A Multifunctional, Low Cost and Sustainable Neonatal Database System.

Continuous improvement in the clinical performance of neonatal intensive care units (NICU) depends on the use of locally relevant, reliable data. However, neonatal databases with these characteristics are typically unavailable in NICUs using paper-based records, while in those using electronic records, the inaccuracy of data and the inability to customize commercial data systems limit their usability for quality improvement or research purposes. We describe the characteristics and uses of a simple, neonatologist-centered data system that has been successfully maintained for 30 years, with minimal resources and serving multiple purposes, including quality improvement, administrative, research support and educational functions. Structurally, our system comprises customized paper and electronic components, while key functional aspects include the attending-based recording of diagnoses, integration into clinical workflows, multilevel data accuracy and validation checks, and periodic reporting on both data quality and NICU performance results. We provide examples of data validation methods and trends observed over three decades, and discuss essential elements for the successful implementation of this system. This database is reliable and easily maintained; it can be developed from simple paper-based forms or used to supplement the functionality and end-user customizability of existing electronic medical records. This system should be readily adaptable to NICUs in either high- or limited-resource environments.

Surfactant delivery by aerosol inhalation - past, present, and future.

Surfactant replacement therapy (SRT) by nebulization to spontaneously breathing patients has been regarded as the Holy Grail since surfactant deficiency was first identified as the cause for neonatal respiratory distress syndrome. It avoids neonatal endotracheal intubation, a procedure that is often difficult and occasionally harmful. Unapproved alternatives to endotracheal tube placement for liquid surfactant instillation, such as LISA (thin catheter intubation) and SALSA (supraglottic airway insertion) have significant merit but are still invasive, leaving nebulized SRT as the only truly non-invasive method. In the past 60 years, we have learned much about the potential - and limitations - of nebulized SRT. In this review, we examine the promises and pitfalls of nebulized SRT, discuss what we know about neonatal aerosol drug delivery and recap some of the most recent randomized clinical trials of nebulized SRT. We conclude with a discussion of what is known and the next steps needed if this type of SRT is to become a regular part of clinical care.

Towards estimating the carbon footprint of external beam radiotherapy.

PURPOSE: The National Health Service (NHS) in the United Kingdom (UK) is aiming to be carbon net zero by 2040 to help limit the dangerous effects of climate change. Radiotherapy contributes to this with potential sources quantified here. METHOD: Activity data for 42 patients from within the breast IMRT and prostate VMAT pathways were collected. Data for 20 prostate patients was also collected from 3 other centres to enable cross centre comparison. A process-based, bottom-up approach was used to calculate the carbon footprint. Additionally, patients were split into pre-COVID and COVID groups to assess the impact of protocol changes due to the pandemic. RESULTS: The calculated carbon footprint for prostate and breast pre-COVID were 148 kgCO2e and 101 kgCO2e respectively, and 226 kgCO2e and 75 kgCO2e respectively during COVID. The energy usage by the linac during treatment for a total course of radiotherapy for prostate treatments was 2-3 kWh and about 1 kWh for breast treatments. Patient travel made up the largest proportion (70-80%) of the calculated carbon footprint, with linac idle power second with âˆ¼ 10% and PPE and SF6 leakage were both between 2 and 4%. CONCLUSION: These initial findings highlight that the biggest contributor to the external beam radiotherapy carbon footprint was patient travel, which may motivate increased used of hypofractionation. Many assumptions and boundaries have been set on the data gathered, which limit the wider application of these results. However, they provide a useful foundation for future more comprehensive life cycle assessments.

Discovery of quinazoline HPK1 inhibitors with high cellular potency.

Hematopoietic progenitor kinase 1 (HPK1) is regarded as a highly validated target in pre-clinical immune oncology. HPK1 has been described as regulating multiple critical signaling pathway in both adaptive and innate cells. In support of this role, HPK1 KO T cells show enhanced sensitivity to TCR activation and HPK1 KO mice display enhanced anti-tumor activity. Taken together, inhibition of HPK1 has the potential to induce enhanced anti-tumor immune response. Herein, we described the discovery of highly potent HPK1 inhibitors starting form a weak HTS hit. Using a structure-based drug design, HPK1 inhibitors exhibiting excellent cellular single-digit nanomolar potency in both proximal (pSLP76) and distal (IL-2) biomarkers along with sustained elevation of IL-2 cytokine secretion were discovered.

