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Managerial responses to online customer reviews not only affect customers who receive the responses but may also influence subsequent customers who observe the responses. This externality arises because of the public nature of online interactions. However, prior studies were mainly in offline settings where such externality rarely exists. In this study, we assess the magnitude of such externality. Using a difference-in-difference-in-differences framework and matched hotels across two large travel agencies, we find that managerial responses indeed have a significant and positive impact on the volume of subsequent customer reviews. The impact on the review valence is not evident, which can be attributed to the unique design of identity disclosure in our research context. Furthermore, our results suggest nuances that were not known in the prior literature. For example, responding to positive and negative reviews may have different effects on future reviews, and managers should provide detailed responses to negative reviews but brief ones to positive reviews. Our results offer managerial implications to service providers on how to improve customer engagement in the interconnected online environment. The online appendix is available at https://doi.org/10.1287/isre.2018.0781 .

In this study, we examine whether and how CEO tenure affects firms' corporate social responsibility (CSR) performance. Using a sample of U.S. firms for the 1999–2013 period, we find that firms' CSR performance is significantly higher in CEOs' early tenure than in their later tenure. We also find that the relationship between CEO tenure and CSR performance is stronger when the board is more independent and CEOs have a longer expected employment period, supporting both the signaling interpretation of the career concern hypothesis and the career horizon hypothesis. Consistent with the trend of increasing awareness of the importance of CSR, we find that the relationship between CEO tenure and CSR performance has become more significant in recent years. Finally, we show that better CSR performance in a CEO's early tenure is associated with a lower CEO turnover probability, suggesting that commitment to CSR during CEOs' early tenure could enable them to mitigate career concerns.

SUMMARY High-throughput physiological assays lose single-cell resolution, precluding subtype-specific analyses of activation mechanism and drug effects. We demonstrate APPOINT (automated physiological phenotyping of individual neuronal types), a physiological assay platform combining calcium imaging, robotic liquid handling, and automated analysis to generate physiological activation profiles of single neurons at large scale. Using unbiased techniques, we quantify responses to sequential stimuli, enabling subgroup identification by physiology and probing of distinct mechanisms of neuronal activation within subgroups. Using APPOINT, we quantify primary sensory neuron activation by metabotropic receptor agonists and identify potential contributors to pain signaling. We expand the role of neuroimmune interactions by showing that human serum directly activates sensory neurons, elucidating a new potential pain mechanism. Finally, we apply APPOINT to develop a high-throughput, all-optical approach for quantification of activation threshold and pharmacologically validate contributions of ion channel families to optical activation., In brief DuBreuil et al. demonstrate an integrated platform for high-throughput analysis of calcium responses elicited in individual neurons by sequential stimuli. The automated pipeline leverages machine learning classifiers and will facilitate large-scale studies, including phenotyping of neuronal subtypes, evaluating drug effects within subtypes, and quantifying drug-induced changes in optogenetic rheobase., Graphical Abstract

Background Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is a locally aggressive T-cell lymphoma that can develop following breast implantation. In 2017, and updated in 2019, the National Comprehensive Cancer Network (NCCN) recommended total capsulectomy with implant removal as definitive therapy. Objectives The aim of this study was to evaluate the US insurance coverage for the management of BIA-ALCL and compare it to the NCCN recommendations. Methods A cross-sectional analysis of US insurance policies for coverage of BIA-ALCL treatment was conducted. Insurance companies were selected based on their market share and state enrollment. Medical necessity criteria were abstracted from the publicly available policies. Results Of the 101 companies assessed, only 30 (30%) had a policy for the management of BIA-ALCL. Of those policies, all (n = 30, 100%) provided coverage of the implant removal of the breast diagnosed with BIA-ALCL. For the contralateral breast implant, 20 policies (67%) covered their removal, but significantly fewer did so if the implant was placed for cosmetic reasons vs medically necessary (n = 13 vs n = 20, 43% vs 67%; P = 0.0026). Twenty-one policies (70%) covered an implant reinsertion, but fewer would do so if the implant was cosmetic rather than medically necessary (n = 5, 17% vs 70%; P < 0.0001). Conclusions There was notable intercompany variation in the coverage of BIA-ALCL treatment, some of which is unnecessarily based on whether the original reason for the breast implant was cosmetic or medically necessary. This variability may significantly reduce access to definitive treatment in patients with a BIA-ALCL diagnosis.

