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The theory of periodic Barlow multi-lattices ( X 1 X 2 ... X N ) ∞ with Xi ∈ {A, B, C} and Xi ≠ Xi+1 of stacked two-dimensional hexagonal close-packed layers is presented and used to derive exact lattice sum expressions in terms of fast converging Bessel function expansions for inverse power potentials. We describe in detail the mathematical properties of Barlow sphere packings and demonstrate that only two basic lattice sums are required to describe all periodic packings. For the sticky hard-sphere model with an attractive inverse power law potential, we find a linear correlation between the cohesive energies of different Barlow packings and the face-centered cubic packing fraction. We introduce an efficient algorithm for enumerating the unique periodic Barlow sequences for any given period N. The theory and lattice sums introduced here pave the way for the future treatment of Barlow multi-lattices. [ABSTRACT FROM AUTHOR]

We characterize the self-assembly and phase behavior of Janus rods over a broad range of temperatures and volume fractions, using Langevin dynamics simulations and free energy calculations. The Janus rods consist of a line of fused overlapping spheres that interact via a soft-core repulsive potential, with the addition of an attractive pseudo-square-well tail to a fraction of the spheres (the coverage) ranging from 5% to 100% of sites. Competition between the stability of liquid crystal phases originating from shape anisotropy and assembly driven by directional interactions gives rise to a rich polymorphism that depends on the coverage. At low densities near the Boyle temperature, we observe the formation of spherical and tubular micelles at low coverages, while at higher coverages, randomly oriented monolayers form as the attractive parts of the rods overlap. At higher densities, bilayer structures appear and merge to form smectic and crystalline lamellar phases. All these structures gradually become unstable as the temperature is increased until eventually regular nematic and smectic phases appear, consistent with the hard rod limit. Our results indicate that the intermediate regime where shape-entropic effects compete with anisotropic attractions provided by site specificity is rich in structural possibilities and should help guide the design of rod-like colloids for specific applications. [ABSTRACT FROM AUTHOR]

Prior work has demonstrated the presence of hysteresis effects in the control of affordance-guided behavior, in that behavioral transitions around a critical action boundary vary with directions of change in said action boundary. To date, research on this topic has overlooked the influence of the global context on these phenomena. We employ an affordance-based reaching task, whereby participants were asked to move a target to a goal by passing through one of two apertures (size variable or size constant). It was found that the direction of change in the size of the variable aperture influenced the point of behavioral transitions, and this effect interacted with the location of a given goal. In addition, we considered fluctuations in the entropy of participants' reach trajectories as a window into the nature of the behavioral phase transitions. Differences in the structure of entropy were found depending on the direction of change in the size variable aperture. These results are discussed in light of a dynamical systems approach, and recommendations for future work are made. [ABSTRACT FROM AUTHOR]

Purpose: To explore the effect of adding an allogeneic soft tissue graft at the time of single implant placement using a fully digital workflow for implant placement and restoration without making either analog or digital impressions. Materials and Methods: A prospective randomized clinical study was performed enrolling 39 participants requiring single-tooth implants. The patients were randomized into one of two groups: (1) the graft group, which received an allogeneic dermal graft at the time of implant placement (n = 19), or (2) the nongraft group (n = 20). A fully digital surgical and restorative protocol was implemented for both groups. Intraoral scans were taken before implant placement (T0), at the time of final crown delivery (T1), and 1 year after placement (T2). Intraoral scans were aligned using Geomagic Control X 2020 software, and linear and volumetric changes in buccal tissues were measured at T0, T1, and T2. Implant survival, probing depths (PDs), and complications were recorded. Participants were asked to complete an Oral Health Impact Profile (OHIP)-14 survey at T0 and T2. Marginal bone levels were measured at T0 and T2 on periapical radiographs. Results: Overall, 39 participants completed surgery and restoration in the incisor, canine, premolar, and molar sites. Two early failures were recorded in central incisor positions (95% survival). Crown delivery without complication from the digital workflow (impressionless) was achieved for 36 out of 39 cases (92%), and implant depth control was the main challenge. At 1 year, 37 participants attended the follow-up appointment. Both groups showed gain in buccal tissue thickness without significant differences between the two groups for both linear and volumetric measurements (P > .05). Soft tissue grafting was associated with minimal added morbidity. The interproximal marginal bone changes were recorded as follows: -0.16 mm mesial and -0.12 mm distal for the graft group and -0.01 mm mesial and -0.11 mm distal for the nongraft group (P = .07 for mesial and .83 for distal). The OHIP score was significantly reduced at T2 compared to T0 (P = .003) for the entire cohort. Conclusions: Augmentation of the alveolar mucosa on the buccal aspect of single-tooth implants is associated with clinically favorable outcomes. A fully digital workflow has been validated to permit crown delivery on CAD/CAM abutments without implant impressions. [ABSTRACT FROM AUTHOR]

