EXPRESS: Learning from Data: An Empirics-First Approach to Relevant Knowledge Generation

A “theory-first” paradigm tends to be the dominant approach in much academic marketing research. In this approach, a theory is borrowed, refined, or developed and then tested empirically. In this challenging-the-boundaries article, we make a case for an “empirics-first” approach. Empirics-first refers to research that (i) is grounded in (originates from) a real-world marketing phenomenon, problem, or observation, (ii) involves obtaining and analyzing data, and (iii) produces valid marketing-relevant insights without necessarily developing or testing theory. The empirics-first approach is not antagonistic to theory but rather can serve as a stepping-stone to theory. The approach lends itself well to today’s data-rich environment, which can surface novel research questions untethered to theory. The present paper describes the underlying principles of an empirics-first approach, which consists of exploring a domain purposefully without preconceptions. Using a rich set of published examples, the present paper offers guidance on how to implement empirics-first research and how it can lead to valuable knowledge development. Advice is also offered to authors on how to report EF research and to reviewers and to editorial teams on how to evaluate it. Our ultimate objective is to pave a way for empirics-first to enter the mainstream of academic marketing research

BRCA1 intronic Alu elements drive gene rearrangements and PARP inhibitor resistance

Resistència terapèutica contra el càncer; Càncer d'ovarisResistencia terapéutica al cáncer; Cáncer de ovariosCancer therapeutic resistance; Ovarian cancerBRCA1 mutant carcinomas are sensitive to PARP inhibitor (PARPi) therapy; however, resistance arises. BRCA1 BRCT domain mutant proteins do not fold correctly and are subject to proteasomal degradation, resulting in PARPi sensitivity. In this study, we show that cell lines and patient-derived tumors, with highly disruptive BRCT domain mutations, have readily detectable BRCA1 protein expression, and are able to proliferate in the presence of PARPi. Peptide analyses reveal that chemo-resistant cancers contain residues encoded by BRCA1 intron 15. Mechanistically, cancers with BRCT domain mutations harbor BRCA1 gene breakpoints within or adjacent to Alu elements in intron 15; producing partial gene duplications, inversions and translocations, and terminating transcription prior to the mutation-containing BRCT domain. BRCA1 BRCT domain-deficient protein isoforms avoid mutation-induced proteasomal degradation, support homology-dependent DNA repair, and promote PARPi resistance. Taken together, Alu-mediated BRCA1 gene rearrangements are responsible for generating hypomorphic proteins, and may represent a biomarker of PARPi resistance.This work was supported by the US National Institutes of Health (NIH) Grants P50 CA083638 and 5P30 CA006927, as well as R01CA214799, Susan Komen CCRCR17499048, and OC130212 Department of Defense to N.J., and a Pilot Award and Nested Teal Postdoctoral Scholar supported Y.W. (OC140040). We thank Drs. Judith Balmaña, Cristina Saura and Joaquin Arribas for providing materials. PDXs were established thanks to the GHD-Pink program, the FERO Foundation and the Catalan Agency AGAUR [2017 SGR 540]. V.S. is supported by the Instituto de Salud Carlos III (CP14/00228) and ALG by a PERIS fellowship from the Departament de Salut, Generalitat de Catalunya (SLT002/16/00477). Clovis Oncology supplied rucaparib. We are grateful to FCCC Genomics, Cell Culture and Cell Sorting facilities. We thank Hsin Yao Tang at the Wistar Proteomics facility for help with mass spectrometry

Non-Conscious Influences on Consumer Choice

While consumer choice research has dedicated considerable research attention to aspects of choice that are deliberative and conscious, only limited attention has been paid to aspects of choice that occur outside of conscious awareness. We review relevant research that suggests that consumer choice is a mix of conscious and nonconscious influences, and argue that the degree to which nonconscious influences affect choice is much greater than many choice researchers believe. Across a series of research domains, these influences are found to include stimulus that are not consciously perceived by the consumer, nonconscious downstream effects of a consciously perceived stimuli or thought process, and decision processes that occur entirely outside of awareness

Changing plasma cytokine, chemokine and growth factor profiles upon differing malaria transmission intensities

Background: Malaria epidemiological and immunological data suggest that parasite tolerance wanes in the absence of continuous exposure to the parasite, potentially enhancing pathogenesis. The expansion of control interventions and elimination campaigns raises the necessity to better understand the host factors leading to susceptibility or tolerance that are afected by rapid changes in malaria transmission intensity (MTI). Mediators of cellular immune responses are responsible for the symptoms and pathological alterations during disease and are expected to change rapidly upon malaria exposure or cessation. Methods: The plasma concentrations of 30 cytokine, chemokine and growth factors in individuals of all ages from a malaria endemic area of southern Mozambique were compared between 2 years of diferent MTI: 2010 (lower, n=234) and 2013 (higher, n=143). The efect of the year on the correlations between cytokines, chemokines and growth factors and IgGs to Plasmodium falciparum (markers of exposure) was explored. The efects of age, sex, neighbourhood and parasitaemia on analyte levels and their interactions with year were also assessed. Results: An inverse correlation of several cellular immune mediators with malarial antibodies in 2013, and a lack of correlation or even a positive correlation in 2010 were observed. Most cytokines, chemokines and growth factors, regardless of their immune function, had higher concentrations in 2010 compared with 2013 in P. falciparum-infected and uninfected subjects. Age and neighbourhood showed an efect on analyte concentrations. Conclusions: The results show a diferent regulation of the cellular immune response in 2010 vs 2013 which could be related to a loss of immune-tolerance after a decline in MTI in 2010 and previous years, and a rapid re-establishment of tolerance as a consequence of more continuous exposure as MTI began increasing in 2012. Cellular immune mediators warrant further investigation as possible surrogates of MTI-associated host susceptibility or tolerance

Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling indoor- and outdoor-resting mosquitoes in southern Tanzania.

