On What Grounds? A Pilot Study of References Used in Clinical Ethics Consultation and Education.

In accordance with standards published by the American Society for Bioethics and Humanities (ASBH), ethics consultants are expected to provide recommendations that align with scholarly literature, professional society statements, law, and policy. However, there are no studies to date that characterize the specific references that ethics consultants and educators use to inform their work. To address this gap, a convenience sample of clinical ethics consultants and educators was surveyed online through two major listservs for clinical ethics, the ASBH Clinical Ethics Consultation Affinity Group (CECAG) and the Association of Bioethics Program Directors (ABPD). Ninety-five ethics consultants and/or educators with diverse educational background, credentials, and experience provided responses. In total, 451 references, 315 of which were unique, were reported. These references were broken into 6 categories after analysis: bioethics literature (divided into articles and books), professional society documents (divided into professional society statements and codes of ethics), federal/state/uniform/case law, hospital/health system policies, official religious teachings, and other. We found extensive variation and minimal overlap in the references respondents used for ethics consultation and education, even when referring to the same topics. Future research directions should include conducting more systematic efforts to characterize the references used by ethics consultants across the US; determining whether demographic characteristics of consultants influence the references used; and ascertaining whether the variation in references used reflects genuine disagreements in consultants' and educators' bioethical analysis or recommendations.

Three-Dimensional Epitaxy of Low-Defect 3C-SiC on a Geometrically Modified Silicon Substrate.

We demonstrate the growth of 3C-SiC with reduced planar defects on a micro-scale compliant substrate. Heteroepitaxial growth of 3C-SiC on trenches with a width and separation of 2 µm, etched into a Si(001) substrate, is found to suppress defect propagation through the epilayer. Stacking faults and other planar defects are channeled away from the center of the patterned structures, which are rounded through the use of H2 annealing at 1100 °C. Void formation between the columns of 3C-SiC growth acts as a termination point for defects, and coalescence of these columns into a continuous epilayer is promoted through the addition of HCl in the growth phase. The process of fabricating these compliant substrates utilizes standard processing techniques found within the semiconductor industry and is independent of the substrate orientation and offcut.

A mixed methods evaluation assessing the feasibility of implementing a PrEP data dashboard in the Southeastern United States.

BACKGROUND: Alabama is one of seven priority states for the National Ending the HIV Epidemic Initiative due to a disproportionate burden of rural infections. To reverse growing infection rates, the state must increase its focus on prevention efforts, including novel strategies. One such approach is to utilize dashboards that visualize real-time data on the pre-exposure prophylaxis (PrEP) care continuum to assist in prioritizing evidence-based preventative care for those most vulnerable for HIV infection. METHODS: We conducted a mixed methods evaluation to ascertain stakeholders' perceptions on the acceptability, feasibility, appropriateness, and usability of a PrEP care continuum dashboard, as well as gain insight on ways to improve the activities necessary to sustain it. Clinicians, administrators, and data personnel from participating sites in Alabama completed surveys (n = 9) and participated in key informant interviews (n = 10) to better understand their experiences with the prototype data dashboard and to share feedback on how it can be modified to best fit their needs. RESULTS: Surveys and interviews revealed that all participants find the pilot data dashboard to be an acceptable, feasible, and appropriate intervention for clinic use. Overall, stakeholders find the pilot dashboard to be usable and helpful in administrative efforts, such as report and grant writing; however, additional refining is needed in order to reduce burden and optimize usefulness. Participants voiced concerns about their site's abilities to sustain the dashboard, including the lack of systematized PrEP protocols and limited funds and staff time dedicated to PrEP data collection, cleaning, and upload. CONCLUSION: Study participants from clinics providing HIV prevention services, including PrEP, in Alabama voiced interest in sustaining and refining a data dashboard that tracks clients across the PrEP care continuum. Despite viewing the platform itself as an acceptable, feasible, and appropriate intervention, participants agreed that efforts need to be focused on standardizing PrEP data collection protocols in order to ensure consistent, accurate data capture and that limited funds and staff time are barriers to the sustained implementation of the dashboard in practice.

Organizational Ethics in Healthcare: A National Survey.

