Deception and false belief in paranoia: Modelling Theory of Mind stories

Background. This study used Item Response Theory (IRT) to model the psychometric properties of a Theory of Mind (ToM) stories task. The study also aimed to determine whether the ability to understand states of false belief in others and the ability to understand another's intention to deceive are separable skills, and to establish which is more sensitive to the presence of paranoia.

Method. A large and diverse clinical and nonclinical sample differing in levels of depression and paranoid ideation performed a ToM stories task measuring false belief and deception at first and second order.

Results. A three-factor IRT model was found to best fit the data, consisting of first- and second-order deception factors and a single false-belief factor. The first-order deception and false-belief factors had good measurement properties at low trait levels, appropriate for samples with reduced ToM ability. First-order deception and false beliefs were both sensitive to paranoid ideation with IQ predicting performance on false belief items.

Conclusions. Separable abilities were found to underlie performance on verbal ToM tasks. However, paranoia was associated with impaired performance on both false belief and deception understanding with clear impairment at the simplest level of mental state attribution.     

The Portal of Geriatrics Online Education: A 21st‐Century Resource for Teaching Geriatrics

The way students are taught and evaluated is changing, with greater emphasis on flexible, individualized, learner‐centered education, including the use of technology. The goal of assessment is also shifting from what students know to how they perform in practice settings. Developing educational materials for teaching in these ways is time‐consuming and can be expensive. The Portal of Geriatrics Online Education (POGOe) was developed to aid educators in meeting these needs and become quicker, better‐prepared teachers of geriatrics. POGOe contains more than 950 geriatrics educational materials that faculty at 45% of allopathic and 7% of osteopathic U.S. medical schools and the Centers for Geriatric Nursing Excellence have created. These materials include various instructional and assessment methodologies, including virtual and standardized patients, games, tutorials, case‐based teaching, self‐directed learning, and traditional lectures. Materials with common goals and resource types are available as selected educational series. Learner assessments comprise approximately 10% of the educational materials. POGOe also includes libraries of videos, images, and questions extracted from its educational materials to encourage educators to repurpose content components to create new resources and to align their teaching better with their learners' needs. Web‐Geriatric Education Modules, a peer‐reviewed online modular curriculum for medical students, is a prime example of this repurposing. The existence of a robust compendium of instructional and assessment materials allows educators to concentrate more on improving learner performance in practice and not simply on knowledge acquisition. It also makes it easier for nongeriatricians to teach the care of older adults in their respective disciplines.     

MDX‐1097 induces antibody‐dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide

MDX‐1097 is an antibody specific for a unique B cell antigen called kappa myeloma antigen (KMA) that consists of cell membrane‐associated free kappa light chain (κFLC). KMA was detected on kappa human multiple myeloma cell lines (κHMCLs), on plasma cells (PCs) from kappa multiple myeloma (κMM) patients and on κPC dyscrasia tissue cryosections. In primary κMM samples, KMA was present on CD38+ cells that were CD138 and CD45 positive and/or negative. MDX‐1097 exhibited a higher affinity for KMA compared to κFLC and the latter did not abrogate binding to KMA. MDX‐1097‐mediated antibody‐dependent cellular cytotoxicity (ADCC) and in vitro exposure of target cells to the immunomodulatory drug lenalidomide resulted in increased KMA expression and ADCC. Also, in vitro exposure of peripheral blood mononuclear cells (PBMCs) to lenalidomide enhanced MDX‐1097‐mediated ADCC. PBMCs obtained from myeloma patients after lenalidomide therapy elicited significantly higher levels of MDX‐1097‐mediated ADCC than cells obtained prior to lenalidomide treatment. These data establish KMA as a relevant cell surface antigen on MM cells that can be targeted by MDX‐1097. The ADCC‐inducing capacity of MDX‐1097 and its potentiation by lenalidomide provide a powerful rationale for clinical evaluation of MDX‐1097 alone and in combination with lenalidomide.     