Indium selenide is a polymorphous material system that has attracted considerable attention due to the outstanding electronic, optical, ferroelectric, and antiferroelectric properties of its various crystalline phases; however, this polymorphism adds a layer of complexity to the analysis of Raman and x-ray photoelectron (XPS) data of these materials. In this report, a method of quantitative analysis of combined Raman and XPS data is developed to determine the stoichiometry of indium selenide thin films, as well as the phase fraction of β-In2Se3, γ-In2Se3, and κ-In2Se3 within the films. A 13:1 ratio of the indium to selenium sensitivity factors (σIn/σSe = 13) was found to yield the most accurate stoichiometry results. Further structural characterization of the κ-In2Se3 film was performed and points to its existence in these films as a distinct phase, rather than strained γ-In2Se3. [ABSTRACT FROM AUTHOR]

Background: Goal setting is commonly used for promoting physical activity (PA) among insufficiently active individuals. Previous reviews have analyzed the effects of goal setting on PA, but the purpose of this systematic review was to examine the concurrent effects of goal setting on PA and psychological outcomes in insufficiently active individuals to support interventions aiming to produce sustained PA behavior change. Methods: In this review (PROSPERO: CRD42021243970), we identified 13 studies with 1208 insufficiently active adults that reported the effects of goal-setting interventions (range 3–24 wk) on both PA and psychological outcomes (eg, self-efficacy, motivation, and affect). We used meta-analysis and narrative synthesis to analyze these effects. Results: All goals used in the included studies were specific goals. Setting specific goals had a large, positive effect on PA (g [standard mean difference] = 1.11 [P <.001]; 95% confidence interval, 0.74–1.47), but only a small, positive effect on the combined psychological outcomes (g [standard mean difference] = 0.25 [P <.001]; 95% CI, 0.10–0.40). Moderator analyses revealed that interventions that did not reward participants had a significantly greater effect on PA than interventions that did provide rewards (g = 1.30 vs 0.60, respectively, P ≤.003). No other significant moderators were found. Conclusion: Our review offers initial insight into the long-term effects of specific goals on PA and psychological outcomes in insufficiently active adults. Further research that examines the PA and psychological effects of goal-setting interventions and investigates a wider range of goal types could develop a stronger evidence base to inform intervention for insufficiently active individuals. [ABSTRACT FROM AUTHOR]

The Australian Credentialled Diabetes Educator (CDE) registered trademark signifies quality care and education to those with diabetes. A review of the Australian Diabetes Educators Association (ADEA) CDE pathway was undertaken to ensure the quality of the CDE credential. The purpose of this study was to examine perceptions of the diabetes education workforce on the current pathway for educating and qualifying CDEs for practice. Stakeholders (e.g. CDEs, students, supervisors, course coordinators) were invited via the ADEA email, e-newsletter and Facebook to complete a 34-item online survey exploring their perceptions of the pathway, focusing on the requisite graduate certificate and subsequent credentialling requirements. Most (80%) of the 319 respondents were CDEs, 15% were CDEs in training and 12% were supervisors or employers. Half of participants (46%) indicated that graduate certificate course alumni were somewhat or very unprepared to take on the role of a diabetes educator (DE) prior to undertaking credentialling to become a CDE. Seventy-one percent of participants indicated more, and a greater variety, of clinical experiences are necessary within the course. Participants recommended formal assessment of competence within the clinical setting. Fifty-four percent of participants disagreed or were unsure that the subsequent credentialling pathway equips CDEs well for practice, indicating it is too onerous, and supported a more streamlined pathway. Findings highlight the need for education and skills-based training beyond the graduate certificate, and assessment of competence in conducting core diabetes skills to better equip CDEs for their role. [ABSTRACT FROM AUTHOR]