Organizational ethics-defined as the alignment of an institution's practices with its mission, vision, and values-is a growing field in health care not well characterized in empirical literature. To capture the scope and context of organizational ethics work in United States healthcare institutions, we conducted a nationwide convenience survey of ethicists regarding the scope of organizational ethics work, common challenges faced, and the organizational context in which this work is done. In this article, we report substantial variability in the structure of organizational ethics programs and the settings in which it is conducted. Notable findings included disagreement about the activities that comprise organizational ethics and a lack of common metrics used to assess organizational ethics activities. A frequently cited barrier to full engagement in these activities was poor institution-wide understanding about the role and function of organizational ethics resources. These data suggest a tension in the trajectory of organizational ethics' professionalization: while some variability is appropriate to the field's relative youth, inadequate attention to definitions of organizational ethics practice and metrics for success can impede discussions about appropriate institutional support, leadership context, and training for practitioners.

Bioethics in Gerontology: Developing a Typology of Ethical Issues in Assisted Living.

Assisted living (AL) simultaneously is home to older adults who cannot live independently and a place where people work and visit and, therefore, where value conflicts are apt to arise. In this report we present the "Typology of Ethical Issues in Assisted Living" with emphasis on its development. The typology derives from a synthesis of frameworks used in acute care spaces adapted and applied to data collected as part of an ethnographic study involving AL residents with dementia. Our work advances knowledge and has implications for future research and practice.

The Hedgehog Pathway as a Therapeutic Target in Chronic Myeloid Leukemia.

Despite the development of therapeutic agents that selectively target cancer cells, relapse driven by acquired drug resistance and resulting treatment failure remains a significant issue. The highly conserved Hedgehog (HH) signaling pathway performs multiple roles in both development and tissue homeostasis, and its aberrant regulation is known to drive the pathogenesis of numerous human malignancies. However, the role of HH signaling in mediating disease progression and drug resistance remains unclear. This is especially true for myeloid malignancies. The HH pathway, and in particular the protein Smoothened (SMO), has been shown to be essential for regulating stem cell fate in chronic myeloid leukemia (CML). Evidence suggests that HH pathway activity is critical for maintaining the drug-resistant properties and survival of CML leukemic stem cells (LSCs), and that dual inhibition of BCR-ABL1 and SMO may comprise an effective therapeutic strategy for the eradication of these cells in patients. This review will explore the evolutionary origins of HH signaling, highlighting its roles in development and disease, which are mediated by canonical and non-canonical HH signaling. Development of small molecule inhibitors of HH signaling and clinical trials using these inhibitors as therapeutic agents in cancer and their potential resistance mechanisms, are also discussed, with a focus on CML.

Role of Visit Modality in the HIV-Related No-Shows During the COVID-19 Pandemic: A Multisite Retrospective Cohort Study.

The emergence of the COVID-19 pandemic necessitated rapid expansion of telehealth as part of healthcare delivery. This study compared HIV-related no-shows by visit type (in-person; video; telephone) during the COVID-19 pandemic (April 2020-September 2021) from the Data for Care Alabama project. Using all primary care provider visits, each visit's outcome was categorized as no-show or arrived. A logistic regression model using generalized estimating equations accounting for repeat measures in individuals and within sites calculated odds ratios (OR) and their accompanying 95% confidence interval (CI) for no-shows by visit modality. The multivariable models adjusted for sociodemographic factors. In-person versus telephone visits [OR (95% CI) 1.64 (1.48-1.82)] and in-person versus video visits [OR (95% CI) 1.53 (1.25-1.85)] had higher odds of being a no-show. In-person versus telephone and video no-shows were significantly higher. This may suggest success of telehealth visits as a method for HIV care delivery even beyond COVID-19.

Assessing the Impact of COVID-19 on Retention in HIV Primary Care: A Longitudinal Multisite Analysis.