SARS-CoV-2 causes severe respiratory infections in some patients due to an uncontrolled immune response. The nasal microenvironment plays a crucial role in the transmission, modulation, and clinical progression of COVID-19, however, the immune-responses at the site of viral entry remain poorly understood. We used flow cytometry to decipher nasopharyngeal immune profiling of COVID-19 positive/negative patients; viral detection and load were performed by RT-PCR. Analysis of viral-induced immune-inflammatory responses, lymphocytes population/activation lymphocytes markers, T cell subtypes and associated inflammatory cytokines. Furthermore, we performed in vitro assays using cultured monocytes-derived-macrophages trained with/without SARS-CoV-2 spike protein and co-cultured with/without autologous T cells. Results showed that positive patients had high inflammatory CD45+ and CD8+ T cells including elevated % of Th1/Th17.1, associated with a worse outcome in a subgroup of COVID-19 infected patients. Positive patients showed increased % of cytokines, IFN-γ+, IL-17+, and IL-10+ T cells suggesting a crucial role of these cytokines in recruiting and activating neutrophils that can migrate to target organs (e.g., lungs) and potentially play an important role in the disease severity. Moreover, upregulated Tregs along with monocytic-induced inflammatory T-cell responses and increased TH1/TH17 cytokines in positive patients as compared to negative, potentially having a nefarious effect on disease progression. Our findings indicate a distinct signature of inflammatory lymphocytes/cytokines responses within the nasopharynx of COVID-19 patients that might predict the clinical outcome/progression of the disease. This work is supported by Dr. Mohamad Ayass, CEO of Ayass Bioscience, LLC

Bipolar disorder is often comorbid with anxiety, which is itself associated with poorer clinical outcomes, including suicide. A better etiologic understanding of this comorbidity could inform diagnosis and treatment. The present study aims to test whether comorbid anxiety in bipolar disorder reflects shared genetic risk factors. We also sought to assess the contribution of genetic risk for anxiety to suicide attempts in bipolar disorder. Polygenic risk scores (PRS) were calculated from published genome-wide association studies of samples of controls and cases with anxiety (n = 83,566) or bipolar disorder (n = 51,710), then scored in independent target samples (total n = 3369) of individuals with bipolar disorder who reported or denied lifetime anxiety disorders or suicidal attempts in research interviews. Participants were recruited from clinical and nonclinical settings and genotyped for common genetic variants. The results show that polygenic risk for anxiety was associated with comorbid anxiety disorders and suicide attempts in bipolar disorder, while polygenic risk for bipolar disorder was not associated with any of these variables. Our findings point out that comorbid anxiety disorders in bipolar disorder reflect a dual burden of bipolar and anxiety-related genes; the latter may also contribute to suicide attempts. Clinical care that recognizes and addresses this dual burden may help improve outcomes in people living with comorbid bipolar and anxiety disorders.

Background The presence of antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and both anti-CCP antibody and RF positivity indicate more severe disease. This characteristic makes Anti-CCP best biomarker candidate for the prevention of debilitating joint disease. Almost 70% of RA patients are positive for anti-CCP IgG, while only 2% of control subjects are positive for anti-CCP. Understanding the origins of anti-CCP is critical in unraveling the etiology of RA, so we further evaluated the association of the other autoimmune tests/biomarkers with Anti-CCP to describe other comorbid autoimmune diseases/syndrome. Methods We conducted a retrospective analysis of patient data from April 18, 2016, to May 29, 2019, in Texas. The study protocol was approved by the ethics review committee and patients consented for sharing their demographics, clinical information and lab values for diagnostic and research purposes. The study population was described by descriptive statistics. Demographic characteristics and laboratory parameters were compared using chi-square tests. We analyzed blood tests/parameters conducted at the clinics and explored their association with the presence of ACCP. logistic regression models were utilized to calculate the odds ratio to delineate the strength of association of different blood parameters with ACCP. IgG anti-CCP was determined according to the manufacturer’s instruction. Results Eleven thousand, four hundred fifty-nine tests were performed on 7,200 patients with a mean age of 52 years (range 0-98). Almost half (54%) of study individuals were females, two-third (63%) were White, (29%) Hispanic and (7%) African American. Four hundred and six patients (3.5%) were positive for AntiCCP3.1. Among those who were positive for AntiCCP3.1, (22%) were Rh factor IgA (RhIgA) positive, (11%) RhIgG positive, and (9%) RhIgM. Univariate logistic regression showed that the female gender was positively associated (OR = 3.19) with ACCP presence while patients older than 50 had a positive gradient of ACCP positivity with each age category. Compared to White, African Americans were more likely (OR = 3.19) and Hispanics were less likely (OR = 0.44) to be associated with AntiCCP positivity. After controlling for age, gender and ethnicity the presence of RhIgM and RhIgA antibodies were positively associated with positive ACCP. (OR = 13.3, OR = 5.2). antiphosphatidylserine IgM and anticardiolipin IgM antibodies were positively associated with ACCP (OR = 2.1, OR = 3.4). Similarly, the presence of antimitochondrial M2 antibodies and anti-topoisomerase antibodies (SCL-70) were very significantly associated with ACCP (OR = 16.1, OR = 37.8). Conclusion The Anti-CCP antibodies are highly specific for the early diagnosis of RA and with early initiation of treatment, progression to irreversible and destructive diseases can be prevented. Association of Anti-CCP antibodies with other autoimmune antibodies highlights the importance of screening RA patients for primary biliary sclerosis and scleroderma. Similarly, a biomarker's strength of interaction with another biomarker helps in the prognostic utility of these test for preventing co-existing diseases. Disclosures M. Ayass: Other; Physician at Ayass Bioscience. K. Zhu: Other; Employee at Ayass Bioscience. S. Naveed: None. L. Mosleh: Other; Employee at Ayass Bioscience. K. Viswanathan: Other; Employee at Ayass Bioscience. G. Nowshad: Other; Employee at Ayass Bioscience.

