Modelling and Characterisation of Orthotropic Damage in Aluminium Alloy 2024.

The aim of the work presented in this paper was development of a thermodynamically consistent constitutive model for orthotopic metals and determination of its parameters based on standard characterisation methods used in the aerospace industry. The model was derived with additive decomposition of the strain tensor and consisted of an elastic part, derived from Helmholtz free energy, Hill's thermodynamic potential, which controls evolution of plastic deformation, and damage orthotopic potential, which controls evolution of damage in material. Damage effects were incorporated using the continuum damage mechanics approach, with the effective stress and energy equivalence principle. Material characterisation and derivation of model parameters was conducted with standard specimens with a uniform cross-section, although a number of tests with non-uniform cross-sections were also conducted here. The tests were designed to assess the extent of damage in material over a range of plastic deformation values, where displacement was measured locally using digital image correlation. The new model was implemented as a user material subroutine in Abaqus and verified and validated against the experimental results for aerospace-grade aluminium alloy 2024-T3. Verification was conducted in a series of single element tests, designed to separately validate elasticity, plasticity and damage-related parts of the model. Validation at this stage of the development was based on comparison of the numerical results with experimental data obtained in the quasistatic characterisation tests, which illustrated the ability of the modelling approach to predict experimentally observed behaviour. A validated user material subroutine allows for efficient simulation-led design improvements of aluminium components, such as stiffened panels and the other thin-wall structures used in the aerospace industry.

Paediatric excipient risk assessment (PERA) tool and application for selecting appropriate excipients for paediatric dosage forms - Part 2.

It is necessary to use a scientifically sound process for excipient risk evaluation, selection, and management in order to develop paediatric medicinal products that are both safe and effective. The "Paediatric Excipient Risk Assessment (PERA)" framework, which proposes a comprehensive approach by considering all relevant factors related to patient, dosage form, and excipient attributes, was developed and published as part 1 of this paper series, to enable the rational selection of excipients for paediatric medicinal products. This article is Part 2 of the series and presents the PERA tool that allows easy adoption of the PERA framework. Using a straightforward heat map scoring approach (Red, Yellow, and Green category) for risk evaluation, the PERA tool can be used to compare and choose excipients. The PERA tool will help users identify potential gaps in excipients information that will help with risk-based mitigation planning. Several case studies covering frequently used and novel excipients for oral, as well as the choice of excipient for parenteral products for neonatal administration, serve to illustrate the PERA tool's usefulness.

Selecting appropriate excipients for paediatric dosage form - Paediatric excipients risk assessment (PERA) framework - Part 1.

Excipients are often the major component of the formulation that critically affect the dosage form, manufacturing process, product performance, stability and safety. They exert different roles and functions in a dosage form. Selecting excipients with appropriate safety and tolerability is a major hurdle in paediatric formulation development. The suitability of a particular excipient will be dependent on the context of its use with regard to the paediatric age range, acute versus chronic use, and clinical risk-benefit of the disease, active and excipient. Scientists are encouraged to apply the principle of risk-benefit to assess the suitability of excipients to the specific paediatric population. Indicative list of parameters that should be taken into consideration and hierarchy of information sources when assessing the excipients risks is provided by regulatory agencies. However, the approach to be taken and details of how the risk evaluation should be undertaken are lacking. There is a need for a systematic approach to selection of excipients and assessment of the risk of excipient exposure. The Paediatric Excipients Risk Assessment (PERA) framework developed and proposed in this paper provides a structured, systematic decision-making framework via customizable tools and processes that can help to improve the transparency and communications on the selection and justification of use of excipients in a paediatric formulation.

Safety climate and seat belt use in the fire service.

OBJECTIVE: Motor vehicle incidents or apparatus crashes are a leading cause of firefighter fatalities in the United States. Nonuse of seat belts has been linked to some of these fatalities. This research seeks to understand the relationship between safety climate and seat belt use among firefighters, as findings will provide insights into factors that may bolster seat belt use and protect firefighters. METHODS: Data were collected from 208 career firefighters working for a city fire department in the southeastern United States. Structural equation modeling was used to test a hypothesized model and to assess the relationships between organizational safety climate, work group safety climate and seat belt use. RESULTS: It was determined that positive perceptions of workgroup safety climate, as a higher order factor, comprised of supervisor support, horizontal cohesion, and vertical cohesion, was positively associated with seat belt use within a sample of firefighters. Organizational level safety climate did not have a significant relationship with seat belt use but did positively influence workgroup safety climate perceptions. CONCLUSIONS: Safety climate has been associated with safety compliance and participation behaviors, but more research was needed to specifically examine the impact of safety climate on seat belt use in firefighters. The findings point to the importance of safety climate as a leading indicator and predictor of seat belt use. Bolstering safety climate through safety programs, commitment to safety, effective communication, supportive supervisors and cohesion should ultimately aid in bolstering seat belt use among firefighters, which is important to curtailing firefighter injuries and fatalities.