We compared retention in care outcomes between a pre-COVID-19 (Apr19-Mar20) and an early-COVID-19 (Apr20-Mar21) period to determine whether the pandemic had a significant impact on these outcomes and assessed the role of patient sociodemographics in both periods in individuals enrolled in the Data for Care Alabama project (n = 6461). Using scheduled HIV primary care provider visits, we calculated a kept-visit measure and a missed-visit measure and compared them among the pre-COVID-19 and early-COVID-19 periods. We used logistic regression models to calculated odds ratios (OR) and accompanying 95% confidence intervals (CI). Overall, individuals had lowers odds of high visit constancy [OR (95% CI): 0.85 (0.79, 0.92)] and higher odds of no-shows [OR (95% CI): 1.27 (1.19, 1.35)] during the early-COVID-19 period. Compared to white patients, Black patients were more likely to miss an appointment and transgender people versus cisgender women had lower visit constancy in the early-COVID-19 period.

Impact of variation in practice in the prenatal reporting of variants of uncertain significance by commercial laboratories: Need for greater adherence to published guidelines.

OBJECTIVE: To evaluate the impact of implementing commercial whole exome sequencing (WES) and targeted gene panel testing in pregnancies with fetal anomalies. METHODS: A retrospective chart review of 124 patients with sequencing performed by commercial laboratories. RESULTS: The diagnostic yield of WES and panel testing was 21.5% and 26%, respectively, based on likely pathogenic (LP) or pathogenic (P) variants. Forty-two percent of exomes and 32% of panels analysed had one or more variants of uncertain significance (VUS) reported. A multidisciplinary in-depth review of the fetal phenotype, disease phenotype, variant data, and, in some patients, additional prenatal or postnatal investigations increased the diagnostic yield by 5% for exome analysis and 6% for panel analysis. CONCLUSIONS: The diagnostic yield of WES and panel testing combined was 23% based on LP and P variants. Although the reporting of VUS contributed to a 5% increase in diagnostic yield for WES and 6% for panels, the large number of VUS reported by commercial laboratories has significant resource implications. Our results support the need for greater adherence to the recommendations on the prenatal reporting of VUS and the importance of a multidisciplinary approach that brings together clinical and laboratory expertise in prenatal genetics and genomics.

Where Are We Headed? Diagnosing Abnormal Head Shapes Through Virtual Care Visits.

PURPOSE: Since the beginning of the coronavirus disease 2019 pandemic in early March, there has been a push to expand virtual patient care visits instead of in-person clinic visits. Studies have found that telemedicine can provide efficient triaging, reduction in emergency room visits, and conservation of health care resources and personnel. Although virtual patient care has been implicated in providing similar outcomes to traditional face-to-face care in patients affected with coronavirus disease 2019, there are a lack of studies on the effectiveness of virtual care visits (VCVs) for patients with craniosynostosis or deformational plagiocephaly. This study aims to develop an understanding of whether physicians can accurately diagnose pediatric patients with craniosynostosis or deformational plagiocephaly via VCVs, and whether they can determine if affected patients will benefit from helmet correction or if surgical treatment is required. METHODS: An Institutional Review Board-approved retrospective chart analysis over a 4-month period (March 1, 2020 to June 30, 2020) was performed analyzing all pediatric patients (<18 years old) who underwent virtual care calls for diagnosis and treatment of abnormal head shape. Patients were referred to UT Physicians Pediatric Surgery clinic for evaluation by a member of the Texas Cleft-Craniofacial Team (2 surgeons or 1 physician's assistant). Variables such as patient demographics, diagnosis, and need for confirmation were pulled and recorded from Allscripts Electronic Medical Records software. RESULTS: Thirty-five patients were identified who fit our search criteria. Out of these patients, eleven (31.43%) cases were diagnosed with craniosynostosis, twenty-two (62.86%) cases were diagnosed with deformational plagiocephaly, and 2 (5.71%) cases were diagnosed as being normocephalic. Median age at virtual care evaluation was 14.10 months (Interquartile Range [IQR] 5.729, 27.542) for patients diagnosed with craniosynostosis and 6.51 months (IQR 4.669, 7.068) for patients diagnosed with deformational plagiocephaly. All eleven (100%) patients diagnosed with craniosynostosis were referred for a confirmatory computed tomography scan before undergoing surgical intervention and saw an alleviation in head shape postoperatively. Eighteen (81.82%) of patients diagnosed with deformational plagiocephaly were recommended to undergo conservative treatment and the remaining 4 (18.18%) were recommended for helmet therapy. Two cases were unable to be diagnosed virtually. These patients needed a follow-up visit in person to establish a diagnosis and plan of treatment. CONCLUSIONS: Virtual care visits are increasing in frequency and this includes consultations for abnormal head shapes. Our experience demonstrates that the majority of patients can be evaluated safely in this modality, with only 5.71% requiring additional imaging or in-person visits to confirm the diagnosis. Our study underscores the feasibility of virtually diagnosing and recommending a plan for treatment in pediatric patients with abnormal head shapes. This information can be implemented to further our knowledge on the accuracy of diagnosis and treatment options for patients with craniosynostosis and deformational plagiocephaly. Further analyses are needed to quantify the financial and patient-reported outcomes of VCVs for these patients.

