Changing minds: Children's inferences about third party belief revision

By the age of 5, children explicitly represent that agents can have both true and false beliefs based on epistemic access to information (e.g., Wellman, Cross, & Watson, 2001). Children also begin to understand that agents can view identical evidence and draw different inferences from it (e.g., Carpendale & Chandler, 1996). However, much less is known about when, and under what conditions, children expect other agents to change their minds. Here, inspired by formal ideal observer models of learning, we investigate children's expectations of the dynamics that underlie third parties' belief revision. We introduce an agent who has prior beliefs about the location of a population of toys and then observes evidence that, from an ideal observer perspective, either does, or does not justify revising those beliefs. We show that children's inferences on behalf of third parties are consistent with the ideal observer perspective, but not with a number of alternative possibilities, including that children expect other agents to be influenced only by their prior beliefs, only by the sampling process, or only by the observed data. Rather, children integrate all three factors in determining how and when agents will update their beliefs from evidence.National Science Foundation (U.S.). Division of Computing and Communication Foundations (1231216)National Science Foundation (U.S.). Division of Research on Learning in Formal and Informal Settings (0744213)National Science Foundation (U.S.) (STC Center for Brains, Minds and Machines Award CCF-1231216)National Science Foundation (U.S.) (0744213

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Out-Of-Network Primary Care Is Associated With Higher Per Beneficiary Spending In Medicare ACOs

Despite expectations that Medicare accountable care organizations (ACOs) would curb health care spending, their effect has been modest. One possible explanation is that ACOs’ inability to prohibit out-of-network care limits their control over spending. To examine this possibility, we examined the association between out-of-network care and per beneficiary spending using national Medicare data for 2012–15. While there was no association between out-of-network specialty care and ACO spending, each percentage-point increase in receipt of out-of-network primary care was associated with an increase of $10.79 in quarterly total ACO spending per beneficiary. When we broke down total spending by place of service, we found that out-of-network primary care was associated with higher spending in outpatient, skilled nursing facility, and emergency department settings, but not inpatient settings. Our findings suggest an opportunity for the Medicare program to realize substantial savings, if policy makers developed explicit incentives for beneficiaries to seek more of their primary care within network

New Persistent Opioid Use after Outpatient Ureteroscopy for Upper Tract Stone Treatment.

OBJECTIVE: To measure the incidence of persistent opioid use following ureteroscopy (URS). Over 100 Americans die every day from opioid overdose. Recent studies suggest that many opioid addictions surface after surgery. METHODS: Using claims data, we identified adults who underwent outpatient URS for treatment of upper tract stones between January 2008 and December 2016 and filled an opioid prescription attributable to URS. We then measured the rate of new persistent opioid use-defined as continued use of opioids 91 to 180 days after URS among those who were previously opioid-naive. Finally, we fit multivariable models to assess whether new persistent opioid use was associated with the amount of opioid prescribed at the time of URS. RESULTS: In total, 27,740 patients underwent outpatient URS, 51.2% of whom were opioid-naïve. Nearly one in 16 (6.2%) opioid-naïve patients developed new persistent opioid use after URS. Six months following surgery, beneficiaries with new persistent opioid use continued to fill prescriptions with daily doses of 4.2 oral morphine equivalents. Adjusting for measured sociodemographic and clinical differences, patients in the highest tercile of opioids prescribed at the time of URS had 69% higher odds of new persistent opioid use compared to those in the lowest tercile (odds ratio, 1.69; 95% CI, 1.41 to 2.03). CONCLUSIONS: Nearly one in 16 opioid-naive patients develop new persistent opioid use after URS. New persistent opioid use is associated with the amount of opioid prescribed at the time of URS. Given these findings, urologists should re-evaluate their post-URS opioid prescribing patterns

Identification and characterization of tropomyosin 3 associated with granulin-epithelin precursor in human hepatocellular carcinoma.

BACKGROUND AND AIM: Granulin-epithelin precursor (GEP) has previously been reported to control cancer growth, invasion, chemo-resistance, and served as novel therapeutic target for cancer treatment. However, the nature and characteristics of GEP interacting partner remain unclear. The present study aims to identify and characterize the novel predominant interacting partner of GEP using co-immunoprecipitation and mass spectrometry. METHODS AND RESULTS: Specific anti-GEP monoclonal antibody was used to capture GEP and its interacting partner from the protein extract of the liver cancer cells Hep3B. The precipitated proteins were analyzed by SDS-PAGE, followed by mass spectrometry and the protein identity was demonstrated to be tropomyosin 3 (TPM3). The interaction has been validated in additional cell models using anti-TPM3 antibody and immunoblot to confirm GEP as the interacting partner. GEP and TPM3 expressions were then examined by real-time quantitative RT-PCR in clinical samples, and their transcript levels were significantly correlated. Elevated TPM3 levels were observed in liver cancer compared with the adjacent non-tumorous liver, and patients with elevated TPM3 levels were shown to have poor recurrence-free survival. Protein expression of GEP and TPM3 was observed only in the cytoplasm of liver cancer cells by immunohistochemical staining. CONCLUSIONS: TPM3 is an interacting partner of GEP and may play an important role in hepatocarcinogenesis

Detection of anti-premembrane antibody as a specific marker of four flavivirus serocomplexes and its application to serosurveillance in endemic regions

ABSTRACTIn the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT–PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate

Association of TPM3 and GEP.

<p>(A–B) Protein-protein interaction of TPM3 and GEP was validated by immunoprecipitation using anti-TPM3 antibody, followed with immunoblot detection using anti-GEP antibody in different cell lines (A) Hep3B and (B) HepG2 cells. (C) Positive correlation of GEP and TPM3 on protein level. AS: Cells suppressed for GEP by transfection with anti-sense GEP fragment; FL: Cells overexpressed for GEP by transfection with full-length (FL) GEP cDNA construct. Cells with overexpression of GEP showed elevated TPM3 levels, while suppression of GEP showed decreased TPM3.</p