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This narrative review explores current literature base detailing the effectiveness of alternative CPR instruction as compared to traditional CPR courses in the lay population. Assessment of alternative instructional methods found that video self-instruction and simplified CPR formats resulted in equivalent performance of CPR metrics and practical scenario assessment performance, as compared to traditional CPR instruction courses. While additional research is needed to further substantiate the value of self-directed learning, interactive digital, and abbreviated formats, these studies also suggested equivalence in CPR performance compared to traditional courses. In view of the importance of bystander CPR in OHCA outcomes, and the barriers presented by traditional CPR education courses, we recommend that public safety leaders and CPR educators strongly consider the introduction of these programs within their communities and classrooms.

Delay discounting refers to the decline in the present value of an outcome as a function of the delay to its receipt. Research on delay discounting initially focused on substance abuse, generally finding that greater delay discounting is associated with increased risk for and severity of substance abuse. More recently, delay discounting has been linked theoretically and empirically to affective psychopathology, potentially suggesting novel intervention targets for mental health problems such as depression and anxiety. Longitudinal research consequently is critical to determine direction of causality and rule out possible third variable explanations. Only a small number of longitudinal studies have been conducted in this area, however. Furthermore, socio-economic and socio-cultural factors may influence delay discounting and its effects, but thus far the literature is relatively limited in this regard. The present study focused on adolescence, a key time-period for development of delay discounting and emotional problems. Longitudinal relations between delay discounting, and depression and anxiety symptoms were assessed among 414 adolescents in Vietnam, a lower-middle-income Southeast Asian nation with significant cultural divergence from Western countries. In contrast to most cross-sectional studies that have found positive or non-significant correlations, in the present study delay discounting at Time 1 had a negative beta with anxiety and depression symptoms at Time 1, with preference for immediate but smaller rewards (higher discounting) at Time 1 associated with lower anxiety and depression symptoms at Time 2. These results suggest that under certain circumstances, steeper delay discounting may be adaptive and supportive of emotional mental health.

Online misinformation poses a significant threat to global challenges, such as the COVID-19 pandemic and climate change. Misinformation is disproportionality shared by people with extreme political attitudes, especially among the far right. To understand the psychological and neurocognitive processes that underlie misinformation sharing among extremists, we conducted a pre-registered, cross-cultural experiment with conservatives and far-right supporters in the US and Spain (N = 1,609) and a neuroimaging study with far-right supporters in Spain (N = 36). Individuals who felt their personal identity was fused with their political group were more likely to share misinformation, especially when the misinformation was related to issues that involve sacred moral values (e.g., immigration and nationalism). Analytical thinking was unrelated to misinformation sharing when the misinformation involved sacred values (vs. non-sacred values) and fact-checks had little or no effect in this sample, especially among hyper-partisans. Far-right supporters also showed increased activity in brain regions associated with theory of mind in response to posts with sacred values, highlighting the social dimension of misinformation sharing. These results suggest that political devotion plays a key role in misinformation sharing and that identity-based interventions may help curb misinformation for specific groups.

Failure to rescue (FTR) is an emerging measure in cardiac surgery, defined as mortality after a postoperative complication. We hypothesized that establishing a medical emergency team (MET) reduced rates of FTR in adults undergoing cardiac surgery.All patients (N = 11,218) undergoing a The Society of Thoracic Surgeons index operation at our center (1994-2018) were stratified by pre-MET or MET era based on the 2009 institutional implementation of a MET to respond to clinical decompensation in non-intensive-care patients. Patients missing The Society of Thoracic Surgeons predicted risk of mortality were excluded from all cohorts. Risk adjusted multivariable regression analyzed the association of postoperative complications, operative mortality, and FTR by era. Nearest neighbor propensity score matching utilizing patients' The Society of Thoracic Surgeons predicted risk of mortality was performed to create balanced control and exposure groups for secondary subgroup analysis.In the risk-adjusted multivariable analysis, surgery during the MET era was associated with decreased mortality (odds ratio [OR], 0.51; 95% CI, 0.45-0.77; P .001), postoperative renal failure (OR, 0.57; 95% CI, 0.46-0.70; P .001), reoperation (OR, 0.75; 95% CI, 0.59-0.95; P = .017), and deep sternal wound infection (OR, 0.16; 95% CI, 0.04-0.45; P = .002). Surgery performed during the MET era was associated with a decreased rate of FTR in the risk-adjusted analysis (OR, 0.46; 95% CI, 0.34-0.70; P .001).The development of an institutional MET program was associated with a decrease in major complications and FTR. These findings support the development of MET programs to improve FTR after cardiac surgery.