Human mitochondrial DNA provides a promising target for fecal source tracking because it is unique and intrinsic to humans. We developed a TaqMan chemistry assay, hCYTB484, targeting the cytochrome b gene of the human mitochondrial genome on a droplet digital PCR (ddPCR) platform and compared the performance of hCYTB484 with the HF183/BacR287 assay, a widely used assay targeting human-associated Bacteroides. For both assays, we defined the analytical limit of detection and analytical lower limit of quantification using frequency of detection and imprecision goals, respectively. We then established these analytical limits using empirical ddPCR data, presenting a novel approach to determining the analytical lower limit of quantification. We evaluated assay sensitivity using individual human feces from US, Bangladesh, and Mozambique and evaluated assay specificity using cow, pig, chicken, and goat samples collected from the US. To compare assay performance across a range of thresholds, we utilized receiver operating characteristic curves. The hCYTB484 marker was detected and quantifiable in 100% of the human feces from the 3 geographical distant regions whereas the HF183/BacR287 marker was detectable and quantifiable in 51% and 31% (respectively) of human feces samples. The hCYTB484 marker also was more specific (97%), having fewer detections in pig, chicken, and goat samples than the HF183/BacR287 marker (80%). The higher performance of the hCYTB484 marker in individual feces from geographically distant regions is desirable in the detection of fecal pollution from sources to which fewer individuals contribute, such as the non-sewered forms of sanitation (e.g. pit latrines and septic tanks) that serve most of Earth’s population and carry the highest risk of exposure to fecal-oral pathogens., Graphical abstract Image 1, Highlights • We developed a novel TaqMan chemistry assay for the ddPCR platform targeting human mtDNA. • mtDNA was detected and quantifiable in 100% of human feces samples from the US, Mozambique, and Bangladesh. • mtDNA can complement fecal source tracking methods.

A scale-up nanoporous membrane centrifuge is designed and modeled. It can be used for nanoscale scale separation including reverse osmosis desalination. There are micron-size pores on the wall of the centrifuge and nanoscale pores on local graphene membrane patches that cover the micron-size pores. In this work, we derived the critical angular velocity required to counter-balance osmosis force, so that the reverse-osmosis (RO) desalination process can proceed. To validate this result, we conducted a large scale (four million atoms) full atom molecular dynamics (MD) simulation to examine the critical angular velocity required for reverse osmosis at nanoscale. It is shown that the analytical results derived based on fluid mechanics and the simulation results observed in MD simulation are consistent and well matched. The main advantage of such nanomaterial based centrifuge is its intrinsic anti-fouling ability to clear [Formula: see text] and [Formula: see text] ions accumulated at the vicinity of the pores due to the Coriolis effect. Analyses have been conducted to study the relation between osmotic pressure, centrifugal pressure, and water permeability.

Corruption as a non-market strategy for firms has gained increasing attention in the field of strategy management. However, the effect of corruption on innovation is unclear, especially in the context of transition economies. Using institutional theory, we examine the relationship between corruption and new product innovation and identify the contextual conditions of the relationship. Using the World Bank Enterprise Survey data from China, our empirical results show that corruption has a positive effect on firms’ new product innovation. Moreover, we find that policy instability and competitive threats from the informal sector positively moderate the relationship between corruption and new product innovation. Using post hoc analysis, we find that the potentially positive effect of corruption on new product innovation is the consequence of inherent institutional weaknesses in transition economies; as the level of institutional development increases, the effect of corruption on firms’ new product innovation will gradually decrease. Overall, our findings provide new insights into understanding corrupt behaviors in transition economies and present managerial implications for firms’ ethical dilemmas in a transition economy context. We argue that the key to overcoming these ethical dilemmas lies in promoting pro-market institutional reform to reduce the potential benefits of corruption.

We study the impact of customer information portability on market competition in customer†centric, technology†intensive service industries. By allowing customer information to be transferrable among service providers, portability in theory may help reduce switching costs and promote competition. Yet the actual consequences are unclear. To investigate this issue, we focus on the global wireless industry, and examine the impact of mobile number portability (MNP) policy. We construct a duopoly model with heterogeneous switching costs, which predicts that the market share of the large firm will shrink after MNP, while the average price may depend on firms’ customer base composition. We test these hypotheses empirically on a panel dataset of 218 wireless operators in 52 countries over 6 years. We find relative market share gains for small firms and reductions for large firms under MNP. However, large firms can maintain higher prices than small firms. Probing deeper into customer segmentation, we find that on average, the share of contract customers increases for large firms after MNP, while it decreases for small firms. Large firms are able to retain higher†value contract customers while small firms tend to attract lower†value “pay†as†you†go†customers. Contrary to the policy intention, large firms tend to remain dominant, and MNP is incapable of changing this. In fact, contracts become even more important after MNP, highlighting the sticky “lock†in†effect of contracts. Our findings have broad applicability to other service industries (e.g., healthcare, financial services, and digital media), where policymakers are considering making customer information more portable in hopes of increasing competition.