Evidence-Based Recommendations for Nurse Monitoring and Management of Immunotherapy-Induced Cytokine Release Syndrome: A Systematic Review from the Children's Oncology Group.

Children with B-precursor acute lymphoblastic leukemia and B-cell lymphoma, particularly those with relapsed or refractory disease, are increasingly enrolled on phase II and phase III clinical trials studying immunotherapies. These therapeutic agents may be associated with a high risk of cytokine release syndrome (CRS), and nurses lack standardized guidelines for monitoring and managing patients with CRS. Six studies and one clinical practice guideline were included in this systematic review that examined the evidence of CRS following administration of chimeric antigen receptor T-cell therapy or the bi-specific T-cell engager antibody, blinatumomab. Six nursing practice recommendations (five strong, one weak) were developed based on low or very low-quality evidence: three reflect preinfusion monitoring, one focuses on monitoring during and postinfusion, and three pertain to the nurse's role in CRS management.

The SARS-CoV-2 pandemic is associated with increased severity of presentation of childhood onset type 1 diabetes mellitus: A multi-centre study of the first COVID-19 wave.

OBJECTIVE: Children are usually mildly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19). However, the pandemic has caused collateral damage to those with non-COVID-19 diseases. We aimed to determine the impact of the COVID-19 pandemic on the presentation of newly diagnosed childhood onset type 1 diabetes. METHODS: This was a cross-sectional study conducted over a 1-year period. We compared the severity of presentation of new-onset type 1 diabetes in children under the age of 18 presenting to the multi-centre North Central London diabetes network before (1 July 2019 to 22 March 2020) and during (23 March 2020 to 30 June 2020) the first wave of the COVID-19 pandemic in the United Kingdom. RESULTS: Over the 1-year study period, a total of 30 children presented with new-onset type 1 diabetes during the pre-pandemic period and 17 presented during the first COVID-19 wave. Children presented more frequently in diabetic ketoacidosis (DKA) during the first COVID-19 wave compared with pre-pandemic (pre-pandemic: mild 13%, moderate 6.7%, severe 10%; first COVID-19 wave: mild 5.9%, moderate 24%, severe 47%; p = 0.002). During the first COVID-19 wave, DKA presentations in children with a family history of type 1 diabetes were fewer compared to those without a family history (33.3% vs. 100.0%; p = 0.006). Children presenting in severe DKA pre-pandemic were younger than those not in severe DKA (3.9 years vs. 12.2 years, p < 0.001) but this difference was not significant during the first COVID-19 wave (10.1 years vs. 11.2 years, p = 0.568). Presenting HbA1c measurement was higher in those presenting during the first COVID-19 wave (13.0 ± 1.7 vs. 10.4 ± 3.2%; 119 ± 19 vs. 90 ± 35 mmol/mol; p = 0.008). CONCLUSION: The COVID-19 pandemic is associated with increased severity of presentation of childhood onset type 1 diabetes. Whatever the context, young people with suspected new-onset type 1 diabetes should be referred for urgent clinical review.

Fabrication of metallic and non-metallic top electrodes for large-area molecular junctions.