As educational technology advances, it is imperative that universities responsibly and appropriately adapt new approaches to enhance teaching and learning. Over a 6-month period, veterinary students at Ross University School of Veterinary Medicine (RUSVM) spearheaded the improvement of a proprietary prototype virtual interactive three-dimensional (3D), touch screen, canine anatomy table (APEX). Eight veterinary students with a grade of 80% or higher in their anatomy courses were hired as research assistants to identify and characterize 306 virtual anatomical structures. Descriptive statistics were used to assess students’ (1) accuracy in reviewing assigned anatomical structures, and (2) perceptions surrounding the use of APEX as an educational anatomical tool. The overall accuracy rating was 3.73 on a 4-point scale, and students reported their experience as enjoyable (median 4 on a 5-point Likert scale) and beneficial to their knowledge of veterinary anatomy (median 4). In addition, 29 RUSVM faculty were surveyed on both the prototype APEX table as well as the student-improved version. Faculty agreement with utilization of APEX in RUSVM curriculum increased from Likert mean = 2.0 to a mean of 3.9 (p =

©American Psychological Association, 2020. This paper is not the copy of record and may not exactly replicate the authoritative document published in the APA journal. Please do not copy or cite without author's permission. The final article is available, upon publication, at: https://doi.apa.org/doi/10.1037/bul0000220 To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer five original research questions related to moral judgments, negotiations, and implicit cognition. Participants from 2 separate large samples (total N 15,000) were then randomly assigned to complete 1 version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: Materials from different teams rendered statistically significant effects in opposite directions for 4 of 5 hypotheses, with the narrowest range in estimates being d = 0.37 to 0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for 2 hypotheses and a lack of support for 3 hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, whereas considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.

Based on the example of Metropolitan Cork, this paper looks at strands of planning thinking as they apply to the city-region: economic and political arguments about the scale of a city; landscape arguments about identity and place; spatial arguments about urban form and environmentally grounded arguments about nature, ecology and the city. Bringing together the different theoretical contexts and disciplinary frameworks of these interrelated approaches and relating them both to the often contradictory principles of sustainable development and to the challenge of achieving appropriate systems of governance at this scale, it explores an initial argument for how holistic and mutually reinforcing approaches to the spatial resilience of a city region might re-emerge.

Introduction This module introduces learners to the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD–10-CM) coding system and its relevance to patient care, billing, and public health. Knowledge of this coding system is critical for residents about to enter independent practice. Methods This case was developed for internal medicine residents at all levels of training and was delivered in three 50-minute sessions. Associated materials include a test given before and after the module, the answer key to that test, the clinical case and associated learning objectives, a faculty guide, and an evaluation form. This module features a simulated patient encounter in an electronic health record, the details of which are given in the faculty guide. Results Eighty-eight percent of learners reported that they found this exercise useful, and there was a significant improvement in posttest scores after completion. Ninety-four percent of learners reported a commitment to using appropriate ICD–10-CM codes in their own practice after completion of the exercise. Discussion This effective module has been integrated into our ambulatory curriculum. Knowledge of ICD–10-CM coding allows physicians to document specifically and appropriately as they move forward in their practice.

Objectives. To characterize the in vitro binding and effector function properties of CD20-directed small modular immunopharmaceutical (SMIP) 2LM20-4, and to compare its in vivo B-cell depletion activity with the mutated 2LM20-4 P331S [no in vitro complement-dependent cytotoxicity (CDC)] and rituximab in cynomolgus monkeys. Methods. Direct binding is examined in flow cytometry, confocal microscopy, scatchard and lipid raft assays. Effector function assays include CDC and Fc-mediated cellular toxicity. In the 6-month-long in vivo B-cell depletion study, single i.v. dosages of 1 or 10 mg/kg of anti-CD20 proteins were administered to monkeys and B-cell counts were monitored in peripheral blood, bone marrow and lymph nodes. Results. 2LM20-4 has lower saturation binding to human primary B cells and recruits fewer CD20 molecules into lipid rafts compared with rituximab; however, it induces higher in vitro CDC. In competitive binding, 2LM20-4 only partially displaces rituximab, suggesting that it binds to a fraction of CD20 molecules within certain locations of the plasma membrane as compared with rituximab. In monkeys, 2LM20-4 had more sustained B-cell depletion activity than rituximab in peripheral blood and had significantly more profound and sustained activity than 2LM20-4 P331S and rituximab in the lymph nodes. Conclusions. SMIP 2LM20-4, which binds to a fraction of CD20 molecules as compared with rituximab, has more potent in vitro CDC, and more potent and sustained B-cell depletion activity in cynomolgus monkeys. Our work has considerable clinical relevance since it provides novel insights related to the emerging B-cell depletion therapies in autoimmune diseases.

