Multi-measure investigation of the divergence of implicit and explicit consumer evaluations

This research extends findings that implicit and explicit attitudes may diverge to a consumer evaluation task using multiple measures of implicit evaluation: Evaluative Movement Assessment (EMA; Brendl, Markman, & Messner, 2005), and Evaluative Priming (Fazio,Jackson, Dunton, & Williams,1995). These measures were significantly associated with each other for both positive and negative implicit attitudes. Neither measure predicted explicit liking of the product or explicit intention to purchase the product. We believe this to be the first such demonstrated divergence in a naturalistic, unconditioned consumer evaluation context. Implicit activation of the product’s emotional benefit (e.g., “relaxation”), as assessed in a lexical decision task (LDT) was not associated with the EMA or evaluative priming, but was significantly associated with both explicit emotional state (e.g., relaxation) and explicit purchase intention; the latter effect was not mediated by explicit emotion

A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer.

Lessons learnedThe combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored.BackgroundAndrogen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer. Preclinical data have shown that the two pathways compensate for each other when one is inhibited, and combined inhibition of AR and PI3K signaling may be a viable strategy to prevent or overcome castration resistance.MethodsThis phase I study evaluated the safety and tolerability of abiraterone acetate and prednisone combined with BEZ235, a dual PI3K and mTORC1/2 inhibitor, in men with progressive metastatic castration resistant prostate cancer (mCRPC) who have not received prior chemotherapy.ResultsSix patients (n = 6) were treated at the starting dose level of abiraterone acetate 1,000 mg with prednisone 5 mg twice daily and BEZ235 200 mg twice daily in a 3 + 3 dose escalation design. The study was terminated early because three of the six patients (50%) experienced dose-limiting toxicities: grade 3 mucositis, grade 3 hypotension, and grade 4 dyspnea and pneumonitis. All six patients had previously progressed on abiraterone/prednisone. The median treatment duration was 27 days (range: 3-130 days). No prostate-specific antigen (PSA) decline or objective response were observed.ConclusionThe combination of standard-dose abiraterone/prednisone with BEZ235 200 mg twice daily was poorly tolerated in patients with mCRPC. The on-target and off-target effects of dual PI3K and mTORC inhibition likely contributed to the unacceptable toxicity profile. The Oncologist 2017;22:503-e43

A Loophole In Financial Accounting: A Detailed Analysis Of Repo 105

From 2000 to 2008, Lehman used repo transactions to hide billions of dollars on their statements. They alsomisrepresented the repo transactions as secured borrowings even though they actually recorded the transactions as sales. Valukas report in 2010 stimulated an extensive coverage of the repo transactions and spurred an array of studies addressing issues related to the collapse of financial institutions. Since the Repo 105 maneuver of Lehman provides a good example on how regulatory deficiencies can induce companies to obscure financial reporting and the importance of ethics in deterring these abuses, our study intends to examine repo transactions related accounting standards, illustrate how repo transactions can enhance a banks financial statements, and discuss the importance of business ethics in curtailing accounting irregularities

A Case of Burnt-Out Langerhans Cell Histiocytosis Presenting as Postpartum Hypopituitarism

Objective: To evaluate the case of a woman who presented with central hypogonadism and diabetes insipidus and further developed a persistent cough leading to an unexpected diagnosis of burnt-out Langerhans cell histiocytosis (LCH). Methods: Clinical and laboratory endocrine evaluation, magnetic resonance imaging, high-resolution computed tomography, and open-lung biopsy results are discussed. Results: A 28-year-old woman presented at 10 months postpartum with polydipsia, polyuria, and amenorrhea for 3 months. Her results showed a prolactin level of 25 μg/L (reference,<23.5 μg/L), estrogen level of 91 pmol/L (reference, 110-180 pmol/L), follicle-stimulating hormone level of 6 IU/L (reference, 2-20 IU/L), and luteinizing hormone level of 6 IU/L (reference, 2-70 IU/L). A water-deprivation test found a sodium concentration of 148 mmol/L (reference, 135-145 mmol/L), serum osmolality of 310 mmol/kg (reference, 275-295 mmol/kg), and urine osmolality of 107 mmol/kg (reference, 50-1450 mmol/kg) that improved to 142 mEq/L, 295 mmol/kg, and 535 mmol/kg, respectively, after desmopressin administration. Gadolinium-enhanced pituitary magnetic resonance imaging demonstrated a markedly thickened stalk with uniform enhancement. Chest high-resolution computed tomography confirmed bilateral upper-zone cystic lung disease suggestive of either pulmonary lymphangioleiomyomatosis or LCH. Eventual histology showed CD1a-positive burnt-out LCH. This differentiation was crucial as pulmonary lymphangioleiomyomatosis exacerbates with estrogen therapy and pregnancy, which the patient was able to successfully pursue without disease exacerbation. Conclusion: The patient's initial presentation was considered as lymphocytic hypophysitis, but subsequent cystic changes on high-resolution computed tomography led to a unifying definitive diagnosis of burnt-out LCH. This case highlights the importance of investigating for uncommon secondary causes of hypophysitis