User contribution is critical to online communities but also difficult to sustain given its public goods nature. This paper studies the design of IT artifacts to motivate voluntary contributions in online communities. We propose a dynamic approach, which allows the effect of motivating mechanisms to change across users over time. We characterize the dynamics of user contributions using a hidden Markov model (HMM) with latent motivation states under the public goods framework. We focus on three motivating mechanisms on transitioning users between the latent states: reciprocity, peer recognition, and self-image. Based on Bayesian estimation of the model with user-level panel data, we identify three motivation states (low, medium, and high), and show that the motivating mechanisms, implemented through various IT artifacts, could work differently across states. Specifically, reciprocity is only effective to transition users from low to medium motivation state, whereas peer recognition can boost all users to higher states. And self-image shows no effect when a user is already in high motivation state, although it helps users in low and medium states move to the high state. Design simulations on our structural model provide additional insights into the consequences of changing specific IT artifacts. These findings offer implications for platform designers on how to motivate user contributions and build sustainable online communities.

The sentiment implied in user generated content represents the authors' personality, attitude, education level and social status. In Crowdfunding, the sentimental factor of the text description may impact the backers' investment intention on the project. The authors study the textual description from the sentimental aspect on the pledge results by employing text mining. The study proves that positive sentiment in the blurb and detailed description promotes the successful campaigns while it should not contain any sentimental factor in title. The predictive analysis shows that the predictive accuracy can be improved 7% based on the baseline model after considering sentimental factors from 64.4% to 71.7%.

Parkinson's disease (PD) is recognized as the most common neurodegenerative movement disorder and results in debilitating motor deficits. The accumulation and spread of neurotoxic synuclein aggregates in the form of Lewy bodies is a key pathological feature of PD. Chronic activation of the NLRP3 inflammasome by protein aggregates is emerging as a major pathogenic mechanism in progressive neurodegenerative disorders and is considered an important therapeutic target. Recently the ketone body, β-hydroxy butyrate (BHB), was shown to efficiently inhibit the NLRP3 inflammasome in macrophages, and in vivo models of inflammatory disease. Furthermore, BHB can readily cross the blood brain barrier suggesting that it could have therapeutic benefits for the management of PD. In this study, we evaluated if BHB could inhibit chronic microglial inflammasome activation induced by pathological fibrillar synuclein aggregates. Interestingly, we found that BHB treatment almost completely blocked all aspects of inflammasome activation and pyroptosis induced by ATP and monosodium urate (MSU) crystals, consistent with previously published reports in macrophages. Surprisingly however, BHB did not inhibit inflammasome activation and release of IL-1β or caspase-1 induced by synuclein fibrils. Our results demonstrate that BHB does not block the upstream pathways regulating inflammasome activation by synuclein fibrils and suggest that synuclein mediated inflammasome activation proceeds via distinct mechanisms compared to traditional NLRP3 activators such as ATP and MSU.

We examine whether the Public Company Accounting Oversight Board (PCAOB) international inspection program improves audit quality for a sample of non-US-listed foreign public client companies from 55 countries audited by foreign (i.e., non-US) auditors. For a sample of non-US-listed clients of PCAOB-registered foreign auditors, we find that initial PCAOB inspections improve audit quality, over and above the threat of such inspections, for foreign auditors’ non-US-listed foreign clients. Our findings document the benefits of PCAOB international inspections for foreign investors in non-US-listed foreign companies which could increase the acceptability of the PCAOB international inspection program abroad.

The practice of providing quarterly earnings guidance has been criticized for encouraging investors to fixate on short-term earnings and encouraging managerial myopia. Using data from the post–Regulation Fair Disclosure period, we examine whether the cessation of quarterly earnings guidance reduces short-termism among investors. We show that, after guidance cessation, investors in firms that stop quarterly guidance are composed of a larger (smaller) proportion of long-term (short-term) institutions, put more (less) weight on long-term (short-term) earnings in firm valuation, become more (less) sensitive to analysts’ long-term (short-term) earning forecast revisions, and are less likely to dismiss chief executive officers for missing quarterly earnings targets by small amounts, relative to investors in firms that continue to issue quarterly earnings guidance. Our study provides new evidence of the benefit of stopping quarterly earnings guidance, that is, the reduction of short-termism among investors.