Targeting more than one molecule in multifactorial diseases involving several disease mediators may provide improved therapeutic efficacy. Psoriasis is a multifactorial disease in which interleukin (IL)-6 and IL-23 are important disease mediators because they facilitate development of Th17 cells; widely accepted to be associated with psoriasis. To meet the need for new therapeutics, we aimed to create a clinically relevant bispecific drug, by combining the inhibitory properties of anti-IL-6 and anti-IL-23 antibodies, exhibiting high affinity, high stability and the ability to be produced in high yield. The bispecific molecule AZ17 was created by combining high affinity binding domains originating from monoclonal antibodies targeting human IL-6 and IL-23. To allow for high and efficient production, AZ17 was assembled by site-specific bioconjugation from two individual single chain fragment variables that were synthesized separately in Escherichia coli. To improve stability and extend pharmacokinetics, a flexible poly-ethylene glycol molecule was used as linker. In preclinical psoriasis models, AZ17 reduced IL-23-induced ear inflammation and improved psoriasis in a xenograft transplantation model where psoriasis skin is transplanted onto immune-deficient mice. The data presented here suggest AZ17 to be a promising drug candidate in psoriasis and other inflammatory diseases associated with Th17 cell development.

Hypomorphic mutations in the zinc finger domain of NF-kappaB essential modulator (NEMO) cause X-linked hyper-IgM syndrome with ectodermal dysplasia (XHM-ED). Here we report that patient B cells are characterized by an absence of Ig somatic hypermutation (SHM) and defective class switch recombination (CSR) despite normal induction of activation-induced cytidine deaminase (AID) and Iepsilon-Cepsilon transcripts. This indicates that AID expression alone is insufficient to support neutralizing antibody responses. Furthermore, we show that patient B cells stimulated with CD40 ligand are impaired in both p65 and c-Rel activation, and whereas addition of IL-4 can enhance p65 activity, c-Rel activity remains deficient. This suggests that these NF-kappaB components have different activation requirements and that IL-4 can augment some but not all NEMO-dependent NF-kappaB signaling. Finally, using microarray analysis of patient B cells we identified downstream effects of impaired NF-kappaB activation and candidate factors that may be necessary for CSR and SHM in B cells.

(2001). Planning and Documenting Consultation in Adapted Physical Education. Journal of Physical Education, Recreation & Dance: Vol. 72, No. 8, pp. 49-52.

The inducible costimulator (ICOS) is the newest member of the CD28/CD152 receptor family involved in regulating T cell activation. We constructed a soluble-Ig fusion protein of the extracellular domain of human ICOS and used it as a probe to characterize expression patterns of the ICOS ligand (ICOSL). ICOSIg did not bind to CD80- or CD86-transfected Chinese hamster ovary cell lines, demonstrating that ICOSL is distinct from those ligands identified for CD28/CD152. ICOSIg showed selective binding to monocytic and B cell lines, whereas binding was undetectable on unstimulated monocytes and peripheral blood T and B cells. Expression of ICOSL was induced on monocytes after integrin-dependent plastic adhesion. Pretreatment of monocytes with mAb to the β2-integrin subunit CD18 decreased adhesion and abolished ICOSL up-regulation but had no effect on CD80/86 (CD152 ligand (CD152L)) expression. Both ICOSL and CD152L were up-regulated on monocytes by IFN-γ but by distinct signaling pathways. Unlike CD152L expression, ICOSL expression did not change when monocytes were differentiated into dendritic cells (DCs) or after DCs were induced to mature by LPS, TNF-α, or CD40 ligation. Addition of ICOSIg to allogeneic MLRs between DCs and T cells reduced T cell proliferative responses but did so less efficiently than CTLA4Ig (CD152Ig) did. Similarly, ICOSIg also blocked Ag-specific T cell proliferation to tetanus toxoid. Thus, ICOSL, like CD80/86, is expressed on activated monocytes and dendritic cells but is regulated differently and delivers distinct signals to T cells that can be specifically inhibited by ICOSIg.

