Safe at home: Acceptance of surveillance technology among caregivers for persons with dementia.

The increasing incidence of dementia calls for effective and innovative approaches to alleviate societal and personal burdens. Aging in place is a sustainable paradigm which ensures the best utilization of societal resources, supports caregivers, secures normalcy, and optimizes care for persons with dementia (PwD). Home-based surveillance technology can support PwD in safely aging in place. This study examines factors associated with the adoption of home-based surveillance technologies among unpaid dementia caregivers. Through an online survey (N = 203), we apply ordinal logistic regression to identify five variables that predict the likelihood of caregivers' surveillance technology adoption for dementia care. The predictors are caregivers': (1) trouble concerns about PwD, (2) online support group membership, (3) perceived social norms regarding surveillance technology use, (4) perceived usefulness of surveillance devices, and (5) depth of information and communication technologies (ICT) use. Theoretical and practical implications for dementia healthcare are discussed.

Moralization of E-cigarette Use and Regulation: A Mixed-Method Computational Analysis of Opinion Polarization.

E-cigarette use, or vaping, is undergoing a process of moralization in which issues about vaping evolve from being morally neutral to having discernible moral implications. Using Moral Foundations Theory, this study compared the moral narratives underlying polarized views about e-cigarette use and regulation. We integrated computational and human strategies by conducting the Chow test on the time series data and classification, topic modeling, and Chi-square tests on posts (N = 2,669) from 26 pro-vaping and 19 anti-vaping Facebook Pages. The observation period (August 1, 2019 to March 5, 2020) encompassed the outbreak of "e-cigarette or vaping product use associated lung injury" (EVALI), deaths and subsequent legislation. Results revealed that pro-vaping posts were more likely than anti-vaping posts to mention Fairness/cheating and Authority/subversion, involving a conspiracy belief in an "e-cigarettes vs. Big Tobacco" rivalry, while anti-vaping posts were more likely to mention Sanctity/degradation. There were no significant differences between pro-vaping and anti-vaping posts in the likelihood of mentioning Care/harm or Loyalty/betrayal. Nevertheless, according to the topic modeling results, the use of moral foundations varied between pro-vaping and anti-vaping narratives, with the meanings of Care/harm and Loyalty/betrayal dependent on the post author's group affiliation. Health interventions can tailor persuasive messages to different moral values and debunk misinformation about public health policies to mitigate the vaping epidemic. Theoretical implications are also discussed.

The Development and Testing of the MISSCARE Survey OR.

BACKGROUND: An acceptable, reliable, and valid survey instrument to measure missed nursing care in perioperative settings has not been developed. PURPOSE: To develop and conduct psychometric testing of the MISSCARE Survey OR. METHODS: Data were collected nationwide from 1,693 operating room (OR) nurses who completed the MISSCARE Survey OR. The survey contained two sections: Part A, "Elements of perioperative nursing care" (32 questions) and Part B, "Reasons for missing nursing care" (17 questions). RESULTS: The MISSCARE Survey OR demonstrated acceptability, as few respondents missed questions in Part A (0.1%-1.1%) and Part B (0.8%-1.3%). Exploratory factor analysis revealed five subscales in Part A (Legal, Preparation, Safety, Communication, and Closing) and four in Part B (Urgency, Staffing, Materials, and Teamwork). In Part A, the five-factor solution explained 44% of the variance. In Part B, the four-factor solution explained 53% of the variance. Alpha coefficients for subscales in Part A ranged from 0.71 to 0.84 and 0.74 to 0.90 for Part B. Validity was measured using content validity, criterion validity, and construct validity. A panel of OR nurse experts established content validity. Criterion validity compared hospitals with fewer than six ORs to hospitals with hospitals with more than six ORs where it was hypothesized aprior that nurses in hospitals with fewer ORs would have missed less care (X = -.123, standard error [SE] = .041, p = .003). Construct validity was tested through exploratory and confirmatory factor analyses (CFA). Correlation coefficients for Part A ranged from 0.34 to 0.73 and 0.60 to 0.73 for Part B. Overall model fit was acceptable: goodness-of-fit index (GFI) and CFA were greater than 0.90, standardized root mean square residual (SMRM) was less than 0.06, and root mean square error of approximation (RMSEA) less than 0.08. CONCLUSION: The MISSCARE Survey OR promises to be a reliable, valid indicator of the extent of and reasons for missed nursing care.