Human mitochondrial DNA (mtDNA) provides a promising target for microbial source tracking because it is unique to humans and universal across human individuals. We developed a droplet digital PCR (ddPCR) assay, hCYTB484, targeting the cytochrome b gene of the human mtDNA and compared the performance of the hCYTB484 assay with a widely used assay targeting human-associated Bacteroides, the HF183/BacR287 assay. We also defined and validated the analytical limit of detection and analytical lower limit of quantification; these analytical limits determine the concentration levels above which samples are declared to be positive and quantifiable for the target, respectively. We found both assays to be highly specific (95%) against cow and pig feces; however, the hCYTB484 was more sensitive when tested against individual human feces from US, Bangladesh, and Mozambique (100% versus a mean of 51% across the 3 countries). To further compare the performance of the two assays, we utilized a receiver operating characteristic curve, showing that the hCYTB484 marker was widely distributed across human feces from the 3 different geographical regions tested and in higher quantities than the HF183/BacR287 marker. The higher performance of the hCYTB484 marker in individual feces is a desirable characteristic in the detection of fecal pollution from sources to which fewer individuals contribute, such as non-sewered types of sanitation that serve most of Earth’s population and carry the highest risk of exposure to fecal-oral pathogens.ImportanceThe usefulness of an ideal human-specific, culture- and library-independent marker to the microbial source tracking field is reflected by the numerous efforts to develop such markers; however, thus far, microbial-based markers of this type have exhibited variable source-specificity across geographies and variable sensitivity across scales of fecal waste. Most of the world’s population is served by non-sewered forms of sanitation that also carry the highest risk of exposure to fecal-oral pathogens. This reality underscores the need for markers of human fecal contamination that have high sensitivity in fecal pollution sources to which fewer individuals contribute to, such as fecal sludges found in pit latrines. We show that human mtDNA-based methods can be highly source-specific and highly sensitive in smaller scales of fecal pollution, providing a useful addition to the microbial source tracking toolbox by complementing the variable performance of microbial-based markers.

Hybrid 2.5-D field solvers have been successfully applied to the analysis of high-speed printed circuit boards (PCB) and electronic packages. To enable electromagnetic interference and electromagnetic compatibility analysis, the solver needs to calculate the electromagnetic radiation in the near-field and far-field regions of the structure efficiently and accurately. We present two enhancements to the radiation calculations. The first is to use fast algorithms to accelerate the near-field and far-field calculations and the second is to correct the trace radiations by including the effect of the dielectric substrate. We demonstrate the accuracy and efficiency of these enhancements with three simulation examples.

Short-term load forecasting is an important issue in energy management system and a key measure to maintain the stable and effective operation of power systems, providing reasonable future load curve feeding to the unit commitment and economic load dispatch. Specifically, load forecasting at different time scales has various and corresponding roles in power systems. In recent years, plug-in electric vehicles have gradually become popular in major cities, and the number of electric vehicles is growing rapidly. However, the mass roll out of EVs may cause severe problems to the power system due to the huge charging power and stochastic charging behaviours of the EVs drivers. The accurate model of EVs charging load forecasting is therefore an emerging topic. In this paper, artificial neural networks and a long short term memory model based deep learning approaches are employed and compared in forecasting the EVs charging load from the charging station perspective. Numerical results show that the long short term memory model has demonstrated better performance and provided a model of higher accuracy in short-term EVs load forecasting comparing with the traditional artificial neural networks.

We examine the impact of social capital in local communities on corporate disclosure of proprietary information. Firms located in communities with higher social capital care more about the collective interests of the local communities. While the disclosure of proprietary information has the benefit of improving stock prices, the proprietary information revealed can be exploited by the firm’s product market rivals to its disadvantage and impose significant costs on both investors and the local community. Thus, when managers take the interests of local communities into consideration, they will view the disclosure of proprietary information to be a more costly action compared to those who only consider investors’ interests alone. Our empirical analysis confirms that firms located in communities with higher levels of social capital are associated with less disclosure of proprietary information. In addition, we find that the negative association between social capital and the disclosure of proprietary information is more pronounced for firms facing higher proprietary cost, with lower external financing dependence or with higher long-term institutional ownership.