Aim: To assess student nurses understanding and skills in the application of antimicrobial stewardship knowledge to practice. Design: Quantitative. Methods: Cross‐sectional survey. Results: Five hundred and twenty three student nurses responded across 23 UK universities. Although students felt prepared in competencies in infection prevention and control, patient‐centred care and interprofessional collaborative practice, they felt less prepared in competencies in which microbiological knowledge, prescribing and its effect on antimicrobial stewardship is required. Problem‐based learning, activities in the clinical setting and face‐to‐face teaching were identified as the preferred modes of education delivery. Those who had shared antimicrobial stewardship teaching with students from other professions reported the benefits to include a broader understanding of antimicrobial stewardship, an understanding of the roles of others in antimicrobial stewardship and improved interprofessional working. Conclusion: There are gaps in student nurses' knowledge of the basic sciences associated with the antimicrobial stewardship activities in which nurses are involved, and a need to strengthen knowledge in pre‐registration nurse education programmes pertaining to antimicrobial management, specifically microbiology and antimicrobial regimes and effects on antimicrobial stewardship. Infection prevention and control, patient‐centred care and interprofessional collaborative practice are areas of antimicrobial stewardship in which student nurses feel prepared. Interprofessional education would help nurses and other members of the antimicrobial stewardship team clarify the role nurses can play in antimicrobial stewardship and therefore maximize their contribution to antimicrobial stewardship and antimicrobial management. Implications for the Profession: There is a need to strengthen knowledge from the basic sciences, specifically pertaining to antimicrobial management, in pre‐registration nurse education programmes. Patient or Public Contribution: No patient or public contribution. Impact: What Problem Did the Study Address?: Nurses must protect health through understanding and applying antimicrobial stewardship knowledge and skills (Nursing and Midwifery Council 2018); however, there is no research available that has investigated nurses understanding and skills of the basic sciences associated with the antimicrobial stewardship activities in which they are involved. What Were the Main Findings?: There are gaps in student nurses' knowledge of the basic sciences (specifically microbiology and prescribing) associated with the antimicrobial stewardship activities in which nurses are involved. Problem‐based learning, and activities in the clinical setting, were reported as useful teaching methods, whereas online learning, was seen as less useful. Where and on Whom Will the Research Have an Impact?: Pre‐registration nurse education programmes. Reporting Method: The relevant reporting method has been adhered to, that is, STROBE. [ABSTRACT FROM AUTHOR]

Despite the increasing use of assistive mobility devices, practical education to navigate real-world ground transportation barriers is lacking. The educational board game, called HERL-Town, was developed to teach safe and effective navigation for mobility device users (MDUs) in the community. The study examined the initial validity, reliability, and overall quality of HERL-Town as an educational tool for overcoming transportation barriers in real-world environments. HERL-Town featured fifty scenarios focused on transportation barriers and strategies, which were assessed for content validity, while the game quality was evaluated using the Model for the Evaluation of Educational Games (MEEGA+) tool. Twenty-three experienced MDUs and four caregivers participated in the study. The results indicated a good quality score of 60.15 and forty-five scenarios met the content validity standards. The overall reliability of the scenarios was moderate (ICC = 0.729). Early psychometric findings suggest HERL-Town as a promising effective educational game for helping new MDUs and their travel companions navigate safe and effective ground transportation barriers, hence enhancing their confidence, independence, and participation in the community. [ABSTRACT FROM AUTHOR]