Population genetics in microchannels

Spatial constraints such as rigid barriers affect the dynamics of cell populations, potentially altering the course of natural evolution. In this paper, we study the population genetics of Escherichia coli proliferating in microchannels with open ends. Our experiments reveal that competition among two fluorescently labeled E. coli strains growing in a microchannel generates a self-organized stripe pattern aligned with the axial direction of the channel. To account for this observation, we employ a lattice population model in which reproducing cells push entire lanes of cells towards the open ends of the channel. By combining mathematical theory, numerical simulations, and experiments, we find that the fixation dynamics is extremely fast along the axial direction, with a logarithmic dependence on the number of cells per lane. In contrast, competition among lanes is a much slower process. We also demonstrate that random mutations appearing in the middle of the channel and close to its walls are much more likely to reach fixation than mutations occurring elsewhere.Comment: 21 pages, 14 figure

Decoupling social status and status certainty effects on health in macaques: a network approach.

BackgroundAlthough a wealth of literature points to the importance of social factors on health, a detailed understanding of the complex interplay between social and biological systems is lacking. Social status is one aspect of social life that is made up of multiple structural (humans: income, education; animals: mating system, dominance rank) and relational components (perceived social status, dominance interactions). In a nonhuman primate model we use novel network techniques to decouple two components of social status, dominance rank (a commonly used measure of social status in animal models) and dominance certainty (the relative certainty vs. ambiguity of an individual's status), allowing for a more complex examination of how social status impacts health.MethodsBehavioral observations were conducted on three outdoor captive groups of rhesus macaques (N = 252 subjects). Subjects' general physical health (diarrhea) was assessed twice weekly, and blood was drawn once to assess biomarkers of inflammation (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)).ResultsDominance rank alone did not fully account for the complex way that social status exerted its effect on health. Instead, dominance certainty modified the impact of rank on biomarkers of inflammation. Specifically, high-ranked animals with more ambiguous status relationships had higher levels of inflammation than low-ranked animals, whereas little effect of rank was seen for animals with more certain status relationships. The impact of status on physical health was more straightforward: individuals with more ambiguous status relationships had more frequent diarrhea; there was marginal evidence that high-ranked animals had less frequent diarrhea.DiscussionSocial status has a complex and multi-faceted impact on individual health. Our work suggests an important role of uncertainty in one's social status in status-health research. This work also suggests that in order to fully explore the mechanisms for how social life influences health, more complex metrics of social systems and their dynamics are needed

Voltage-gated ion channels mediate the electrotaxis of glioblastoma cells in a hybrid PMMA/PDMS microdevice

Transformed astrocytes in the most aggressive form cause glioblastoma, the most common cancer in the central nervous system with high mortality. The physiological electric field by neuronal local field potentials and tissue polarity may guide the infiltration of glioblastoma cells through the electrotaxis process. However, microenvironments with multiplex gradients are difficult to create. In this work, we have developed a hybrid microfluidic platform to study glioblastoma electrotaxis in controlled microenvironments with high throughput quantitative analysis by machine learning-powered single cell tracking software. By equalizing the hydrostatic pressure difference between inlets and outlets of the microchannel, uniform single cells can be seeded reliably inside the microdevice. The electrotaxis of two glioblastoma models, T98G and U-251MG, requires an optimal laminin-containing extracellular matrix and exhibits opposite directional and electro-alignment tendencies. Calcium signaling is a key contributor in glioblastoma pathophysiology but its role in glioblastoma electrotaxis is still an open question. Anodal T98G electrotaxis and cathodal U-251MG electrotaxis require the presence of extracellular calcium cations. U-251MG electrotaxis is dependent on the P/Q-type voltage-gated calcium channel (VGCC) and T98G is dependent on the R-type VGCC. U-251MG electrotaxis and T98G electrotaxis are also mediated by A-type (rapidly inactivating) voltage-gated potassium channels and acid-sensing sodium channels. The involvement of multiple ion channels suggests that the glioblastoma electrotaxis is complex and patient-specific ion channel expression can be critical to develop personalized therapeutics to fight against cancer metastasis. The hybrid microfluidic design and machine learning-powered single cell analysis provide a simple and flexible platform for quantitative investigation of complicated biological systems

Atypical Chryseobacterium meningosepticum and meningitis and sepsis in newborns and the immunocompromised, Taiwan.