2507 Background: C-CAR039 has been developed as a novel 2nd generation 4-1BB bi-specific CAR-T targeting both CD19 and CD20 antigens with an optimized bi-specific antigen binding domain. C-CAR039 can eradicate CD19/CD20 single or double positive tumor cells in vitro and in vivo. The tissue cross reactivity and whole genome membrane proteome array studies further confirmed the specificity of C-CAR039. Methods: GMP manufacturing of C-CAR039 was carried out in a serum free and fully closed semi-automatic system. Dose escalation and expansion studies were conducted to evaluate the safety and efficacy of C-CAR039 in r/r B-NHL patients. C-CAR039 was administered as a single intravenous dose after a 3-day cyclophosphamide plus fludarabine conditioning regimen. Results: As of 1/31/2021, 28 patients were infused and 25 (DLBCL, n = 22; PMBCL, n = 1; tFL, n = 1; FL, n = 1) were evaluable for safety and efficacy at dose ranges of 1.0 x 106 to 5.0x106 CAR-T cells/kg. The median age was 54 (range, 28-71) years, median number of prior lines of therapy was 3 (range, 1–5), 76% (19/25) of patients were in Ann Arbor Stage III/IV, and 80% (20/25) were refractory to their last treatment. 5 patients (20%) received bridging therapy. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to ASTCT 2019 criteria. Of the 25 patients, 24 (96%) experienced CRS, 23 (92%) were grade 1 or 2, 1 patient was grade 3. Median time to onset of CRS was 3 days (range, 0-10), with median duration of 4 days (range, 1-25). 2 patients had a grade 1 ICANS. Grade≥3 neutropenia, anemia, thrombocytopenia and infection were reported in 88%, 40%, 16% and 0% of patients, respectively. The best overall response rate was 92%, complete response (CR) rate was 84% and median time to response was 1.0 month (range, 0.9-1.2). With a median follow-up of 5.3 months, 76% remained in CR. Kaplan Meyer estimation of PFS at 6 months was 87.3% (95% CI, 71.2 to 100.0). Median duration of response has not been reached. Furthermore, C-CAR039 showed an encouraging cellular kinetic profile. In 25 evaluable patients, the median Tmax was 11 day, the median Cmax was 139,497 copies/mg gDNA, and the median AUC0̃28DAY of 1,673,844 day*copies/μg gDNA. Conclusions: C-CAR039 demonstrated a favorable safety profile and promising efficacy in this early clinical trial in patients with r/r B-NHL that might allow it to differentiate from existing therapies. The early clinical efficacy signal is encouraging and compares favorably to anti-CD19 CAR-T and peer therapies. These findings will be evaluated in more patients with longer follow-up to confirm safety, efficacy and duration of response. Clinical trial information: NCT04317885 , NCT04655677 , NCT04696432 , NCT04693676 .

Existing studies on task recommendation in crowdsourcing systems provide additional insights into the field from their perspectives, methodologies, frameworks, and disciplines, resulting in a highly productive but unorganized knowledge domain. This paper is motivated to exploit bibliometric techniques to derive insights that exceed the boundaries of individual systems and identify the potentially transformative changes from 268 published articles. The explicit features (i.e., affiliation, author, citation, and keywords) and implicit information (i.e., topic distribution, potential structure, hidden insights, and evolutionary trend) of domain literature are discovered by network analysis, cluster analysis, and timeline analysis. We summarize the generic framework based on knowledge domain structure and highlight the position of knowledge source, especially textual information, in task recommendation models. Drawing on the Shneider four-stage model, the temporal evolution trend is graphically illustrated to emphasize avenues for future research. Our study conveys accumulated and synthesized specialty knowledge to researchers or newcomers to help them design, initiate, implement, manage, and evaluate recommender systems in crowdsourcing.

The criteria for evaluating a crowdfunding project vary from person to person. Some investors are concerned with the entrepreneurs' profiles, while others are more interested in the creativity behind the project or the idea. Most investors evaluate a project by referring to founder-generated content. Entrepreneurs then face the choice of emphasizing their own profiles or the project creativity within the limited narrative. Our study is thus motivated to examine how the emphasis of the text narratives affect the fundraising outcomes. We propose an improved deep learning model for text content emphasis (TCE) detection from various textual sources, including titles, blurbs, and detailed descriptions, and then estimate the impact of TCE on the success of fundraising campaigns. With data collected from public sources of Kickstarter platform, our empirical analyses demonstrate that TCE matters differently for various textual sources. It is more effective for the title and blurb to emphasize the entrepreneur profile, while the detailed description should highlight the idea creativity. Furthermore, for the detailed description, the entrepreneur profile has a more positive effect when it is placed at the beginning of the narrative. And the effects of entrepreneur-oriented narratives are more pronounced in these projects with more social connections. This study contributes to the understanding of TCE, entrepreneur profile disclosure, and social connection in economic exchanges in online crowdfunding.

This study examines how PCAOB international inspections of non-U.S. auditors affect international Merger and Acquisition (M&A) outcomes. We find that clients of inspected auditors are more likely to become acquisition targets after the public disclosure of auditor's inspection report. We also find that deal completion is more likely and deal announcement returns are higher if deals involve targets with auditors for which inspection reports are available. Engagement deficiencies and unremediated quality control deficiencies identified in inspection reports weaken the positive effect of PCAOB oversight on M&A outcomes. Collectively, our results suggest that PCAOB oversight reduces information uncertainty in M&A deals.

In this cross-country study, we draw on the dividend liquidity hypothesis and the political economy literature to examine whether political institutions affect the relationship between stock market liquidity and a firm’s dividend policy. In countries with weak political institutions, we expect that investors are less able to demand higher dividends for stocks with low liquidity. Using a sample of 52 countries, we show that the negative association between stock market liquidity and dividends is more pronounced in countries with sound political institutions, consistent with the “outcome” model of dividends. These results are stronger in countries with better legal institutions and weaker for firms with financial constraints.