Phase 1 study of single-agent WNT974, a first-in-class Porcupine inhibitor, in patients with advanced solid tumours.

BACKGROUND: This Phase 1 study assessed the safety and efficacy of the Porcupine inhibitor, WNT974, in patients with advanced solid tumours. METHODS: Patients (n = 94) received oral WNT974 at doses of 5-30 mg once-daily, plus additional dosing schedules. RESULTS: The maximum tolerated dose was not established; the recommended dose for expansion was 10 mg once-daily. Dysgeusia was the most common adverse event (50% of patients), likely resulting from on-target Wnt pathway inhibition. No responses were seen by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; 16% of patients had stable disease (median duration 19.9 weeks). AXIN2 expression by RT-PCR was reduced in 94% of paired skin biopsies (n = 52) and 74% of paired tumour biopsies (n = 35), confirming inhibition of the Wnt pathway. In an exploratory analysis, an inverse association was observed between AXIN2 change and immune signature change in paired tumour samples (n = 8). CONCLUSIONS: Single-agent WNT974 treatment was generally well tolerated. Biomarker analyses suggest that WNT974 may influence immune cell recruitment to tumours, and may enhance checkpoint inhibitor activity. CLINICAL TRIAL REGISTRATION: NCT01351103.

PCA062, a P-cadherin Targeting Antibody-Drug Conjugate, Displays Potent Antitumor Activity Against P-cadherin-expressing Malignancies.

The cell surface glycoprotein P-cadherin is highly expressed in a number of malignancies, including those arising in the epithelium of the bladder, breast, esophagus, lung, and upper aerodigestive system. PCA062 is a P-cadherin specific antibody-drug conjugate that utilizes the clinically validated SMCC-DM1 linker payload to mediate potent cytotoxicity in cell lines expressing high levels of P-cadherin in vitro, while displaying no specific activity in P-cadherin-negative cell lines. High cell surface P-cadherin is necessary, but not sufficient, to mediate PCA062 cytotoxicity. In vivo, PCA062 demonstrated high serum stability and a potent ability to induce mitotic arrest. In addition, PCA062 was efficacious in clinically relevant models of P-cadherin-expressing cancers, including breast, esophageal, and head and neck. Preclinical non-human primate toxicology studies demonstrated a favorable safety profile that supports clinical development. Genome-wide CRISPR screens reveal that expression of the multidrug-resistant gene ABCC1 and the lysosomal transporter SLC46A3 differentially impact tumor cell sensitivity to PCA062. The preclinical data presented here suggest that PCA062 may have clinical value for treating patients with multiple cancer types including basal-like breast cancer.

The Effect of RN Circulator-Scrub Person Dyad Consistency on Total OR Time and Turnover Time.

Operating room efficiency is an important consideration for perioperative nurse leaders because it can affect their facilities' revenue and provider and patient satisfaction. Using consistent perioperative teams, including the same RN circulator and scrub person, for consecutive procedures may improve OR efficiency. This retrospective cross-sectional cohort study assessed the effects of a consistent team in the form of RN circulator-scrub person dyads on the total OR and turnover times for 310 surgical procedures using electronic OR records data from the National Surgical Quality Improvement Program that was collected in 2008. Controlling for relevant variables (eg, procedure type consistency, number of staff members present, procedure complexity), the association between RN circulator-scrub person dyads and total OR time and turnover time was not significant.

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms.

SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor immunity, including enhancing T cell cytotoxic function and immune-mediated tumor regression. Knockout of SHP2 using CRISPR/Cas9 gene editing showed that targeting SHP2 in cancer cells contributes to this immune response. Inhibition of SHP2 activity augmented tumor intrinsic IFNγ signaling resulting in enhanced chemoattractant cytokine release and cytotoxic T cell recruitment, as well as increased expression of MHC Class I and PD-L1 on the cancer cell surface. Furthermore, SHP2 inhibition diminished the differentiation and inhibitory function of immune suppressive myeloid cells in the tumor microenvironment. SHP2 inhibition enhanced responses to anti-PD-1 blockade in syngeneic mouse models. Overall, our study reveals novel functions of SHP2 in tumor immunity and proposes that targeting SHP2 is a promising strategy for cancer immunotherapy.

Nurses' Perceptions of the Extent and Type of Missed Perioperative Nursing Care.

Missed nursing care is a concern on inpatient hospital units but has not been adequately explored in the perioperative setting. This cross-sectional study used results from a survey of 1,693 AORN members to investigate the amount and type of missed perioperative nursing care and evaluate associations between reported missed care and facility and nurse characteristics. The survey asked OR nurses how frequently specific care items were missed by themselves or others. Overall, nurses' perceptions of the frequency of missed care was 0.84 on a scale of 0 to 4 (0 = never, 4 = always). The survey items were categorized into five subscales: legal requirement, preparation, safety, communication, and closing routine. Nurses reported most missed care in the communication and preparation categories. The number of ORs at a facility, nurse education and job title, and perceptions of staffing adequacy were significantly associated with the perceived amount of missed perioperative nursing care.

A Proof of Concept for Biomarker-Guided Targeted Therapy against Ovarian Cancer Based on Patient-Derived Tumor Xenografts.

Advanced ovarian cancers are a leading cause of cancer-related death in women and are currently treated with surgery and chemotherapy. This standard of care is often temporarily successful but exhibits a high rate of relapse, after which, treatment options are few. Here we investigate whether biomarker-guided use of multiple targeted therapies, including small molecules and antibody-drug conjugates, is a viable alternative. A panel of patient-derived ovarian cancer xenografts (PDX), similar in genetics and chemotherapy responsiveness to human tumors, was exposed to 21 monotherapies and combination therapies. Three monotherapies and one combination were found to be active in different subsets of PDX. Analysis of gene expression data identified biomarkers associated with responsiveness to each of the three targeted therapies, none of which directly inhibits an oncogenic driver. While no single treatment had as high a response rate as chemotherapy, nearly 90% of PDXs were eligible for and responded to at least one biomarker-guided treatment, including tumors resistant to standard chemotherapy. The distribution of biomarker positivity in The Cancer Genome Atlas data suggests the potential for a similar precision approach in human patients. SIGNIFICANCE: This study exploits a panel of patient-derived xenografts to demonstrate that most ovarian tumors can be matched to effective biomarker-guided treatments.

Social Media Propagation of Content Promoting Risky Health Behavior.

While social media have been found useful in providing social support and health information, they have also been home to content advocating risky health behavior. This study focused on how content defending and even celebrating anorexia as a lifestyle are circulated among social media users, and investigates the characteristics that promote wide propagation of such messages. We captured anorexia-related content on Tumblr, a popular blog for talking about eating disorders, during a one-month period. Among the 35,432 posts collected, we examined the most highly propagated posts and coded them for message characteristics. Our findings revealed that posts in which the source of a narrative ("testimony") was identified (was either from an anorexic poster or about another's anorexia) and which were positive toward the pro-anorexia perspective were more likely to be propagated on Tumblr. In addition, posts containing content that references an anorexic person and contains an affective tone were more likely to be propagated. We also found that underweight bodies and bodies with a high degree of exposure were associated with propagation of posts. The present study suggested practical implications by focusing on the characteristics of highly propagated but potentially harmful content in social media.

Complete nucleotide sequence of clematis chlorotic mottle virus, a new member of the family Tombusviridae.