Background: Caregivers experience high rates of occupational injuries, especially during wheelchair transfers, which often result in back pain and musculoskeletal disorders due to the physical demands of lifting and repositioning. While mechanical floor lifts, the current standard, reduce back strain, they are time-consuming and require handling techniques that subject caregivers to prolonged and repeated non-neutral trunk postures, increasing the risk of long-term back injuries. Aims: The aim was to assess the time efficiency and ergonomics of the powered personal transfer system (PPTS), a robotic transfer device designed for bed-to/from-wheelchair transfers. Methods: We evaluated transfers with the PPTS and mechanical lift with eight able-bodied participants who assisted with transfers between a bed and a wheelchair. Inertial measurement units (IMUs) were placed on participants to track their motion and assess trunk joint angles during transfers. Results: The PPTS significantly reduced the transfer time (144.31 s vs. 525.82 s, p < 0.001) and required significantly less range of motion for trunk flexion (p < 0.001), lateral bending (p = 0.008), and axial rotation (p = 0.001), all of which have been associated with back injuries. Additionally, the PPTS significantly reduced the time caregivers spent in non-neutral trunk postures, potentially lowering injury risks. Conclusions: These findings suggest that the PPTS improves transfer efficiency and caregiver safety, offering a promising alternative to the current standard of care for wheelchair-to/from-bed transfers. [ABSTRACT FROM AUTHOR]

Block copolymer self-assembly in conjunction with nonsolvent-induced phase separation (SNIPS) has been increasingly leveraged to fabricate integral-asymmetric membranes. The large number of formulation and processing parameters associated with SNIPS, however, has prevented the reliable construction of high performance membranes. In this study, we apply dynamical self-consistent field theory to model the SNIPS process and investigate the effect of various parameters on the membrane morphology: solvent selectivity, nonsolvent selectivity, initial film composition, and glass transition composition. We examine how solvent selectivity and concentration of polymers in the film impact the structure of micelles that connect to form the membrane matrix. In particular, we find that preserving the order in the surface layer and forming a connection between the supporting and surface layer are nontrivial and sensitive to each parameter studied. The effect of each parameter is discussed, and suggestions are made for successfully fabricating viable block copolymer membranes. [ABSTRACT FROM AUTHOR]

The absolute photoabsorption cross sections of norbornadiene (NBD) and quadricyclane (QC), two isomers with chemical formula C7H8 that are attracting much interest for solar energy storage applications, have been measured from threshold up to 10.8 eV using the Fourier transform spectrometer at the SOLEIL synchrotron radiation facility. The absorption spectrum of NBD exhibits some sharp structure associated with transitions into Rydberg states, superimposed on several broad bands attributable to valence excitations. Sharp structure, although less pronounced, also appears in the absorption spectrum of QC. Assignments have been proposed for some of the absorption bands using calculated vertical transition energies and oscillator strengths for the electronically excited states of NBD and QC. Natural transition orbitals indicate that some of the electronically excited states in NBD have a mixed Rydberg/valence character, whereas the first ten excited singlet states in QC are all predominantly Rydberg in the vertical region. In NBD, a comparison between the vibrational structure observed in the experimental 11B1–11A1 (3sa1 ← 5b1) band and that predicted by Franck–Condon and Herzberg–Teller modeling has necessitated a revision of the band origin and of the vibrational assignments proposed previously. Similar comparisons have encouraged a revision of the adiabatic first ionization energy of NBD. Simulations of the vibrational structure due to excitation from the 5b2 orbital in QC into 3p and 3d Rydberg states have allowed tentative assignments to be proposed for the complex structure observed in the absorption bands between ∼5.4 and 7.0 eV. [ABSTRACT FROM AUTHOR]