Psychological predictors of consumer-level virtual reality technology adoption and usage.

In recent years, virtual reality (VR) technology has been mainstreamed for at-home use, with various consumer-oriented devices released by media firms such as Meta, Google, Samsung, and HTC. The present research investigates the role of psychological traits-including immersive tendencies, absorption, sensation seeking, need for cognition, neophobia, and belief in science-as well as trait levels of individual innovativeness, self-perception of social well-being, and owner demographics, in predicting VR adoption rates and sustained use over time. Separate analyses were conducted for different classes of VR device (fixed, mobile, and standalone devices). In general, psychological factors generally emerged as more determinative of adoption than did demographics. Users' immersive tendencies predicted earlier adoption of VR technology while absorption was associated with later adoption, with both predictive of higher overall initial usage of different types of devices. Additionally, perceiving oneself as socially successful was associated with higher initial VR usage, while a tendency to see one's emotions as influenced by in-person rather than online contacts was negatively associated with usage. Finally, belief in science predicted greater consistency in usage over time while higher levels of absorption were associated with unstable usage patterns. These findings expand upon the limited work previously investigating the role of individual differences in adoption of VR and mark the promise of psychometrics for understanding the diffusion and continued usage of consumer-facing VR devices.

Photoacoustic imaging is a novel tool to measure finger artery structure and oxygenation in patients with SSc.

Systemic sclerosis (SSc)-related digital ischaemia is a major cause of morbidity, resulting from a combination of microvascular and digital artery disease. Photoacoustic imaging offers a newly available, non-invasive method of imaging digital artery structure and oxygenation. The aim of this study was to establish whether photoacoustic imaging could detect and measure vasculopathy in digital arteries, including the level of oxygenation, in patients with SSc and healthy controls. 22 patients with SSc and 32 healthy controls (HC) underwent photoacoustic imaging of the fingers. Vascular volume and oxygenation were assessed across eight fingers at the middle phalanx. In addition, oxygenation change during finger occlusion was measured at the non-dominant ring finger and the vascular network was imaged along the length of one finger for qualitative assessment. There was no statistically significant difference in vascular volume between patients with SSc and HC (mean of eight fingers; SSc, median 118.6 IQR [95.0-130.5] vs. HC 115.6 [97.8-158.9]) mm3. However, baseline oxygenation (mean 8 fingers) was lower in SSc vs. HC (0.373 [0.361-0.381] vs. 0.381 [0.373-0.385] arbitrary sO2 units respectively; p = 0.03). Hyperaemic oxygenation response following occlusion release was significantly lower in SSc compared to HC (0.379 [0.376-0.381] vs. 0.382 [0.377-0.385]; p = 0.03). Whilst vascular volume was similar between groups, digital artery oxygenation was decreased in patients with SSc as compared to HC, indicative of functional deficit. Photoacoustic imaging offers an exciting new method to image the vascular network in patients with SSc and the possibility to capture oxygenation as a functional measure.

Care Levels for Fetal Therapy Centers.

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels for fetal therapy centers are proposed to match the anticipated care complexity, with appropriate resources to achieve an optimal outcome at an institutional and regional level. A level I fetal therapy center should be capable of offering fetal interventions that may be associated with obstetric risks of preterm birth or membrane rupture but that would be very unlikely to require maternal medical subspecialty or intensive care, with neonatal risks not exceeding those of moderate prematurity. A level II center should have the incremental capacity to provide maternal intensive care and to manage extreme neonatal prematurity. A level III therapy center should offer the full range of fetal interventions (including open fetal surgery) and be able manage any of the associated maternal complications and comorbidities, as well as have access to neonatal and pediatric surgical intervention including indicated surgery for neonates with congenital anomalies.