Clematis chlorotic mottle virus (ClCMV) is a previously undescribed virus associated with symptoms of yellow mottling and veining, chlorotic ring spots, line pattern mosaics, and flower distortion and discoloration on ornamental Clematis. The ClCMV genome is 3,880 nt in length with five open reading frames (ORFs) encoding a 27-kDa protein (ORF 1), an 87-kDa replicase protein (ORF 2), two centrally located movement proteins (ORF 3 and 4), and a 37-kDa capsid protein (ORF 5). Based on morphological, genomic, and phylogenetic analysis, ClCMV is predicted to be a member of the genus Pelarspovirus in the family Tombusviridae.

Enhanced targeting of CML stem and progenitor cells by inhibition of porcupine acyltransferase in combination with TKI.

Tyrosine kinase inhibitor (TKI) treatment of chronic myeloid leukemia (CML) has limited efficacy against leukemia stem cells (LSC) responsible for disease propagation, and most CML patients require continued TKI treatment to maintain remission. LSC maintenance is related, at least in part, to signals from the bone marrow microenvironment (BMM). Our previous studies have shown that Wnt signaling from the BMM contributes to preservation of CML LSC following TKI treatment. Secretion of Wnt ligands requires their modification by the O-acyl transferase Porcupine (PORCN). Here we investigated the activity of a potent and selective PORCN inhibitor, WNT974, against CML stem and progenitor cells. WNT974 efficiently antagonized Wnt signaling in human CML CD34+ cells, and in combination with the TKI nilotinib (NIL) significantly enhanced inhibition of proliferation and colony-forming potential of CML stem and progenitor cells and reduced their growth in immunodeficient mice in vivo, in comparison with NIL alone. Treatment of transgenic CML mice in vivo with NIL in combination with WNT974 significantly reduced leukemic stem and progenitor cell numbers, reduced regeneration of leukemic long-term hematopoietic stem cells in secondary transplant recipients, and enhanced survival of mice after discontinuation of treatment, in comparison with NIL alone. CML progenitors demonstrated enhanced sensitivity to Wnt stimulation, associated with increased expression of the FZD4 receptor. FZD4 knockdown inhibited CML progenitor growth. These results support further investigation of PORCN targeting to inhibit Wnt secretion and signaling and enhance targeting of CML stem cells while sparing their normal counterparts.

Exploring Willingness to Participate in Clinical Trials by Ethnicity.

African-Americans and Hispanic-Americans are disproportionately affected by cancer, yet underrepresented in cancer clinical trials. Because of this, it is important to understand how attitudes and beliefs about clinical trials vary by ethnicity. A national, random sample of 860 adults was given an online survey about attitudes toward clinical trials. We examined willingness to participate in clinical trials, attitudes toward clinical trials, trust in doctors, attitudes toward alternative and complementary medicine, and preferred information channels. Results indicate that African-American and Hispanic-American participants have more negative attitudes about clinical trials, more distrust toward doctors, more interest in complementary and alternative medicine, and less willingness to participate in clinical trials than white/non-Hispanics, although specific factors affecting willingness to participate vary. The channels people turn to for information on clinical trials also varied by ethnicity. These results help explain the ethnic disparities in cancer clinical trial enrollment by highlighting some potential underlying causes and drawing attention to areas of importance to these groups.

A Comparison Between Caucasians and African Americans in Willingness to Participate in Cancer Clinical Trials: The Roles of Knowledge, Distrust, Information Sources, and Religiosity.

This study aims to (a) examine the roles of knowledge, distrust in medical professionals, information sources, and 2 dimensions of religiosity (i.e., religious activity and religious belief) in influencing willingness to participate (WTP) in cancer clinical trials and to (b) compare the results for Caucasians and African Americans in order to inform future recruitment. An online survey was fielded via a Knowledge Networks panel with a nationally representative sample including 478 Caucasians and 173 African Americans. The results showed that distrust in medical professionals was a strong barrier to WTP for both ethnic groups, whereas factual knowledge about trial procedures was not associated with WTP for either ethnic group. Seeking trial information from doctors was positively associated with WTP for Caucasians; seeking trial information from hospitals was positively associated with WTP for African Americans. More interestingly, levels of religious activity negatively predicted WTP for Caucasians but positively predicted WTP for African Americans. Self-reported religious belief was not associated with WTP for either ethnic group. In sum, although distrust is a common barrier to WTP, the influence of preferred information sources and religious activity on WTP varies as a function of ethnicity.