Shoulder pain is a complex, prevalent problem that is multifactorial in nature. While there are many potential causes, one common suspect is the rotator cuff musculature. The purpose of the present study was to induce pain in the supraspinatus muscle of healthy subjects and observe the resulting changes in muscle activity. Eight muscles on 23 subjects were assessed using electromyography: anterior, middle, and posterior deltoid; pectoralis major; upper trapezius; latissimus dorsi; serratus anterior; supraspinatus; and infraspinatus. It was hypothesized that the rotator cuff muscles would display reduced activity during pain, and that reductions in activity would remain after the pain had dissipated. Both of the rotator cuff muscles measured did indeed display reduced activity in a majority of the dynamic, isometric, and maximal contractions. Many of those reductions remained after the pain had subsided. [ABSTRACT FROM AUTHOR]

William Attree (1780–1846) came from a prominent family in Brighton, England. He studied medicine at St Thomas' Hospital, London, and there was unwell for nearly 6 months with severe 'spasms' of the hand/arm/chest (1801–1802). Attree qualified Member of the Royal College of Surgeons in 1803 and served as dresser to Sir Astley Paston Cooper (1768–1841). In 1806 Attree is recorded as 'Surgeon and Apothecary' of Prince's street, Westminster. In 1806 Attree's wife died in childbirth and the following year he underwent emergency amputation of the foot in Brighton following a road traffic accident. Attree served as surgeon in the Royal Horse Artillery at Hastings, presumably in a regimental or garrison hospital. He went onto become surgeon to the Sussex County Hospital, Brighton, and Surgeon Extraordinary to two Kings: George IV and William IV. In 1843 Attree was appointed as one of the original 300 Fellows of the Royal College of Surgeons. He died in Sudbury, near Harrow. His son William Hooper Attree (1817–1875) was surgeon to Don Miguel de Braganza, the former King of Portugal. The medical literature appears to lack a history of nineteenth century doctors (especially military surgeons) with physical disability. Attree's biography goes a small way towards developing this field of enquiry. [ABSTRACT FROM AUTHOR]

The substitution of virgin asphalt binder with reclaimed asphalt pavement (RAP) has environmental and economic merits, however, cracking susceptibility arises due to the aged asphalt binder within RAP. The objectives of this study are to (1) enhance the cracking resistance of asphalt mixtures containing 50% RAP utilizing recycling agents (RAs) derived from six petroleum-based and bio-based materials, (2) conduct an environmental impact assessment (represented by global warming potential "GWP") for high-RAP mixtures including RAs, and (3) estimate the cost effectiveness of including high-RAP content in asphalt mixtures. Based on the RAP asphalt binder performance grade (PG), base asphalt binder PG, and RAP content, the RA contents were determined to achieve a target asphalt binder of PG 76-22. A control mixture was benchmarked for comparison, specified for high-traffic volume roads, and contained PG 76-22 polymer-modified asphalt binder. The engineering performance of studied asphalt mixtures was evaluated using the Hamburg wheel-tracking (HWT), semi-circular bend, Illinois flexibility index, Ideal cracking tolerance, and thermal stress-restrained specimen tensile strength tests. It was found that petroleum-derived aromatic oil, soy-based oil, and tall oil fatty acid-based RAs demonstrated a successful restoration of aged RAP asphalt binder without compromising the permanent deformation resistance. The 50% RAP mixtures emitted less GWP by 41% and 42.9% using petroleum- and bio-oil RAs, respectively, and achieved a 31% cost reduction compared to the control mixtures. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to explore the dynamic relationship between formal and non-formal processes of accountability in a public services context. Design/methodology/approach: The paper presents a case study of the impact of the Health and Social Care Act (2012) on the practices of Health and Wellbeing Board (HWB) members. It draws upon multiple data sources, including in-depth interviews with the members, comprehensive archival data published by the HWB (2011–2019), and observations of HWB public meetings. We utilise the concept of dynamic duality (Li, 2008) to further theorise the relationship between formal and non-formal processes of accountability and how they mutually transform one another. Findings: The case illustrates the role of formal and non-formal processes of accountability at a HWB in England. Moreover, the case study reveals the relationship and interaction between the formal and non-formal accountability processes and how they change and transform each other over time. We find that whilst non-formal accountability processes were strengthened by a historical legacy of partnership working, over time the dynamics at play led to the development of formal accountability processes through more sophisticated performance systems, which in turn transformed non-formal accountability processes. Originality/value: The paper presents a more holistic conceptualisation than articulated in prior accountability literature, dynamic duality, on the relationship between formal and non-formal accountability processes. Through application of this conceptualisation to a HWB in England, the paper spotlights the inter-relationship between formal and non-formal processes of accountability, and how they have the potential to transform each over an extended time-period. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to explore if academic training and/or on-the-job experience predicts general health literacy, hearing loss health literacy, and self confidence levels of speech-language pathologists (SLPs). Method: Participants included 423 SLPs with differing levels of academic training and on-the-job experience working with children who are deaf or hard of hearing (DHH). General health literacy, hearing loss health literacy, and confidence levels treating children who are DHH were assessed. Data were analyzed using SPSS, with descriptive statistics, Pearson’s r correlations, and multiple linear regression models. Results: SLPs had high levels of general health literacy but marginal to low levels of hearing loss health literacy. Neither academic training nor on-the-job experience predicted general health literacy, but they were predictive of hearing loss terminology knowledge. Only on-the-job experience predicted in-depth hearing loss content knowledge. There was an interaction of training and experience for confidence of SLPs in treating children who are DHH. SLPs with greater years of experience exhibited lower confidence with an increasing amount of coursework, whereas SLPs with fewer years of experience displayed higher confidence with an increasing amount of coursework. Conclusions: Results indicated that the driving factor for development of indepth hearing loss health literacy in SLPs is on-the-job experience. Methods of integrating experiential learning into academic training should be evaluated. [ABSTRACT FROM AUTHOR]

