A Probabilistic Study Of Safety Criteria For Design

National Science Foundation Under Grant GK-1812

A Study Of Travel Agency Collaboration And Co-Creation In The Tourism Industry

This study explores the dynamics of collaboration between travel agencies and their suppliers in co-creating value with their customers. It examines the relationship among six collaboration elements (co-creation dynamics), service innovation, competitive advantage, technology adoption and environmental change, and the moderating effect of trust on the co-creation elements and service innovation. The effects of technology adoption and environmental changes on the six elements were also examined. Results indicate that all the above effects are significant, and trust enhances the effect of the elements on innovation for Taiwan travel agencies. However, technology adoption and trust differed for the Malaysian travel agencies

Prevalence of established and emerging biomarkers of immune checkpoint inhibitor response in advanced hepatocellular carcinoma.

The clinical deployment of immune checkpoint inhibitors (ICIs) has created a tandem drive for the identification of biomarkers linked to benefit. Comprehensive genomic profiling was performed to evaluate the frequency of genomic biomarkers of ICI response in 755 patients with advanced hepatocellular carcinoma (HCC). Median age was 62 years' old, 73% were male, 46% had extrahepatic disease, 107 had documented hepatitis C, 96 had hepatitis B and 4 patients were coinfected. Median tumor mutation burden (TMB) was 4 mutations/Mb and only 6 tumors (0.8%) were TMB-high. Out of 542 cases assessed for microsatellite instability (MSI), one (0.2%) was MSI-high and TMB-high. Twenty-seven (4%) patients had POLE/D alterations. One patient had a pathogenic POLE R762W mutation but TMB was 4 mutations/Mb. Forty percent had DNA damage response gene alterations. In a small case series (N=17) exploring the relationship between biomarkers and ICI response, one patient (TMB 15 mutations/Mb, MSI-low) had a sustained complete response to nivolumab lasting > 2 years. Otherwise there were no significant genomic or TMB differences between responders, progressors, and those with stable disease. Overall, markers of genomic instability were infrequent in this cohort. Larger clinically annotated datasets are needed to explore genomic and non-genomic determinants of ICI response in HCC

High density of ‘spiky’ excrescences covering the surface of an erythrocyte infected with Plasmodium malariae

10.1111/j.1365-2141.2010.08261.xBritish Journal of Haematology15111-BJHE

Performance and Performance Persistence of Socially Responsible Investment Funds in Europe and North America

We analyze, and compare, performance and performance persistence of Socially Responsible Investment (SRI) funds in Europe and North America. We use a broad sample of 500 European and 248 North American SRI funds for the period January 2001 - December 2011. We find that SRI funds outperform the market benchmark in Europe and North America over this period and that North American SRI funds perform better than European SRI funds. We find little evidence of performance persistence in either region using a ranked portfolio approach; however, there is more evidence of performance persistence in European SRI funds than in their North American counterparts using a non-parametric ranked portfolio approach

Performance and Performance Persistence of Socially Responsible Investment Funds in Europe and North America

We analyze, and compare, performance and performance persistence of Socially Responsible Investment (SRI) funds in Europe and North America. We use a broad sample of 500 European and 248 North American SRI funds for the period January 2001 - December 2011. We find that SRI funds outperform the market benchmark in Europe and North America over this period and that North American SRI funds perform better than European SRI funds. We find little evidence of performance persistence in either region using a ranked portfolio approach; however, there is more evidence of performance persistence in European SRI funds than in their North American counterparts using a non-parametric ranked portfolio approach

An Effective Meaningful Way to Evaluate Survival Models

One straightforward metric to evaluate a survival prediction model is based on the Mean Absolute Error (MAE) -- the average of the absolute difference between the time predicted by the model and the true event time, over all subjects. Unfortunately, this is challenging because, in practice, the test set includes (right) censored individuals, meaning we do not know when a censored individual actually experienced the event. In this paper, we explore various metrics to estimate MAE for survival datasets that include (many) censored individuals. Moreover, we introduce a novel and effective approach for generating realistic semi-synthetic survival datasets to facilitate the evaluation of metrics. Our findings, based on the analysis of the semi-synthetic datasets, reveal that our proposed metric (MAE using pseudo-observations) is able to rank models accurately based on their performance, and often closely matches the true MAE -- in particular, is better than several alternative methods.Comment: Accepted to ICML 202