Bispecific antibodies offer a promising approach for the treatment of cancer but can be challenging to engineer and manufacture. Here we report the development of PF-06671008, an extended-half-life dual-affinity re-targeting (DART®) bispecific molecule against P-cadherin and CD3 that demonstrates antibody-like properties. Using phage display, we identified anti-P-cadherin single chain Fv (scFv) that were subsequently affinity-optimized to picomolar affinity using stringent phage selection strategies, resulting in low picomolar potency in cytotoxic T lymphocyte (CTL) killing assays in the DART format. The crystal structure of this disulfide-constrained diabody shows that it forms a novel compact structure with the two antigen binding sites separated from each other by approximately 30 Å and facing approximately 90° apart. We show here that introduction of the human Fc domain in PF-06671008 has produced a molecule with an extended half-life (-4.4 days in human FcRn knock-in mice), high stability (Tm1 > 68 °C), high expression (>1 g/L), and robust purification properties (highly pure heterodimer), all with minimal impact on potency. Finally, we demonstrate in vivo anti-tumor efficacy in a human colorectal/human peripheral blood mononuclear cell (PBMC) co-mix xenograft mouse model. These results suggest PF-06671008 is a promising new bispecific for the treatment of patients with solid tumors expressing P-cadherin.

Malnutrition is a common problem in head and neck cancer with up to 50% of the patients developing some degree of nutritional deficiency.1 The etiologies of this problem can be divided into two categories: tumor related or treatment related. Patient with tumor related malnutrition typically present with obvious clinical signs and symptoms of undernourishment. Tumor cachexia can contribute but this is primarily caused by physical impediments to oral consumption such as pain, oropharygeal obstruction, or nerve compression , all resulting in discordant degluttination.2 Prior to definitive cancer therapy, this group of patients requires nutritional resuscitation. Additionally many patients who present nutritionally sound and who undergo surgical resection experience some degree of postoperative nutritional difficulties. In many cases it a short lived and inconsequential. However, a subset of patients will experience a more severe prolonged course requiring enteral supplementation. Prior studies have shown that if these patients are not supplemented, they will likely experience severe dehydration, treatment intolerance, or severe treatment related complications that require hospitalization.3,4 Inherently, the surgical treatment of head and neck malignancies can be quite debilitating and result in significant mastication and deglutination dysfunction.5-7 At times this involves radical resections that require complex reconstructions to maintain oropharyngeal continuity; and adjuvant radiation and/or chemotherapy may be required to maximize local control. Indiscriminately placing PEG tubes in all patients would put many patients at risk for PEG related complications.8-13 Therefore, the difficulty has been trying to preoperatively identify which patients likely to experience prolonged treatment induced malnutrition and benefit from early nutritional supplementation. Groups have identified some factors that are predictive of a need for enteral support.3,4,14-17 One factor that has been clearly established is radiation therapy, particular when given

HIPAA security compliance in academic medical centers is a central concern of researchers, academicians, and practitioners. Despite increasing accounts of data security breaches, greater numbers of information technology implementations, and new HIPAA Security Rule requirements and audits, academic medical centers have shown limited HIPAA security compliance. Based on a literature review of technology acceptance and security effectiveness, this study investigated the factors that affect HIPAA security compliance. A theoretical model using management support, security awareness, security culture, and computer self-efficacy to predict security behavior and security effectiveness was proposed. Multiple linear regression and correlation analysis demonstrated that security awareness, management support, and security culture were significant predictors of security effectiveness and security behavior, with security awareness being the most significant predictor. The results of this research provide guidance to those involved with HIPAA security compliance initiatives in health care.

Interaction of the B7 molecule on antigen-presenting cells with its receptors CD28 and CTLA-4 on T cells provides costimulatory signals for T cell activation. We have studied the effects of B7 on antitumor immunity to a murine melanoma that expresses a rejection antigen associated with the E7 gene product of human papillomavirus 16. While this E7+ tumor grows progressively in immunocompetent hosts, cotransfection of its cells with B7 led to tumor regression by a B7-dependent immune response mediated by CD8+ cytolytic T lymphocytes. The immune response induced by E7+B7+ tumor cells also caused regression of E7+B7- tumors at distant sites and was curative for established E7+B7- micrometastases. Our findings suggest that increasing T cell costimulation through the CD28 and CTLA-4 receptors may have therapeutic usefulness for generating immunity against tumors expressing viral antigens.

An intensive behavior management plan that employs the use of picture discrimination boards, adaptive sexual equipment, and sexual education/sexual function training for the resident and staff is described. The purpose is to aid a 74-year-old male with severe to moderate mental retardation, living in a residential facility to masturbate safely and appropriately. Baseline data was collected to determine the frequency of the potentially self-injurious behavior, which was the insertion of various objects into his rectum. Results indicated a significant reduction in potentially injurious masturbation.