This article examines the role of the district nurse advanced nurse practitioner and its contribution to the transformation of district nursing services. Primary care is under increasing pressure to bridge the gap between demand and resources, with national and local priorities focusing on frailty and unscheduled care. This article outlines the implementation of the district nurse advanced nurse practitioner role within NHS Greater Glasgow and Clyde and presents findings from a local evaluation. By exploring the impact across the four pillars of advanced practice—clinical practice, research and development, facilitation of learning and leadership—the early findings suggest that this innovative role has had a transformational impact on optimising primary care provision and reducing avoidable hospital admissions for patients on a district nursing caseload. Further research into this role is necessary to ensure that its contribution is comprehensively measured, strengthening the case for recognising this highly skilled role as a key player in NHS Scotland's primary and community health care systems. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ+) individuals are significantly less likely to have a primary health care provider, and are more likely to be uninsured, and postpone medical care. A health care provider's lack of knowledge in LGBTQ+ health needs, low confidence in discussing sexuality, and bias can result in LGBTQ+ patients choosing to delay or avoid seeking care. These are missed opportunities for health care providers to recognize their unique needs, provide education and preventive screenings and care, and manage chronic conditions. Purpose: The aim of this study was to examine nurse practitioner students' perceptions of knowledge, confidence, and experiences related to caring for LGBTQ+ patients. Methodology: Using a descriptive, cross-sectional survey research design, a 29-item online survey was distributed through email to nurse practitioner students (n = 419) across the United States. Results: Overall, nurse practitioners (NP) students demonstrated infrequent questioning related to gender preferences, sexual terms, and clarification of relationships. Results showed that 77.9% of NP students within two terms of graduation had not received any LGBTQ+-specific training. Almost 75% of the NP students reported not routinely asking about sexuality, and 82% reported infrequently or never asking gender identity. Furthermore, 93.1% of respondents reported providers infrequently or never ask about preferred gender or pronouns, and 86% reported providers infrequently inquire about sexual identity in primary care visits. Conclusions: Study findings demonstrate the uniqueness of managing care for LGBTQ+ patients and importance for more detailed LGBTQ+ health training in curricula in NP programs. Implications: Closing the gap in health care for LGBTQ+ patients is paramount in addressing global health disparities and population care. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension in children is progressive with wide variability in prognosis. This document provides an evidence-based clinical practice guideline for the management of children with progressive pulmonary hypertension despite optimal therapy. Methods: A multidisciplinary panel identified pertinent questions regarding the management of children with pulmonary hypertension that has progressed despite optimal therapy, conducted systematic reviews of the relevant literature, and applied the Grading of Recommendations, Assessment, Development and Evaluation approach to develop clinical recommendations. Results: After reviewing the research evidence, the panel considered the balance of desirable (benefits) and undesirable (harms and burdens) effects of the interventions in each proposed question. Valuation of our main outcomes was also considered, together with resources required, equity, acceptability, and feasibility. Recommendations were developed for or against interventional strategies specific to children with pulmonary hypertension that has progressed despite optimal therapy. Conclusions: Although there is a growing population of children with pulmonary hypertension, there is a striking lack of empirical evidence regarding management of those whose disease has progressed despite optimal pharmacotherapy. The panel formulated and provided the rationale for clinical recommendations for or against interventional strategies on the basis of this limited empirical evidence, coupled with expert opinion, to aid clinicians in the management of these complex pediatric patients. In addition, we identified important areas for future research. [ABSTRACT FROM AUTHOR]