Postnatal Corticosteroids to Prevent or Treat Chronic Lung Disease Following Preterm Birth.

The American Academy of Pediatrics continues to provide guidance on the use of postnatal corticosteroids to manage or prevent chronic lung disease following preterm birth (formerly referred to as bronchopulmonary dysplasia). Since the last revision of such guidance in 2010, several prospective randomized trials have been published. This revision provides a review of those studies as well as updated recommendations, which include the use of systemic low-dose corticosteroid in preterm neonates with or at high risk for chronic lung disease. High-dose dexamethasone (≥0.5 mg/kg per day) is not recommended. New evidence suggests that inhaled corticosteroids may confer benefit if provided with surfactant as a vehicle, but safety data are lacking. Evidence remains insufficient to make any recommendations regarding routine use of postnatal corticosteroids in preterm infants. Neonatologists and other hospital care providers must continue to use their clinical judgment in individual patients, balancing the potential adverse effects of corticosteroid treatment with those of chronic lung disease. The decision to use postnatal corticosteroids for this purpose should be made together with the infant's parents, and the care providers should document their discussions with parents in the patient's medical record.

Return of individual research results from genomic research: A systematic review of stakeholder perspectives.

Despite the plethora of empirical studies conducted to date, debate continues about whether and to what extent results should be returned to participants of genomic research. We aimed to systematically review the empirical literature exploring stakeholders' perspectives on return of individual research results (IRR) from genomic research. We examined preferences for receiving or willingness to return IRR, and experiences with either receiving or returning them. The systematic searches were conducted across five major databases in August 2018 and repeated in April 2020, and included studies reporting findings from primary research regardless of method (quantitative, qualitative, mixed). Articles that related to the clinical setting were excluded. Our search identified 221 articles that met our search criteria. This included 118 quantitative, 69 qualitative and 34 mixed methods studies. These articles included a total number of 118,874 stakeholders with research participants (85,270/72%) and members of the general public (40,967/35%) being the largest groups represented. The articles spanned at least 22 different countries with most (144/65%) being from the USA. Most (76%) discussed clinical research projects, rather than biobanks. More than half (58%) gauged views that were hypothetical. We found overwhelming evidence of high interest in return of IRR from potential and actual genomic research participants. There is also a general willingness to provide such results by researchers and health professionals, although they tend to adopt a more cautious stance. While all results are desired to some degree, those that have the potential to change clinical management are generally prioritized by all stakeholders. Professional stakeholders appear more willing to return results that are reliable and clinically relevant than those that are less reliable and lack clinical relevance. The lack of evidence for significant enduring psychological harm and the clear benefits to some research participants suggest that researchers should be returning actionable IRRs to participants.

Screenomics: A Framework to Capture and Analyze Personal Life Experiences and the Ways that Technology Shapes Them.

Digital experiences capture an increasingly large part of life, making them a preferred, if not required, method to describe and theorize about human behavior. Digital media also shape behavior by enabling people to switch between different content easily, and create unique threads of experiences that pass quickly through numerous information categories. Current methods of recording digital experiences provide only partial reconstructions of digital lives that weave - often within seconds - among multiple applications, locations, functions and media. We describe an end-to-end system for capturing and analyzing the "screenome" of life in media, i.e., the record of individual experiences represented as a sequence of screens that people view and interact with over time. The system includes software that collects screenshots, extracts text and images, and allows searching of a screenshot database. We discuss how the system can be used to elaborate current theories about psychological processing of technology, and suggest new theoretical questions that are enabled by multiple time scale analyses. Capabilities of the system are highlighted with eight research examples that analyze screens from adults who have generated data within the system. We end with a discussion of future uses, limitations, theory and privacy.

Advancing peptide siRNA-carrier designs through L/D-amino acid stereochemical modifications to enhance gene silencing.