Feasibility of risk assessment for breast cancer molecular subtypes.

PURPOSE: Few breast cancer risk assessment models account for the risk profiles of different tumor subtypes. This study evaluated whether a subtype-specific approach improves discrimination. METHODS: Among 3389 women who had a screening mammogram and were later diagnosed with invasive breast cancer we performed multinomial logistic regression with tumor subtype as the outcome and known breast cancer risk factors as predictors. Tumor subtypes were defined by expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) based on immunohistochemistry. Discrimination was assessed with the area under the receiver operating curve (AUC). Absolute risk of each subtype was estimated by proportioning Gail absolute risk estimates by the predicted probabilities for each subtype. We then compared risk factor distributions for women in the highest deciles of risk for each subtype. RESULTS: There were 3,073 ER/PR+ HER2 - , 340 ER/PR +HER2 + , 126 ER/PR-ER2+, and 300 triple-negative breast cancers (TNBC). Discrimination differed by subtype; ER/PR-HER2+ (AUC: 0.64, 95% CI 0.59, 0.69) and TNBC (AUC: 0.64, 95% CI 0.61, 0.68) had better discrimination than ER/PR+HER2+ (AUC: 0.61, 95% CI 0.58, 0.64). Compared to other subtypes, patients at high absolute risk of TNBC were younger, mostly Black, had no family history of breast cancer, and higher BMI. Those at high absolute risk of HER2+ cancers were younger and had lower BMI. CONCLUSION: Our study provides proof of concept that stratifying risk prediction for breast cancer subtypes may enable identification of patients with unique profiles conferring increased risk for tumor subtypes.

Unveiling Trends: Nanoscale Materials Shaping Emerging Biomedical Applications.

The realm of biomedical materials continues to evolve rapidly, driven by innovative research across interdisciplinary domains. Leveraging big data from the CAS Content Collection, this study employs quantitative analysis through natural language processing (NLP) to identify six emerging areas within nanoscale materials for biomedical applications. These areas encompass self-healing, bioelectronic, programmable, lipid-based, protein-based, and antibacterial materials. Our Nano Focus delves into the multifaceted utilization of nanoscale materials in these domains, spanning from augmenting physical and electronic properties for interfacing with human tissue to facilitating intricate functionalities like programmable drug delivery.

Racial Disparities in Breast Cancer Genetic Testing May be Mitigated by Counseling.

BACKGROUND: Currently, racial disparities exist in access to genetic testing. Recent developments have helped narrow the gap in accessibility. The purpose of this study was to determine whether racial disparities in genetic consultation attendance and completion of genetic testing persist, and, if so, factors that contribute to under-utilization of these resources. METHODS: A single-institution retrospective review of breast patients referred for genetic counseling between 2017 and 2019 was performed. Univariate and multivariate logistic regression evaluated factors associated with genetic counseling attendance and genetic testing. RESULTS: A total of 596 patients were referred for genetic counseling: 433 (72.7%) white; 138 (23.2%) black; and 25 (4.2%) other or unknown. In multivariate analysis, black patients, patients without breast cancer family history, and patients without a current cancer diagnosis, classified as high risk, were significantly less likely to attend their genetics appointment (p = 0.010, p = 0.007, p = 0.005, respectively). Age, insurance type, distance from facility, and need for chemotherapy did not significantly impact consult completion rate. Of the patients who completed a genetic consult, 84.4% (n = 248) had genetic testing and 17.7% (n = 44) had a pathogenic variant. For patients who attended counseling, there were no significant factors that were predictive with receipt of genetic testing. CONCLUSIONS: In this study, there was a significant association between race and attending genetic counseling. Once counseled, most patients went on to receive genetic testing, and racial disparities in testing disappeared, emphasizing the value of providing additional education about the importance and purpose of genetic testing.

