression of EphB2 and ephrin-B2 is upregulated at the ONH of glaucomatous DBA/2J mice coinciding with RGC axon loss. The direct binding of EphB2 and ephrin-B2 on adult RGC axons at the ONH and the ability of EphB2 to elevate intra-axonal calcium indicate that these proteins may affect RGC axon physiology in the setting of glaucoma and thus affect the development or progression of the disease.