Rationale: Serum IgG deficiency is associated with morbidity in chronic obstructive pulmonary disease (COPD), but it is unclear whether concentrations in the lower end of the normal range still confer risk. Objectives: To determine if levels above traditional cutoffs for serum IgG deficiency are associated with exacerbations among current and former smokers with or at risk for COPD. Methods: Former and current smokers in SPIROMICS (the Subpopulations and Intermediate Outcome Measures of COPD study) (n = 1,497) were studied: 1,026 with COPD and 471 at risk for COPD. In a subset (n = 1,031), IgG subclasses were measured. Associations between total IgG or subclasses and prospective exacerbations were evaluated with multivariable models adjusting for demographic characteristics, current smoking, smoking history, FEV1 percent predicted, inhaled corticosteroids, and serum IgA. Measurements and Main Results: The 35th percentile (1,225 mg/dl in this cohort) of IgG was the best cutoff by Akaike information criterion. Below this, there was increased exacerbation risk (incidence rate ratio [IRR], 1.28; 95% confidence interval [CI], 1.08–1.51). Among subclasses, IgG1 and IgG2 below the 35th percentile (354 and 105 mg/dl, respectively) were associated with increased risks of severe exacerbation (IgG1, IRR, 1.39; 95% CI, 1.06–1.84; IgG2, IRR, 1.50; 95% CI, 1.14–1.1.97). These associations remained significant when additionally adjusting for a history of exacerbations. Conclusions: Lower serum IgG is prospectively associated with exacerbations in individuals with or at risk for COPD. Among subclasses, lower IgG1 and IgG2 are prospectively associated with severe exacerbations. The optimal IgG cutoff was substantially higher than traditional cutoffs for deficiency, suggesting that subtle impairment of humoral immunity may be associated with exacerbations. [ABSTRACT FROM AUTHOR]

Background: Cancer-related cognitive impairment (CRCI) is reported by 45% of patients with cancer. Significant gaps in knowledge remain regarding the mechanisms that underlie CRCI. Objectives: Using a data-driven approach, the study purpose was to evaluate for perturbed pathways associated with membership in the High versus the Low CRCI profiles. Methods: Patients completed the Attentional Function Index six times over two cycles of chemotherapy. Using findings from a previous latent profile analysis, subgroups of patients with high versus low levels of CRCI were evaluated (i.e., High versus Low CRCI profiles). Gene expression was quantified using either ribonucleic (RNA)-sequencing or microarray analyses and pathway impact analyses were performed. Signaling pathways were defined using the Kyoto Encyclopedia of Genes and Genomes database. Results: A total of 508 patients had data available for analysis. Of the 261 patients in the RNA-sequencing sample, 48.7% were in the High class and 51.3% were in the Low class. Of the 247 patients the microarray sample, 46.6% were in the High class and 53.4% were in the Low class. Pathway impact analyses identified seven perturbed pathways related to neurotransmission (i.e., glutamatergic synapse, GABAergic synapse, dopaminergic synapse, serotonergic synapse, long-term depression, cholinergic synapse, retrograde endocannabinoid signaling). Conclusions: This study is the first to describe associations between self-reported CRCI in patients receiving chemotherapy for breast, gastrointestinal, gynecological, or lung cancer and seven neurotransmission pathways. These findings provide new insights into potential targets for mechanistically based interventions. [ABSTRACT FROM AUTHOR]

