In vivo effect of FK506 on human pancreatic islets

The purpose of this study was to evaluate the in vivo effect of FK506 on human pancreatic islets. Twenty-five nude mice were made diabetic by one intravenous injection of streptozotocin. Approximately 600 islets were administered in the renal subcapsular space 3-5 days following streptozotocin administration. One week after transplantation, the mice were divided in four groups. In group 1, the animals received 1 injection of 0.5 ml of diluent i.p. daily for one week. In groups 2, 3, and 4 the treatments were daily i.p. injection of 0.3, 1, and 3 mg/kg FK506, respectively. After treatment, the functional integrity of the transplanted human islets was tested by measuring the plasma glucose and human C-peptide response to intraperitoneal glucose injection in groups 1 and 4. IPGTT alone was assessed in groups 2 and 3. The results indicate that i.p. administration of FK506 for one week at a dose 0.3 mg/kg/day did not result in any significant alteration of glucose disappearance and C-peptide response to IPGTT. Higher doses of FK506 produced a significant delay in glucose disappearance in groups 3 and 4, and a significant inhibition of glucose-mediated C-peptide response in group 4. © 1991 by Williams and Wilkins

A Virtual Conversational Agent for Teens with Autism: Experimental Results and Design Lessons

We present the design of an online social skills development interface for teenagers with autism spectrum disorder (ASD). The interface is intended to enable private conversation practice anywhere, anytime using a web-browser. Users converse informally with a virtual agent, receiving feedback on nonverbal cues in real-time, and summary feedback. The prototype was developed in consultation with an expert UX designer, two psychologists, and a pediatrician. Using the data from 47 individuals, feedback and dialogue generation were automated using a hidden Markov model and a schema-driven dialogue manager capable of handling multi-topic conversations. We conducted a study with nine high-functioning ASD teenagers. Through a thematic analysis of post-experiment interviews, identified several key design considerations, notably: 1) Users should be fully briefed at the outset about the purpose and limitations of the system, to avoid unrealistic expectations. 2) An interface should incorporate positive acknowledgment of behavior change. 3) Realistic appearance of a virtual agent and responsiveness are important in engaging users. 4) Conversation personalization, for instance in prompting laconic users for more input and reciprocal questions, would help the teenagers engage for longer terms and increase the system's utility

Strangeness in Astrophysics and Cosmology

Some recent developments concerning the role of strange quark matter for astrophysical systems and the QCD phase transition in the early universe are addressed. Causality constraints of the soft nuclear equation of state as extracted from subthreshold kaon production in heavy-ion collisions are used to derive an upper mass limit for compact stars. The interplay between the viscosity of strange quark matter and the gravitational wave emission from rotation-powered pulsars are outlined. The flux of strange quark matter nuggets in cosmic rays is put in perspective with a detailed numerical investigation of the merger of two strange stars. Finally, we discuss a novel scenario for the QCD phase transition in the early universe, which allows for a small inflationary period due to a pronounced first order phase transition at large baryochemical potential.Comment: 8 pages, invited talk given at the International Conference on Strangeness in Quark Matter (SQM2009), Buzios, Brasil, September 28 - October 2, 200

Stoics against stoics in Cudworth's "A Treatise of Freewill"

In his 'A Treatise of Freewill', Ralph Cudworth argues against Stoic determinism by drawing on what he takes to be other concepts found in Stoicism, notably the claim that some things are ‘up to us’ and that these things are the product of our choice. These concepts are central to the late Stoic Epictetus and it appears at first glance as if Cudworth is opposing late Stoic voluntarism against early Stoic determinism. This paper argues that in fact, despite his claim to be drawing on Stoic doctrine, Cudworth uses these terms with a meaning first articulated only later, by the Peripatetic commentator Alexander of Aphrodisias

Comparison of SGA Oral Medications and a Long-Acting Injectable SGA: The PROACTIVE Study

Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician\u27s choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials

Random graphs with arbitrary degree distributions and their applications

Recent work on the structure of social networks and the internet has focussed attention on graphs with distributions of vertex degree that are significantly different from the Poisson degree distributions that have been widely studied in the past. In this paper we develop in detail the theory of random graphs with arbitrary degree distributions. In addition to simple undirected, unipartite graphs, we examine the properties of directed and bipartite graphs. Among other results, we derive exact expressions for the position of the phase transition at which a giant component first forms, the mean component size, the size of the giant component if there is one, the mean number of vertices a certain distance away from a randomly chosen vertex, and the average vertex-vertex distance within a graph. We apply our theory to some real-world graphs, including the world-wide web and collaboration graphs of scientists and Fortune 1000 company directors. We demonstrate that in some cases random graphs with appropriate distributions of vertex degree predict with surprising accuracy the behavior of the real world, while in others there is a measurable discrepancy between theory and reality, perhaps indicating the presence of additional social structure in the network that is not captured by the random graph.Comment: 19 pages, 11 figures, some new material added in this version along with minor updates and correction

Analysis of stimulant prescriptions and drug-related poisoning risk among persons receiving buprenorphine treatment for opioid use disorder

Importance: Stimulant medication use is common among individuals receiving buprenorphine for opioid use disorder (OUD). Associations between prescription stimulant use and treatment outcomes in this population have been understudied. Objectives: To investigate whether use of prescription stimulants was associated with (1) drug-related poisoning and (2) buprenorphine treatment retention. Design, Setting, and Participants: This retrospective, recurrent-event cohort study with a case-crossover design used a secondary analysis of administrative claims data from IBM MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Primary analyses were conducted from March 1 through August 31, 2021. Individuals aged 12 to 64 years with an OUD diagnosis and prescribed buprenorphine who experienced at least 1 drug-related poisoning were included in the analysis. Unit of observation was the person-day. Exposures: Days of active stimulant prescriptions. Main Outcomes and Measures: Primary outcomes were drug-related poisoning and buprenorphine treatment retention. Drug-related poisonings were defined using International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes; treatment retention was defined by continuous treatment claims until a 45-day gap was observed. Results: There were 13 778 567 person-days of observation time among 22 946 individuals (mean [SD] age, 32.8 [11.8] years; 50.3% men) who experienced a drug-related poisoning. Stimulant treatment days were associated with 19% increased odds of drug-related poisoning (odds ratio [OR], 1.19 [95% CI, 1.06-1.34]) compared with nontreatment days; buprenorphine treatment days were associated with 38% decreased odds of poisoning (OR, 0.62 [95% CI, 0.59-0.65]). There were no significant interaction effects between use of stimulants and buprenorphine. Stimulant treatment days were associated with decreased odds of attrition from buprenorphine treatment (OR, 0.64 [95% CI, 0.59-0.70]), indicating that stimulants were associated with 36% longer mean exposure to buprenorphine and its concomitant protection. Conclusions and Relevance: Among persons with OUD, use of prescription stimulants was associated with a modest increase in per-day risk of drug-related poisoning, but this risk was offset by the association between stimulant use and improved retention to buprenorphine treatment, which is associated with protection against overdose