Background Men with prostate cancer are often castrated with long-acting injectable drugs termed androgen deprivation therapy (ADT). Although many benefit, ADT is also used in patients with little or nothing to gain. The best ways to stop this practice are unknown, and range from blunt pharmacy restrictions to informed decision-making. This study will refine and pilot two different de-implementation strategies for reducing ADT use among those unlikely to benefit in preparation for a comparative effectiveness trial. Methods/design This innovative mixed methods research program has three aims. Aim 1: To assess preferences and barriers for de-implementation of chemical castration in prostate cancer. Guided by the theoretical domains framework (TDF), urologists and patients from facilities with the highest and lowest castration rates across the VA will be interviewed to identify key preferences and de-implementation barriers for reducing castration as prostate cancer treatment. This qualitative work will inform Aim 2 while gathering rich information for two proposed pilot intervention strategies. Aim 2: To use a discrete choice experiment (DCE), a novel barrier prioritization approach, for de-implementation strategy tailoring. The investigators will conduct national surveys of urologists to prioritize key barriers identified in Aim 1 for stopping incident castration as localized prostate cancer treatment using a DCE experiment design. These quantitative results will identify the most important barriers to be addressed through tailoring of two pilot de-implementation strategies in preparation for Aim 3 piloting. Aim 3: To pilot two tailored de-implementation strategies to reduce castration as localized prostate cancer treatment. Building on findings from Aims 1 and 2, two de-implementation strategies will be piloted. One strategy will focus on formulary restriction at the organizational level and the other on physician/patient informed decision-making at different facilities. Outcomes will include acceptability, feasibility, and scalability in preparation for an effectiveness trial comparing these two widely varying de-implementation strategies. Discussion Our innovative approach to de-implementation strategy development is directly aligned with state-of-the-art complex implementation intervention development and implementation science. This work will broadly advance de-implementation science for low value cancer care, and foster participation in our de-implementation evaluation trial by addressing barriers, facilitators, and concerns through pilot tailoring. Trial registration ClinicalTrials.gov Identifier: NCT03579680, First Posted July 6, 2018.

The open-source software (OSS) production model has been gaining ground and even expanding to a broader class of products. A central virtue of OSS is co-creation through contributions and feedback from the user community, yet our knowledge of how to coordinate and maximize the benefit of such co-creation for market success is limited. In this paper, we propose that deliberate product release timing can be an important capability to orchestrate open source community contributions and maximize their benefit. We develop, formalize, and estimate a dynamic structural model to study the impact of product release management as a coordinating mechanism in peer production. We find that a deliberate and moderate release frequency, contingent on the installed base of the project, its quality enhancement, and the license type of the software, contributes to project success. Our results show that it would be optimal for early-stage projects to release more often. As the installed base increases, it is beneficial to release less often. We also find that there exists a curvilinear (inverse-U) relationship between the release frequency and the community contributions. Hence, excessive releasing may risk exhausting the community. Furthermore, even though the project may benefit from a new release, there also exists a release cost. The OSS team then has to balance between the two by carefully managing the release pace. We also find that projects with different license types may have different optimal release timing. These results may have important implications for managing technology-enabled, crowd-based collaboration in open innovation communities beyond open-source software development, launch, and adoption.

We examine whether monitors are likely to compromise their monitoring objectivity in the face of economically important clients in international business settings. In the context of external auditing and assurance services, we measure monitor objectivity by whether auditors are more (or less) likely to issue to their important clients modified audit opinions, that is, audit opinions provided to outside investors about the firm that demotes explicit areas of concern. Using a large cross-country sample, we document that auditors are more likely to issue modified opinions to their economically important clients relative to other clients. Furthermore, we find that this association is stronger (1) for Big N auditors, (2) for multinational audit clients, and (3) in countries with stronger legal regimes. These results suggest that monitors prioritize the protection of their reputation over lucrative economic relationships, and such information certification function is more pronounced for international auditors, multinational client firms, and in strong legal regimes.

Precursor field theory has been developed to describe the dynamics of electromagnetic field evolution in causally attenuative and dispersive media. In Debye dielectrics, the so-called Brillouin precursor exhibits an algebraic attenuation rate that makes it an ideal pulse waveform for communication, sensing, and imaging applications. Inspired by these studies in the electromagnetic domain, the present paper explores the propagation of acoustic precursors in dispersive media, with emphasis on biological media. To this end, a recently proposed causal dispersive model is employed, based on its interpretation as the acoustic counterpart of the Cole-Cole model for dielectrics. The model stems from the fractional stress-strain relation, which is consistent with the empirically known frequency power-law attenuation in viscoelastic media. It is shown that viscoelastic media described by this model, including human blood, support the formation and propagation of Brillouin precursors. The amplitude of these precursors exhibits a sub-exponential attenuation rate as a function of distance, actually being proportional to z-p, where z is the distance traveled within the medium and 0.5

This paper investigates the effect of the Asian financial crisis on the relationship between client economic importance and auditor independence. Using data from 1994 to 2001 in six Asian markets (Hong Kong, Indonesia, Malaysia, Singapore, Taiwan and Thailand), we find that auditors are less likely to compromise their independence for important clients after a crisis. The result is consistent with Coffee's (2001) crash-then-law hypothesis and supports the notion that financial crisis triggers public concern over auditors’ independence. Furthermore, we find the effect of financial crisis on auditor independence is more pronounced in weaker investor protection regimes.