Impact of P-gp inhibition on systemic exposure of pralsetinib and dosing considerations.

A study to determine the impact of cyclosporine (Neoral), an inhibitor of P-gp, on the pharmacokinetics of pralsetinib (trade name GAVRETO®) was conducted in 15 healthy adult volunteers. A single 200 mg dose of pralsetinib was administered orally alone and in combination with cyclosporine with a 9-day washout between treatments. Co-administration with cyclosporine resulted in a clinically relevant increase in pralsetinib maximum plasma concentration (Cmax) and area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) with associated geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of 148% (109, 201) and 181% (136, 241), respectively. These findings provide insight into concomitant dosing of pralsetinib with inhibitors of P-gp given the increases in pralsetinib exposure observed when administered with cyclosporine. Based on these results, co-administration of pralsetinib with P-gp inhibitors is not recommended. In the event that co-administration cannot be avoided, it is recommended that the dose of pralsetinib be reduced.

Access to an Educational Video Preoperatively Has No Effect on Postoperative Opioid Use After Arthroscopic Partial Meniscectomy of the Knee: A Prospective Cohort Study.

Purpose: To determine whether access to a website with an educational video would decrease postoperative opioid use in patients undergoing arthroscopic partial meniscectomy. Methods: Enrolled patients who underwent arthroscopic partial meniscectomy at a single center were randomized to either the intervention or control group prior to surgery. The intervention group received a card with access to an online educational video regarding opioids with their postoperative instructions; the control group did not. The online video was just over 5 minutes long and contained general information about the dangers of opioid use, how to safely dispose of unused opioids, and local support contact information. Data were collected by telephone 10 to 14 days postoperatively and analyzed with GraphPad Prism version 9.5.0. Patient characteristics including age, sex, body mass index, allergies, smoking, depression, alcohol abuse, American Society of Anesthesiologists level, diagnosis of chronic obstructive pulmonary disease, hypertension, diabetes, substance abuse, employment status, workers' compensation, and sports participation were analyzed and correlated with postoperative opioid use. Results: A total of 166 patients were included in this study, with 78 in the control group and 88 in the intervention group. Mean number of pills consumed was 3 in the control group and 2.2 in the intervention group. This difference did not reach statistical significance. Patients who were obese, smokers, or diagnosed with depression both consumed more opioids and were less likely to take no narcotics postoperatively. Patients who participated in sports consumed fewer total opioids on average than those who did not. Subgroup analysis of patients with higher risk factors did not show a difference between the control and intervention groups in the average amount of opioid used or the likelihood of using no narcotics. Among all patients, 82 (49%) used no narcotics postoperatively and 90% used 8 or fewer tablets. Conclusions: Directing patients to an educational website and video is not an effective tool in decreasing opioid consumption. Patients undergoing arthroscopic meniscectomy who are obese, active smokers, and clinically depressed or do not participate in sports are likely to use more postoperative narcotics. Regardless of access to the online educational video, half of patients used no narcotics. Level of Evidence: Level II, prospective cohort.

How the COVID-19 pandemic signaled the demise of Antarctic exceptionalism.

This paper explores how the COVID-19 pandemic affected science and tourism activities and their governance in the Antarctic and Southern Ocean. The pandemic reduced the ability of Antarctic Treaty Parties to make decisions on policy issues and placed a considerable burden on researchers. Tourism was effectively suspended during the 2020-2021 Antarctic season and heavily reduced in 2021-2022 but rebounded to record levels in 2022-2023. The pandemic stimulated reflection on practices to facilitate dialog, especially through online events. Opportunities arose to integrate innovations developed during the pandemic more permanently into Antarctic practices, in relation to open science, reducing operational greenhouse gas footprints and barriers of access to Antarctic research and facilitating data sharing. However, as well as the long-term impacts arising directly from the pandemic, an assemblage of major geopolitical drivers are also in play and, combined, these signal a considerable weakening of Antarctic exceptionalism in the early Anthropocene.

TerrANTALife 1.0 Biodiversity data checklist of known Antarctic terrestrial and freshwater life forms.