Saying goodbye to Friends: Situation comedy as lived experience

The series finale for NBC’s sitcom Friends was a media event, a two-hour broadcast promoted for months, and immediately followed by cast appearances on late night comedy shows and the next morning’s news shows. The show’s popularity demonstrated by fan response to the last episode positions the online and broadcast media discourse surrounding the finale as a rich cultural text for examining the influence of the modern sitcom on fans’ cultural identities and social communities. The Friends broadcast finale taken together with the online discussion of the show creates a site for the production and consumption of fan culture in three ways. First, the self-referential series finale was a significant media event, which framed the finale as part of fans’ real life experience. Second, fan accoutrement articulates a sense of place that is not just projected into viewers’ living rooms, but into their broader lives. Third, the show’s fictional characters, are portrayed as real friends, and become important personae in fans’ social discourse. The Friends finale is fan text, one that conflates the distinction between real life and the small screen in ways that have implications for broader television criticism

Tiered sympathetic control of cardiac function revealed by viral tracing and single cell transcriptome profiling.

The cell bodies of postganglionic sympathetic neurons innervating the heart primarily reside in the stellate ganglion (SG), alongside neurons innervating other organs and tissues. Whether cardiac-innervating stellate ganglionic neurons (SGNs) exhibit diversity and distinction from those innervating other tissues is not known. To identify and resolve the transcriptomic profiles of SGNs innervating the heart, we leveraged retrograde tracing techniques using adeno-associated virus (AAV) expressing fluorescent proteins (GFP or Td-tomato) with single cell RNA sequencing. We investigated electrophysiologic, morphologic, and physiologic roles for subsets of cardiac-specific neurons and found that three of five adrenergic SGN subtypes innervate the heart. These three subtypes stratify into two subpopulations; high (NA1a) and low (NA1b and NA1c) neuropeptide-Y (NPY) -expressing cells, exhibit distinct morphological, neurochemical, and electrophysiologic characteristics. In physiologic studies in transgenic mouse models modulating NPY signaling, we identified differential control of cardiac responses by these two subpopulations to high and low stress states. These findings provide novel insights into the unique properties of neurons responsible for cardiac sympathetic regulation, with implications for novel strategies to target specific neuronal subtypes for sympathetic blockade in cardiac disease

Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues

Dysfunction of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 subunit and deficits in synaptic plasticity are implicated in schizophrenia and sleep and circadian rhythm disruption. To investigate the role of GluA1 in circadian and sleep behaviour, we used wheel-running, passive-infrared, and video-based home-cage activity monitoring to assess daily rest–activity profiles of GluA1-knockout mice (Gria1−/−). We showed that these mice displayed various circadian abnormalities, including misaligned, fragmented, and more variable rest–activity patterns. In addition, they showed heightened, but transient, behavioural arousal to light→dark and dark→light transitions, as well as attenuated nocturnal-light-induced activity suppression (negative masking). In the hypothalamic suprachiasmatic nuclei (SCN), nocturnal-light-induced cFos signals (a molecular marker of neuronal activity in the preceding ~1–2 h) were attenuated, indicating reduced light sensitivity in the SCN. However, there was no change in the neuroanatomical distribution of expression levels of two neuropeptides―vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP)―differentially expressed in the core (ventromedial) vs. shell (dorsolateral) SCN subregions and both are known to be important for neuronal synchronisation within the SCN and circadian rhythmicity. In the motor cortex (area M1/M2), there was increased inter-individual variability in cFos levels during the evening period, mirroring the increased inter-individual variability in locomotor activity under nocturnal light. Finally, in the spontaneous odour recognition task GluA1 knockouts’ short-term memory was impaired due to enhanced attention to the recently encountered familiar odour. These abnormalities due to altered AMPA-receptor-mediated signalling resemble and may contribute to sleep and circadian rhythm disruption and attentional deficits in different modalities in schizophrenia