WoZ Pilot Experiment for Empathic Robotic Tutors: Opportunities and Challenges

We discuss the challenges and opportunities in building empathic robotic tutors based on a preliminary Wizard-of-Oz (WoZ) pilot study. From the data collected in this study, we identify situations where empathy in a robotic tutor could have helped the conversation between the learner and the tutor. The video presented with this paper captures these situations where two children participants are interacting with a map application and a robot tutor operated by a wizard

Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling

Chronic activation of stress hormones such as glucocorticoids leads to skeletal muscle wasting in mammals. However, the molecular events that mediate glucocorticoid-induced muscle wasting are not well understood. Here, we show that SIRT6, a chromatin-associated deacetylase indirectly regulates glucocorticoid-induced muscle wasting by modulating IGF/PI3K/AKT signaling. Our results show that SIRT6 levels are increased during glucocorticoid-induced reduction of myotube size and during skeletal muscle atrophy in mice. Notably, overexpression of SIRT6 spontaneously decreases the size of primary myotubes in a cell-autonomous manner. On the other hand, SIRT6 depletion increases the diameter of myotubes and protects them against glucocorticoid-induced reduction in myotube size, which is associated with enhanced protein synthesis and repression of atrogenes. In line with this, we find that muscle-specific SIRT6 deficient mice are resistant to glucocorticoid-induced muscle wasting. Mechanistically, we find that SIRT6 deficiency hyperactivates IGF/PI3K/AKT signaling through c-Jun transcription factor-mediated increase in IGF2 expression. The increased activation, in turn, leads to nuclear exclusion and transcriptional repression of the FoxO transcription factor, a key activator of muscle atrophy. Further, we find that pharmacological inhibition of SIRT6 protects against glucocorticoid-induced muscle wasting in mice by regulating IGF/PI3K/AKT signaling implicating the role of SIRT6 in glucocorticoid-induced muscle atrophy.Fil: Mishra, Sneha. No especifíca;Fil: Cosentino, Claudia. Harvard Medical School; Estados UnidosFil: Tamta, Ankit Kumar. No especifíca;Fil: Khan, Danish. No especifíca;Fil: Srinivasan, Shalini. No especifíca;Fil: Ravi, Venkatraman. No especifíca;Fil: Abbotto, Elena. Università degli Studi di Genova; ItaliaFil: Arathi, Bangalore Prabhashankar. No especifíca;Fil: Kumar, Shweta. No especifíca;Fil: Jain, Aditi. No especifíca;Fil: Ramaian, Anand S.. No especifíca;Fil: Kizkekra, Shruti M.. No especifíca;Fil: Rajagopal, Raksha. No especifíca;Fil: Rao, Swathi. No especifíca;Fil: Krishna, Swati. No especifíca;Fil: Asirvatham Jeyaraj, Ninitha. Indian Institute of Technology; IndiaFil: Haggerty, Elizabeth R.. Harvard Medical School; Estados UnidosFil: Silberman, Dafne Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Kurland, Irwin J.. No especifíca;Fil: Veeranna, Ravindra P.. No especifíca;Fil: Jayavelu, Tamilselvan. No especifíca;Fil: Bruzzone, Santina. Università degli Studi di Genova; ItaliaFil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosFil: Sundaresan, Nagalingam R.. No especifíca

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Acquisitions and Foreign Competition

I provide evidence on the impact of foreign competition on firms' propensities to engage in mergers and acquisitions. Using import tariff reductions as an exogenous shock that increases foreign industry competition, I find that affected firms are more likely to make acquisitions following a tariff reduction. Cross-sectional tests show that this association is more pronounced for single segment firms, firms that innovate less, or that are more capital intensive, which suggests this association is stronger for firms which stand to gain more from an acquisition. Moreover, the positive relationship between acquisition likelihood and tariff cuts is less pronounced for financially constrained firms and during times of low capital liquidity, which implies that it is easier for firms with greater access to external capital to respond to increases in foreign competition by making acquisitions. Finally, I find that acquisitions made subsequent to tariff decreases are associated with positive wealth gains for bidder shareholders, indicating that these acquisitions are viewed favorably by market participants

The Impact of Smoking Cigarettes or E-Cigarettes on Sleep Quality: A Literature Review

Smoking is common among adults of all ages. Decades of research have shown that smoking is linked to side effects such as lung cancer. This study aims to systematically review how smoking is linked to sleep. Database searches were done through Web of Science and Google Scholar. A total of 19 peer-reviewed journals were referenced to conduct this literature review. 15 peer-reviewed journals were used for the results. Results demonstrated that smoking was found to be correlated with sleep deprivation in both males and females of all ages. Environmental Tobacco Smoke (ETS) was a source of non-smokers' sleep complaints. Although there are multiple kinds of cigarettes, sleep quality has been shown to be poor regardless of the smoking medium. Ceasing smoking may lead to sleep benefits. Additional research will need to be conducted to further corroborate this statement

Private and Robust Aggregate Statistics Collection with Shamir-Secret Sharing

Today's world is filled with smartwatches and smartphones which collect data every second of every day. The data collected from the user of such devices, the client, and is being accessed by the creator of the applications on the devices at the servers. The client's data is sensitive and private (e.g., its current location), and the servers need only the statistical functions over the values of all clients (e.g., the most popular location). The existing work Prio [\cite{DBLP:journals/corr/Corrigan-GibbsB17}] presents a privacy-preserving protocol for the collection of aggregate statistics. Their protocol ensures that the client's private data is protected as long as at least one server is honest. However, it is only robust against malicious clients and not against malicious servers. In particular, even a single malicious server can arbitrarily change the aggregate output. In this work, we present a new protocol that guarantees data privacy as well as system robustness in the presence of both malicious clients and malicious servers as long as a majority of the servers are honest. Our new protocol extends the Prio protocol by introducing Shamir secret sharing in place of additive secret sharing