Propagation of Information About Preexposure Prophylaxis (PrEP) for HIV Prevention Through Twitter.

Previous literature has suggested that examining Twitter messages can be productive for studying how the public shares and spreads health information on social media. Preexposure prophylaxis (PrEP) is a promising approach to HIV prevention, yet there are many issues that may influence its effective implementation. This study examined social representations of PrEP on Twitter. One thousand four hundred and thirty-five Tweets were collected and 774 English Tweets were content-analyzed to explore propagation of various issues around daily oral PrEP, as well as characteristics of the sources of those Tweets. We also examined how Twitter message content influenced information propagation. Our findings revealed that PrEP-related information on Twitter covered a wide range of issues, and individual users constituted the majority of the Tweet creators among all the sources, including news media, nonprofit and academic groups, and commercial entities. Using Poisson regression, we also found that a Tweet's affective tone was a significant predictor of message propagation frequency. Implications for health practitioners are discussed.

High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.

Profiling candidate therapeutics with limited cancer models during preclinical development hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous patient responses for patient-selection strategies. We established ∼1,000 patient-derived tumor xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, we performed in vivo compound screens using a 1 × 1 × 1 experimental design (PDX clinical trial or PCT) to assess the population responses to 62 treatments across six indications. We demonstrate both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. In addition, our results suggest that PCTs may represent a more accurate approach than cell line models for assessing the clinical potential of some therapeutic modalities. We therefore propose that this experimental paradigm could potentially improve preclinical evaluation of treatment modalities and enhance our ability to predict clinical trial responses.

Relationship between operating room nursing staff expertise and patient outcomes.

This secondary analysis evaluated the association of operating room scrub staff expertise, based on frequency of working on a specific surgical procedure, with the development of surgical site infections. The odds of developing surgical site infections decreased by 5.7% (odds ratio = 0.943; 95% confidence interval, 0.834-1.067) with increased expertise, although a statistically significant association was not established (P = .354). The relationship between operating room scrub staff expertise and patient outcomes is important to understand.

An intervention to improve nursing teamwork using virtual simulation.

The purpose of this study was to test the use of virtual simulation to improve teamwork among nursing staff. Using a quasi-experimental design, nursing staff (n = 43) from one patient care unit participated in a 1-hr session, which focused on common nursing teamwork problems. The overall mean teamwork scores improved from pre- (M = 3.25, SD = 0.58) to post-intervention (M = 3.49, SD = 0.67, p < .012). The intervention also had large (0.60 ≤ d ≤ 0.97) and significant effects on the measures of three teamwork subscales (i.e., trust, team orientation, and backup).

The Quality, Implementation, and Evaluation Model: A Clinical Practice Model for Sustainable Interventions.

Major efforts have been directed toward the implementation of sustainable quality improvement. To date, progress has been noted using various metrics and performance measures; however, successful implementation has proven challenging. The Quality, Implementation, and Evaluation (QIE) model, derived from Donabedian's structure component, presents a framework for implementation of specific activities. The QIE model consists of Policy, Patient Preparedness, Provider Competency, and Performance and Accountability, to guide specific practice initiatives. The implementation of alcohol-based pre-operative skin prep was evaluated in a sample of 17 hospitals and demonstrated that hospitals actively engaged in the components of the model demonstrated a significantly higher use of alcohol-based skin preparation agent than hospitals that did not engage in QIE model activities. The QIE model presents a powerful and actionable implementation model for mid-level management and clinical leadership. Future studies will further evaluate the impact of the specific components of the QIE model.