Background: Incomplete species inventories for Antarctica represent a key challenge for comprehensive ecological research and conservation in the region. Additionally, data required to understand population dynamics, rates of evolution, spatial ranges, functional traits, physiological tolerances and species interactions, all of which are fundamental to disentangle the different functional elements of Antarctic biodiversity, are mostly missing. However, much of the fauna, flora and microbiota in the emerged ice-free land of the continent have an uncertain presence and/or unresolved status, with entire biodiversity compendia of prokaryotic groups (e.g. bacteria) being missing. All the available biodiversity information requires consolidation, cross-validation, re-assessment and steady systematic inclusion in order to create a robust catalogue of biodiversity for the continent. New information: We compiled, completed and revised eukaryotic species inventories present in terrestrial and freshwater ecosystems in Antarctica in a new living database: terrANTALife (version 1.0). The database includes the first integration in a compendium for many groups of eukaryotic microorganisms. We also introduce a first catalogue of amplicon sequence variants (ASVs) of prokaryotic biodiversity. Available compendia and literature to date were searched for Antarctic terrestrial and freshwater species, integrated, taxonomically harmonised and curated by experts to create comprehensive checklists of Antarctic organisms. The final inventories comprises 470 animal species (including vertebrates, free-living invertebrates and parasites), 306 plants (including all Viridiplantae: embryophytes and green algae), 997 fungal species and 434 protists (sensu lato). We also provide a first account for many groups of microorganisms, including non-lichenised fungi and multiple groups of eukaryotic unicellular species (Stramenophila, Alveolata and Rhizaria (SAR), Chromists and Amoeba), jointly referred to as "protists". In addition, we identify 1753 bacterial (obtained from 348117 ASVs) and 34 archaeal genera (from 1848 ASVs), as well as, at least, 14 virus families. We formulate a basic tree of life in Antarctica with the main lineages listed in the region and their "known-accepted-species" numbers.

Systematic conservation planning for Antarctic research stations.

The small ice-free areas of Antarctica are essential locations for both biodiversity and scientific research but are subject to considerable and expanding human impacts, resulting primarily from station-based research and support activities, and local tourism. Awareness by operators of the need to conserve natural values in and around station and visitor site footprints exists, but the cumulative nature of impacts often results in reactive rather than proactive management. With human activity spread across many isolated pockets of ice-free ground, the pathway to the greatest reduction of human impacts within this natural reserve is through better management of these areas, which are impacted the most. Using a case study of Australia's Casey Station, we found significant natural values persist within the immediate proximity (<10 m) of long-term station infrastructure, but encroachment by physical disturbance results in ongoing pressures. Active planning to better conserve such values would provide a direct opportunity to enhance protection of Antarctica's environment. Here we introduce an approach to systematic conservation planning, tailored to Antarctic research stations, to help managers improve the conservation of values surrounding their activity locations. Use of this approach provides a potential mechanism to balance the need for scientific access to the continent with international obligations to protect its environment. It may also facilitate the development of subordinate conservation tools, including management plans and natural capital accounting. By proactively minimising and containing their station footprints, national programs can also independently demonstrate their commitment to protecting Antarctica's environment.

Implementation Mapping for Managing Patients at High Risk for Hereditary Cancer.

INTRODUCTION: Currently, no standard workflow exists for managing patients with pathogenic variants that put them at higher risk for hereditary cancers. Therefore, follow-up care for individuals with pathogenic variants is logistically challenging and results in poor guideline adherence. To address this challenge, authors created clinical management strategies for individuals identified at high risk for hereditary cancers. METHODS: An implementation mapping approach was used to develop and evaluate the establishment of a Hereditary Cancer Clinic at the Medical University of South Carolina throughout in 2022. This approach consisted of 5 steps: conduct a needs assessment, identify objectives, select implementation strategies, produce implementation protocols, and develop an evaluation plan. The needs assessment consisted of qualitative interviews with patients (n=11), specialists (n=9), and members of the implementation team (n=4). Interviews were coded using the Consolidated Framework for Implementation Research to identify barriers and facilitators to establishment of the Hereditary Cancer Clinic. Objectives were identified, and then the team selected implementation strategies and produced implementation protocols to address concerns identified during the needs assessment. Authors conducted a second round of patient interviews to assess patient education materials. RESULTS: The research team developed a long-term evaluation plan to guide future assessment of implementation, service, and clinical/patient outcomes. CONCLUSIONS: This approach provides the opportunity for real-time enhancements and impact, with strategies for care specialists, patients, and implementation teams. Findings support ongoing efforts to improve patient management and outcomes while providing an opportunity for long-term evaluation of implementation strategies and guidelines for patients at high risk for hereditary cancers.