Molecular junctions have proven invaluable tools through which to explore the electronic properties of molecules and molecular monolayers. In seeking to develop a viable molecular electronics based technology it becomes essential to be able to reliably create larger area molecular junctions by contacting molecular monolayers to both bottom and top electrodes. The assembly of monolayers onto a conducting substrate by self-assembly, Langmuir-Blodgett and other methods is well established. However, the deposition of top-contact electrodes without film penetration or damage from the growing electrode material has proven problematic. This Review highlights the challenges of this area, and presents a selective overview of methods that have been used to solve these issues.

Soft palatal mass containing heterotopic neural tissue causing airway obstruction in a Pierre-Robin sequence patient.

Pierre-Robin sequence (PRS) patients frequently exhibit symptoms of airway obstruction due to multiple etiologies, predominantly from glossoptosis and tongue base obstruction. Rarely, these patients can have palatal mass and even rarer is one of neural origin. To date, there are few reports of heterotopic neural tissue causing airway obstruction in literature, and there are only two reports related to PRS. The objective of this report is to detail a PRS patient with obstructive airway symptoms that resolved after removal of a right-sided soft palatal mass containing heterotopic neural tissue. A 5-month-old boy with a past medical history of cleft palate, PRS status-post-mandibular distraction osteogenesis was hospitalized after continuing respiratory distress. Imaging showed a cystic submucosal mass that arose from the right soft palate. Trans-palatal and trans-oral approaches were applied for the removal. The patient tolerated the procedure well and his obstructive events have resolved at follow-up.

Assessing the quality of life in infants with deformational plagiocephaly.

This was a parent-reported outcome study on the impact of helmet therapy on the quality of life of infants with deformational plagiocephaly and their caregivers. Using survey-based analysis, we compared the quality of life in infants with deformational plagiocephaly with a cohort of their healthy peers. In addition, we compared infant quality of life before and after helmet therapy to evaluate the impact of this mainstay therapy for deformational plagiocephaly. Our results demonstrated that infants with plagiocephaly and their caregivers had a significantly decreased quality of life compared with healthy controls. This reframes our understanding of deformational plagiocephaly and emphasizes the need for therapeutic intervention in these individuals. A common therapeutic option - helmet remolding therapy - was shown to have no negative impact on quality of life, underscoring this as an appropriate therapeutic option. These data will allow us to counsel our future parents more effectively regarding the impact of deformational plagiocephaly and helmet therapy.

Shape controlled assembly of carboxylic acids: formation of a binary monolayer by intercalation into molecular nanotunnels.

Binary self-assembled monolayers (SAMs) combining a Y-shaped aromatic carboxylic acid (1,3,5-benzenetribenzoic acid, H3BTB) and a cage-type alicyclic carboxylic acid (adamantane carboxylic acid, AdCA) were investigated by scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and near edge X-ray absorption fine structure (NEXAFS) spectroscopy. The SAMs, prepared by molecular adsorption from solution on Au substrates modified by underpotential deposition of Ag, exhibit a pronounced dependence of their structure on the assembly protocol. Exposing an H3BTB SAM to AdCA, the highly regular row structure of the native H3BTB layer persists and STM imaging does not show signs of AdCA adsorption. This is in striking contrast to the disordered arrangements of H3BTB and the presence of AdCA employing the inverted adsorption sequence or coadsorption of the two molecules. However, spectroscopic analysis of the H3BTB SAM exposed to AdCA reveals the presence also of the latter, suggesting that the AdCA molecules are hidden in the nanotunnels of the H3BTB monolayer. Direct evidence for the intercalation of AdCA is obtained by STM manipulation experiments which lay bare areas of AdCA molecules upon local removal of H3BTB. Surprisingly, these are densely packed and arranged into a highly ordered monolayer. Formation of such a compact AdCA layer is explained by expulsion of AdCA from the H3BTB nanotunnels of the surrounding intact mixed SAM, driven by release of stress in the nanotunnels built up when AdCA is intercalated.

Nanotopography-based lymphatic delivery for improved anti-tumor responses to checkpoint blockade immunotherapy.