From 1996 to 1999, 17 culture-documented systemic infections due to novel, atypical strains of Chryseobacterium meningosepticum occurred in two newborns and 15 immunocompromised patients in a medical center in Taiwan. All clinical isolates, which were initially misidentified as Aeromonas salmonicida by an automated bacterial identification system, were resistant to a number of antimicrobial agents. The isolates were characterized as atypical strains of C. meningosepticum by complete biochemical investigation, 16S rRNA gene sequence analysis, cellular fatty acid analysis, and random amplified polymorphic DNA fingerprinting (RAPD). This is the first report of a cluster of atypically variant strains of C. meningosepticum, which may be an emerging pathogen in newborns and the immunocompromised

Glioblastoma adhesion in a quick-fit hybrid microdevice

Translational research requires reliable biomedical microdevices (BMMD) to mimic physiological conditions and answer biological questions. In this work, we introduce a reversibly sealed quick-fit hybrid BMMD that is operator-friendly and bubble-free, requires low reagent and cell consumption, enables robust and high throughput performance for biomedical experiments. Specifically, we fabricate a quick-fit poly(methyl methacrylate) and poly(dimethyl siloxane) (PMMA/PDMS) prototype to illustrate its utilities by probing the adhesion of glioblastoma cells (T98G and U251MG) to primary endothelial cells. In static condition, we confirm that angiopoietin-Tie2 signaling increases the adhesion of glioblastoma cells to endothelial cells. Next, to mimic the physiological hemodynamic flow and investigate the effect of physiological electric field, the endothelial cells are pre-conditioned with concurrent shear flow (with fixed 1 Pa shear stress) and direct current electric field (dcEF) in the quick-fit PMMA/PDMS BMMD. With shear flow alone, endothelial cells exhibit classical parallel alignment; while under a concurrent dcEF, the cells align perpendicularly to the electric current when the dcEF is greater than 154 V m(-1). Moreover, with fixed shear stress of 1 Pa, T98G glioblastoma cells demonstrate increased adhesion to endothelial cells conditioned in dcEF of 154 V m(-1), while U251MG glioblastoma cells show no difference. The quick-fit hybrid BMMD provides a simple and flexible platform to create multiplex systems, making it possible to investigate complicated biological conditions for translational research

Community and service provider views to inform the 2013 WHO consolidated antiretroviral guidelines:key findings and lessons learnt

Objective:The objective was to evaluate community and healthcare worker (HCW) values and preferences on key topics to inform the development of the 2013 WHO consolidated guidelines for antiretroviral therapy in low and middle income countries. Design:Cross-sectional e-survey and e-forum discussion; focus group discussions (FGDs) Methods:Data were collected on community perspectives regarding a range of potential clinical and operational recommendations in the 2013 guidelines between November 2012 and January 2013 through an e-survey (n = 1088) and e-forum (n = 955). Additional FGDs were held with people living with HIV (PLHIV) in Malawi and Uganda (n = 88) on antiretroviral therapy (ART) use among pregnant women. Two surveys were also undertaken on similar topics covered in the e-survey for health care workers caring for adults (n = 98) and children (n = 348). Results:There were 1088 e-survey respondents from 117 countries: of whom 37.7% (298/791) were females, 49.9% (431/864) PLHIV, and 20.9% (174/831) from low-income countries. The proportion of e-survey respondents who supported raising the CD4 T-cell threshold for ART initiation in adults from 350 to 500 cells/μl was 51.0% (355/696), and regardless of CD4 T-cell count for all pregnant females 89.8% (607/676), HIV serodiscordant partners 71.9% (486/676), and all children on diagnosis of infection 47.4% (212/447). E-survey respondents strongly supported discontinuing use of stavudine (72.7%, 416/572), task-shifting/sharing from doctors to nurses (75.2%, 275/365) and from nurses to community health workers (71.1%, 261/367) as strategies to expand access to HIV testing, care, and treatment. Focus group discussion respondents identified service capacity, and social and legal concerns as key considerations influencing the decisions of women living with HIV to continue ART after the risk of vertical transmission has passed. Key lessons learnt in these consultations included the need for piloting and validation of questions; sufficient time to adequately disseminate the survey; and consideration of using FGDs and mobile phone technology to improve participation of people with limited internet access. Conclusion:Community participation in guideline development processes is important to ensure that their perspectives are considered in the resulting recommendations. Communities should be actively involved in the adaptation, implementation, and accountability processes related to the guidelines