Loss of research and operational equipment in Antarctica: Balancing scientific advances with environmental impact.

Antarctica has been subject to widespread, long-term and on-going human activity since the establishment of permanent research stations became common in the 1950s. Equipment may become intentionally or inadvertently lost in Antarctic marine and terrestrial environments as a result of scientific research and associated support activities, but this has been poorly quantified to date. Here we report the quantity and nature of equipment lost by the UK's national operator in Antarctica, the British Antarctic Survey (BAS). Over the 15-year study period (2005-2019), 125 incidents of loss were reported, with c. 23 tonnes of equipment lost of which 18% by mass was considered hazardous. The geographical distribution of lost equipment was widespread across the BAS operational footprint. However, impacts are considered low compared to those associated with research station infrastructure establishment and operation. To reduce environmental impact overall, we recommend that, where possible, better use is made of existing research station capacity to facilitate field research, thereby reducing the need for construction of new infrastructure and the generation of associated impacts. Furthermore, to facilitate reporting on the state of the Antarctic environment, we recommend that national Antarctic programmes reinvigorate efforts to comply with Antarctic Treaty System requirements to actively record the locations of past activities and make available details of lost equipment. In a wider context, analogous reporting is also encouraged in other pristine areas subject to new research activities, including in other remote Earth environments and on extra-terrestrial bodies.

Successful Development of a Natural Language Processing Algorithm for Pancreatic Neoplasms and Associated Histologic Features.

OBJECTIVES: Natural language processing (NLP) algorithms can interpret unstructured text for commonly used terms and phrases. Pancreatic pathologies are diverse and include benign and malignant entities with associated histologic features. Creating a pancreas NLP algorithm can aid in electronic health record coding as well as large database creation and curation. METHODS: Text-based pancreatic anatomic and cytopathologic reports for pancreatic cancer, pancreatic ductal adenocarcinoma, neuroendocrine tumor, intraductal papillary neoplasm, tumor dysplasia, and suspicious findings were collected. This dataset was split 80/20 for model training and development. A separate set was held out for testing purposes. We trained using convolutional neural network to predict each heading. RESULTS: Over 14,000 reports were obtained from the Mass General Brigham Healthcare System electronic record. Of these, 1252 reports were used for algorithm development. Final accuracy and F1 scores relative to the test set ranged from 95% and 98% for each queried pathology. To understand the dependence of our results to training set size, we also generated learning curves. Scoring metrics improved as more reports were submitted for training; however, some queries had high index performance. CONCLUSIONS: Natural language processing algorithms can be used for pancreatic pathologies. Increased training volume, nonoverlapping terminology, and conserved text structure improve NLP algorithm performance.

Mainstreamed genetic testing of breast cancer patients: experience from a single surgeon's practice in a large US Academic Center.

This study evaluated the impact of mainstreamed genetic testing (MGT) on the timing and uptake of testing in an academic breast surgeon's practice. Before September 2019 (pre-MGT phase), a breast surgery practice at Massachusetts General Hospital followed a traditional model of a pre-test consultation with a genetic counselor (GC) following a referral. After September 2019 (post-MGT phase), the same practice offered patients genetic testing in a single clinical encounter with a breast surgeon. We evaluated the waiting time between referral and GC visit in the pre-MGT phase and compared the uptake and positivity rates between both phases. In the pre-MGT phase (204 patients), the median waiting time for GC visit was seven days for patients with a newly diagnosed cancer, 211 days for patients with a personal history of cancer, and 224 days for non-cancer patients who had a family history. A total of 105 (51.5%) patients completed a GC appointment. In the post-MGT phase (202 patients), a significantly higher proportion of patients (88.1%, p < 0.001) consented to genetic testing, while the proportion of patients who tested positive was lower (pathogenic variant: 11.9% vs. 20.0%; variant of uncertain significance: 19.9% vs. 28.0%; p = 0.047). Implementing MGT can reduce the number of clinical visits, significantly shorten patients' wait time to test initiation, and increase the completion of genetic testing. Successful integration of this model relied on the genetic expertise of the breast surgeon involved and the support of the GC team.