Antisense reduction of 11β-hydroxysteroid dehydrogenase type 1 enhances energy expenditure and insulin sensitivity independent of food intake in C57BL/6J mice on a Western-type diet

We recently reported that inhibition of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) by antisense oligonucleotide (ASO) improved hepatic lipid metabolism independent of food intake. In that study, 11β-HSD1 ASO-treated mice lost weight compared with food-matched control ASO-treated mice, suggesting treatment-mediated increased energy expenditure. We have now examined the effects of 11β-HSD1 ASO treatment on adipose tissue metabolism, insulin sensitivity, and whole-body energy expenditure. We used an ASO to knock down 11β-HSD1 in C57BL/6J mice consuming a Western-type diet (WTD). The 11β-HSD1 ASO-treated mice consumed less food, so food-matched control ASO-treated mice were also evaluated. We characterized body composition, gene expression of individual adipose depots, and measures of energy metabolism. We also investigated glucose/insulin tolerance as well as acute insulin signaling in several tissues. Knockdown of 11β-HSD1 protected against WTD-induced obesity by reducing epididymal, mesenteric, and subcutaneous white adipose tissue while activating thermogenesis in brown adipose tissue. The latter was confirmed by demonstrating increased energy expenditure in 11β-HSD1 ASO-treated mice. The 11β-HSD1 ASO treatment also protected against WTD-induced glucose intolerance and insulin resistance; this protection was associated with smaller cells and fewer macrophages in epididymal white adipose tissue as well as enhanced in vivo insulin signaling. Our results indicate that ASO-mediated inhibition of 11β-HSD1 can protect against several WTD-induced metabolic abnormalities. These effects are, at least in part, mediated by increases in the oxidative capacity of brown adipose tissue.     

Beat-to-beat variability of repolarization as a new biomarker for proarrhythmia in vivo

Pharmacological safety evaluation of (pro) drugs includes cardiac safety assessment of proarrhythmic liability in healthy tissue with emphasis on the rapid component of the delayed rectifier (I(Kr)). The lack of (1) an arrhythmic end point, (2) tests in remodeled, predisposed tissue, and (3) testing chronic drug influence on channel trafficking impairs on the drawn conclusions of these assays regarding drug safety. Moreover, the currently used human ether-à-go-go-related gene assays, action potential duration, prolongation in multicellular preparations, or the QT interval have significant shortcomings in their prediction of an increased risk for drug-induced torsades de pointes arrhythmia. In this review, it will be proposed that beat-to-beat variability of repolarization quantified as short-term variability can (1) discriminate between safe and unsafe drugs even under predisposed and highly arrhythmogenic conditions despite accompanying QT prolongation and (2) identify the individual at risk for subsequent arrhythmic events.     

Patient-initiated device removal in intensive care units: a national prevalence study

OBJECTIVE: Information is needed about patient-initiated device removal to guide quality initiatives addressing regulations aimed at minimizing physical restraint use. Research objectives were to determine the prevalence of device removal, describe patient contexts, examine unit-level adjusted risk factors, and describe consequences. DESIGN: Prospective prevalence. SETTING: Total of 49 adult intensive care units (ICUs) from a random sample of 39 hospitals in five states. METHODS: Data were collected daily for 49,482 patient-days by trained nurses and included unit census, ventilator days, restraint days, and days accounted for by men and by elderly. For each device removal episode, data were collected on demographic and clinical variables. RESULTS: Patients removed 1,623 devices on 1,097 occasions: overall rate, 22.1 episodes/1000 patient-days; range, 0-102.4. Surgical ICUs had lower rates (16.1 episodes) than general (23.6 episodes) and medical (23.4 episodes) ICUs. ICUs with fewer resources had fewer all-type device removal relative to ICUs with greater resources (relative risk, 0.76; 95% confidence interval, 0.66-0.87) but higher self-extubation rates (relative risk, 1.27; 95% confidence interval, 1.07-1.52). Men accounted for 57% of the episodes, 44% were restrained at the time, and 30% had not received any sedation, narcotic, or psychotropic drug in the previous 24 hrs. There was no association between rates of device removal with restraint rates, proportion of men, or elderly. Self-extubation rates were inversely associated with ventilator days (rs = -0.31, p = .03). Patient harm occurred in 250 (23%) episodes; ten incurred major harm. No deaths occurred. Reinsertion rates varied by device: 23.5% of surgical drains to 88.9% of monitor leads. Additional resources (e.g., radiography) were used in 58% of the episodes. CONCLUSION: Device removal by ICU patients is common, resulting in harm in one fourth of patients and significant resource expenditure. Further examination of patient-, unit-, and practitioner-level variables may help explain variation in rates and provide direction for further targeted interventions.