The 599 peptide has been previously shown to effectively deliver small interfering RNAs (siRNAs) to cancer cells, inducing targeted-oncogene silencing, with a consequent inhibition of tumor growth. Although effective, this study was undertaken to advance the 599 peptide siRNA-carrier design through L/D-amino acid stereochemical modifications. Consequently, 599 was modified to generate eight different peptide variants, incorporating either different stereochemical patterns of L/D-amino acids or a specific D-amino acid substitution. Upon analysis of the variants, it was observed that these modifications could, in some instances, increase/decrease the binding, nuclease/serum stability, and complex release of siRNAs, as well as influence the gene-silencing efficiencies of the complex. These modifications were also found to affect cellular uptake and intracellular localization patterns of siRNA cargo, with one particular variant capable of mediating binding of siRNAs to specific cellular projections, identified as filopodia. Interestingly, this variant also exhibited the most enhanced gene silencing in comparison to the parent 599 peptide, thus suggesting a possible connection between filopodia binding and enhanced gene silencing. Together, these data demonstrate the utility of peptide stereochemistry, as well as the importance of a key D-amino acid modification, in advancing the 599 carrier design for the enhancement of gene silencing in cancer cells.

Views on genomic research result delivery methods and informed consent: a review.

There has been little discussion of the way genomic research results should be returned and how to obtain informed consent for this. We systematically searched the empirical literature, identifying 63 articles exploring stakeholder perspectives on processes for obtaining informed consent about return of results and/or result delivery. Participants, patients and members of the public generally felt they should choose which results are returned to them and how, ranging from direct (face-to-face, telephone) to indirect (letters, emails, web-based delivery) communication. Professionals identified inadequacies in result delivery processes in the research context. Our findings have important implications for ensuring participants are supported in deciding which results they wish to receive or, if no choice is offered, preparing them for potential research outcomes.

Aerosolized Calfactant for Newborns With Respiratory Distress: A Randomized Trial.

BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers' discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.

Optimizing Resources in Children's Surgical Care: An Update on the American College of Surgeons' Verification Program.

Surgical procedures are performed in the United States in a wide variety of clinical settings and with variation in clinical outcomes. In May 2012, the Task Force for Children's Surgical Care, an ad hoc multidisciplinary group comprising physicians representing specialties relevant to pediatric perioperative care, was convened to generate recommendations to optimize the delivery of children's surgical care. This group generated a white paper detailing the consensus opinions of the involved experts. Following these initial recommendations, the American College of Surgeons (ACS), Children's Hospital Association, and Task Force for Children's Surgical Care, with input from all related perioperative specialties, developed and published specific and detailed resource and quality standards designed to improve children's surgical care (https://www.facs.org/quality-programs/childrens-surgery/childrens-surgery-verification). In 2015, with the endorsement of the American Academy of Pediatrics (https://pediatrics.aappublications.org/content/135/6/e1538), the ACS established a pilot verification program. In January 2017, after completion of the pilot program, the ACS Children's Surgery Verification Quality Improvement Program was officially launched. Verified sites are listed on the program Web site at https://www.facs.org/quality-programs/childrens-surgery/childrens-surgery-verification/centers, and more than 150 are interested in verification. This report provides an update on the ACS Children's Surgery Verification Quality Improvement Program as it continues to evolve.

Summit proceedings: Biomedical countermeasure development for emerging vector-borne viral diseases.

Emerging and re-emerging infectious diseases are an expanding global threat to public health, security, and economies. Increasing populations, urbanization, deforestation, climate change, anti-vaccination movements, war, and international travel are some of the contributing factors to this trend. The recent Ebola, MERS-CoV, and Zika outbreaks demonstrated we are insufficiently prepared to respond with proven safe and effective countermeasures (i.e., vaccines and therapeutics). The State University of New York Upstate Medical University and the Trudeau Institute convened a summit of key opinion and thought leaders in the life sciences and biomedical research and development enterprises to explore global biopreparedness challenges, take an inventory of existing capabilities and capacities related to preparation and response, assess current "gaps," and prospect what could be done to improve our position. Herein we describe the summit proceedings, "Translational Immunology Supporting Biomedical Countermeasure Development for Emerging Vector-borne Viral Diseases," held October 2-3, 2018, at the Trudeau Institute in Saranac Lake, NY.