BACKGROUND\ud \ud Resting mosquitoes can easily be collected using an aspirating device. The most commonly used mechanical aspirator is the CDC Backpack aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has been devised and proved to have comparable performance. The following study evaluates the Prokopack aspirator compared to the CDC backpack aspirator when sampling resting mosquitoes in rural Tanzania.\ud \ud METHODS\ud \ud Mosquitoes were sampled in- and outdoors of 48 typical rural African households using both aspirators. The aspirators were rotated between collectors and households in a randomized, Latin Square design. Outdoor collections were performed using artificial resting places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof and from a drop-net. Data were analysed with generalized linear models.\ud \ud RESULTS\ud \ud The number of mosquitoes collected using the CDC Backpack and the Prokopack aspirator were not significantly different both in- and outdoors (indoors p = 0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The Prokopack was superior for sampling of drop-nets due to its smaller size. The number mosquitoes collected per technician was more consistent when using the Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred using the it over the CDC backpack aspirator as it weighs considerably less, retains its charge for longer and is easier to manoeuvre.\ud \ud CONCLUSIONS\ud \ud The Prokopack proved in the field to be more advantageous than the CDC Backpack aspirator. It can be self assembled using simple, low-cost and easily attainable materials. This device is a useful tool for researchers or vector-control surveillance programs operating in rural Africa, as it is far simpler and quicker than traditional means of sampling resting mosquitoes. Further longitudinal evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray catch for indoor resting catches are recommended

Calibration and Characterization of the IceCube Photomultiplier Tube

Over 5,000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-inch diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts.Comment: 40 pages, 12 figure

Improved molecular laboratory productivity by consolidation of testing on the new random-access analyzer Alinity m

Abstract Objectives Automated molecular analyzers have accelerated diagnosis, allowing earlier intervention and better patient follow-up. A recently developed completely automated molecular analyzer, Alinity™ m (Abbott), offers consolidated, continuous, and random-access testing that may improve molecular laboratory workflow. Methods An international, multicenter study compared laboratory workflow metrics across various routine analyzers and Alinity m utilizing assays for human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV), high-risk human papillomavirus (HR HPV), and sexually transmitted infection (STI) (Chlamydia trachomatis [CT]/Neisseria gonorrhoeae [NG]/Trichomonas vaginalis [TV]/Mycoplasma genitalium [MG]). Three turnaround times (TATs) were assessed: total TAT (sample arrival to result), sample onboard TAT (sample loading and test starting to result), and processing TAT (sample aspiration to result). Results Total TAT was reduced from days with routine analyzers to hours with Alinity m, independent of requested assays. Sample onboard TATs for standard workflow using routine analyzers ranged from 7 to 32.5 h compared to 2.75–6 h for Alinity m. The mean sample onboard TAT for STAT samples on Alinity m was 2.36 h (±0.19 h). Processing TATs for Alinity m were independent of the combination of assays, with 100% of results reported within 117 min. Conclusions The consolidated, continuous, random-access workflow of Alinity m reduces TATs across various assays and is expected to improve both laboratory operational efficiency and patient care

Multicenter clinical comparative evaluation of Alinity m HIV-1 assay performance.

Abstract Background Accurate, rapid detection of HIV-1 RNA is critical for early diagnosis, treatment decision making, and long-term management of HIV-1 infection. Objective We evaluated the diagnostic performance of the Alinity m HIV-1 assay, which uses a dual target/dual probe design against highly conserved target regions of the HIV-1 genome and is run on the fully automated Alinity m platform. Study design This was an international, multisite study that compared the diagnostic performance of the Alinity m HIV-1 assay to four commercially available HIV-1 assays routinely used in nine independent clinical laboratories. Alinity m HIV-1 assay precision, detectability, and reproducibility was compared across four study sites. Results The Alinity m HIV-1 assay produced comparable results to currently available HIV-1 assays (correlation coefficient >0.995), with an overall bias of -0.1 to 0.10 Log10 copies/mL. The Alinity m HIV-1 assay and its predecessor m2000 HIV-1 assay demonstrated comparable detection of 16 different HIV-1 subtypes (R2 = 0.956). A high level of agreement (>88 %) between all HIV-1 assays was seen near clinical decision points of 1.7 Log10 copies/mL (50 copies/mL) and 2.0 Log10 copies/mL (200 copies/mL). Alinity m HIV-1 assay precision was 0.08 and 0.21 Log10 copies/mL at VLs of 1000 and 50 copies/mL, respectively, with a high level of detectability (≥97 % hit rate) and reproducibility across sites. Conclusions The Alinity m HIV-1 assay provides comparable diagnostic accuracy to current HIV-1 assays, and when run on the Alinity m system, has the capacity to shorten the time between diagnosis and treatment

Aspects of superconformal multiplets in D > 4

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