Rationale: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a co-inhibitory checkpoint receptor that is expressed by naïve T-cells in lymph nodes (LNs) to inhibit activation against "self" antigens (Ags). In cancer, anti-CTLA-4 blocks inhibitory action, enabling robust activation of T-cells against tumor Ags presented in tumor draining LNs (TDLNs). However, anti-CTLA-4 is administered intravenously with limited exposure within TDLNs and immune related adverse events (irAEs) are associated with over-stimulation of the immune system. Methods: Herein, we first deliver anti-CTLA-4 in an orthotopic mammary carcinoma murine model using a nanotopographical microneedle-array device to compare its anti-tumor response to that from systemic administration. Additionally, to demonstrate the feasibility of lymphatic delivery in humans using the device, we use near-infrared fluorescence imaging to image delivery of ICG to LNs. Results: Our data show that lymphatic infusion results in more effective tumor growth inhibition, arrest of metastases, increased tumor infiltrating lymphocytes and complete responses when compared to conventional systemic administration. In clinical studies, we demonstrate for the first time that nanotopographic infusion can deliver ICG through the lymphatics directly to the axilla and inguinal LNs of healthy human volunteers. Conclusion: Taken together, these results suggest that regional delivery using a nanotopography-based microneedle array could revolutionize checkpoint blockade immunotherapy by reducing systemic drug exposure and maximizing drug delivery to TDLNs where tumor Ags present. Future work is needed to determine whether lymphatic delivery of anti-CTLA-4 can alleviate irAEs that occur with systemic dosing.

PqsA Promotes Pyoverdine Production via Biofilm Formation.

Biofilms create an impermeable barrier against antimicrobial treatment and immune cell access, severely complicating treatment and clearance of nosocomial Pseudomonas aeruginosa infections. We recently reported that biofilm also contributes to pathogen virulence by regulating the production of the siderophore pyoverdine. In this study, we investigated the role of PqsA, a key cell-signaling protein, in this regulatory pathway. We demonstrate that PqsA promotes pyoverdine production in a biofilm-dependent manner. Under nutritionally deficient conditions, where biofilm and pyoverdine are decoupled, PqsA is dispensable for pyoverdine production. Interestingly, although PqsA-dependent pyoverdine production does not rely upon Pseudomonas quinolone signal (PQS) biosynthesis, exogenous PQS can also trigger biofilm-independent production of pyoverdine. Adding PQS rapidly induced planktonic cell aggregation. Moreover, these clumps of cells exhibit strong expression of pyoverdine biosynthetic genes and show substantial production of this siderophore. Finally, we surveyed the relationship between biofilm formation and pyoverdine production in various clinical and environmental isolates of P. aeruginosa to evaluate the clinical significance of targeting biofilm during infections. Our findings implicate PqsA in P. aeruginosa virulence by regulating biofilm formation and pyoverdine production.

Evaluating an undergraduate interprofessional simulation-based educational module: communication, teamwork, and confidence performing cardiac resuscitation skills.

PURPOSE: Interprofessional (IP) collaboration during cardiac resuscitation is essential and contributes to patient wellbeing. The purpose of this study is to evaluate an innovative simulation-based IP educational module for undergraduate nursing and medical students on cardiac resuscitation skills. METHODS: Nursing and medical trainees participated in a new cardiac resuscitation curriculum involving a 2-hour IP foundational cardiac resuscitation skills lab, followed by three 2-hour IP simulation sessions. Control group participants attended the existing two 2-hour IP simulation sessions. Study respondents (N = 71) completed a survey regarding their confidence performing cardiac resuscitation skills and their perceptions of IP collaboration. RESULTS: Despite a consistent positive trend, only one out of 17 quantitative survey items were significantly improved for learners in the new curriculum. They were more likely to report feeling confident managing the airway during cardiac resuscitation (P = 0.001). Overall, quantitative results suggest that senior nursing and medical students were comfortable with IP communication and teamwork and confident with cardiac resuscitation skills. There were no significant differences between nursing students' and medical students' results. Through qualitative feedback, participants reported feeling comfortable learning with students from other professions and found value in the IP simulation sessions. CONCLUSION: Results from this study will inform ongoing restructuring of the IP cardiac resuscitation skills simulation module as defined by the action research process. Specific improvements that are suggested by these findings include strengthening the team leader component of the resuscitation skills lab and identifying learners who may benefit from additional practice in the role of team leader and with other skills where they lack confidence.