Youyou Tu won the Nobel Prize, yet she failed to be nominated for China's own State Science and Technology (S&T) Awards. This has triggered a fierce debate on the S&T Award evaluation system in China. S&T awards are determined by bureaucrats and social circles (“guanxi”) ([ 1 ][1]). Because the system lacks transparency and allows no input from citizens or scientists, it is prone to opaque operations and influence by cronyism, favoritism, and bureaucracy. This has contaminated the science culture in China. Scientists feel obligated to develop “guanxi” networks instead of focusing on scientific discovery. A large portion of the country's science budget was estimated to have been wasted on networking dinners instead of invested in research labs ([ 1 ][1], [ 2 ][2]). Such priorities lead to scientific corruption and fraud ([ 3 ][3]). If nothing changes, talented scientists and scientific breakthroughs will continue to be suppressed. It is time for China to reform its S&T evaluation system. It should depend on merit, transparency, peer reviews, and objective measures. True participation by the science community should be institutionalized. The government should detach itself from the process. Decision-makers should consult with international academic circles and nongovernmental organizations. This new system is feasible with the availability of the Internet and social media. Making these changes will set an example for other countries that suffer from issues similar to China's. 1. [↵][4]1. Y. G. Shi, 2. Y. Rao , Science 329, 1128 (2010). [OpenUrl][5][Abstract/FREE Full Text][6] 2. [↵][7]1. Y. Xie, 2. C. Zhang, 3. Q. Lai , Proc. Natl. Acad. Sci. U.S.A. 111, 9437 (2014). [OpenUrl][8][Abstract/FREE Full Text][9] 3. [↵][10]1. C. Cao, 2. N. Li, 3. X. Li, 4. L. Liu , Science 341, 460 (2013). [OpenUrl][11][Abstract/FREE Full Text][12] [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #xref-ref-1-1 "View reference 1 in text" [5]: {openurl}?query=rft.jtitle%253DScience%26rft.stitle%253DScience%26rft.aulast%253DShi%26rft.auinit1%253DY.%26rft.volume%253D329%26rft.issue%253D5996%26rft.spage%253D1128%26rft.epage%253D1128%26rft.atitle%253DChina%2527s%2BResearch%2BCulture%26rft_id%253Dinfo%253Adoi%252F10.1126%252Fscience.1196916%26rft_id%253Dinfo%253Apmid%252F20813923%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [6]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEzOiIzMjkvNTk5Ni8xMTI4IjtzOjQ6ImF0b20iO3M6MjU6Ii9zY2kvMzUxLzYyNzgvMTE2MS4xLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ== [7]: #xref-ref-2-1 "View reference 2 in text" [8]: {openurl}?query=rft.jtitle%253DProc.%2BNatl.%2BAcad.%2BSci.%2BU.S.A.%26rft_id%253Dinfo%253Adoi%252F10.1073%252Fpnas.1407709111%26rft_id%253Dinfo%253Apmid%252F24979796%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [9]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czoxMToiMTExLzI2Lzk0MzciO3M6NDoiYXRvbSI7czoyNToiL3NjaS8zNTEvNjI3OC8xMTYxLjEuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9 [10]: #xref-ref-3-1 "View reference 3 in text" [11]: {openurl}?query=rft.jtitle%253DScience%26rft.stitle%253DScience%26rft.aulast%253DCao%26rft.auinit1%253DC.%26rft.volume%253D341%26rft.issue%253D6145%26rft.spage%253D460%26rft.epage%253D462%26rft.atitle%253DReforming%2BChina%2527s%2BS%2526T%2BSystem%26rft_id%253Dinfo%253Adoi%252F10.1126%252Fscience.1234206%26rft_id%253Dinfo%253Apmid%252F23908209%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [12]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEyOiIzNDEvNjE0NS80NjAiO3M6NDoiYXRvbSI7czoyNToiL3NjaS8zNTEvNjI3OC8xMTYxLjEuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9

The bullwhip effect is a major source of supply chain inefficiency. Whereas prior literature has identified a number of potential contributing factors and recommended such remedies as information sharing enabled by information technology (IT) or electronic linkage (EL), few studies have provided empirical support. We use industry-level data to examine whether EL use with buyer and supplier industries helps reduce the bullwhip effect as measured by inventory–demand variance ratio. Our major findings are that (1) EL use with supplier industries reduces the bullwhip effect, whereas (2), surprisingly, EL use with buyer industries increases it, but (3) this adverse effect tends to be mitigated by IT use. These findings point to the possible asymmetric effects of EL use in supply chains and provide a different perspective to the existing conclusions in the literature that EL use improves performance. Combining the above results, we have learned that the use of EL tends to behave differently depending on whether it is used upstream or downstream in the supply chain. This also sheds light on the conditions under which such investment may be more (or less) beneficial.