We investigate the question of when an eta quotient is a derivative of a formal power series with integer coefficients and present an analysis in the case of level 10. As a consequence, we establish and classify an infinite number of integral evaluations such as ∫ 0 e - 2 π / 10 q ∏ j = 1 ∞ (1 - q j) 3 (1 - q 10 j) 8 (1 - q 5 j) 7 d q = 1 4 10 - 4 5 - 1. We describe how the results were found and give reasons for why it is reasonable to conjecture that the list is complete for level 10. [ABSTRACT FROM AUTHOR]

This Faraday Discussion was the first to focus on the increasingly central role of big data, machine learning, and artificial intelligence in the chemical sciences. The aim was to critically discuss these topics, and to explore the question of how data can enable new discoveries in chemistry, both now and in the future. The programme spanned computational and experimental work, and encompassed emerging topics such as natural language processing, machine-learned potentials, optimization strategies, and robotics and self-driving laboratories. Here I provide some brief introductory comments on the history of this field, along with some personal views on the discussion topics covered, concluding with three future challenges for this area. [ABSTRACT FROM AUTHOR]

The Faraday Discussions article explores the use of open-source software in academia and the challenges of competing with corporate-funded projects, focusing on the development of Web-BO for predicting anisotropic dielectric tensors in materials. It discusses the potential applications of anisotropic materials in various technologies and their impact on fields like metamaterials and thermoelectrics. The text also addresses data integrity, synthesis, and computational methods in scientific research, emphasizing the importance of high-quality data, proper training, and standardized procedures in both industry and academia, as well as the need for shared best practices and open peer review systems to enhance reproducibility and clarity in research. [Extracted from the article]

Changes in drivers of academic roles within higher education institutions globally have resulted in increased proportions of academics in education focused (EF) posts. International and UK research suggests that EF academics can experience dissatisfaction with career progression and the perceived value of their work, including those in research-intensive universities. Previous UK research was conducted prior to the introduction of the TEF which has altered the landscape. Therefore, it was timely to examine the current experience of EF academics in research-intensive universities through a theoretical lens to understand barriers and facilitators to career progression. This interview-based study used two theoretical frameworks, Feldman and Ng's Framework for Career Mobility, Embeddedness, and Success and Kanter's theory of Power within organisations to explore the experiences of 43 EF academics across 12 research-intensive UK universities. Four contract types were identified, some of which allowed promotion. Three broad themes were derived from the data, including (1) Lack of agreement on the definition of education-focused academic roles, (2) Level of value and appreciation of educational expertise and the impact on education-focused academics, (3) Career development opportunities for education-focused academics. Recommendations to further enhance the experience and career progression for EF academics in research-intensive universities further include; ensuring transparency in recruitment into EF posts as to whether career development is possible within that post, the need to continue the sector-wide discussion on the definition of EF roles that recognises the complexity and diversity of activity and continued work to value and recognise appropriately educational expertise. [ABSTRACT FROM AUTHOR]

Objective To detect and classify features of stigmatizing and biased language in intensive care electronic health records (EHRs) using natural language processing techniques. Materials and Methods We first created a lexicon and regular expression lists from literature-driven stem words for linguistic features of stigmatizing patient labels, doubt markers, and scare quotes within EHRs. The lexicon was further extended using Word2Vec and GPT 3.5, and refined through human evaluation. These lexicons were used to search for matches across 18 million sentences from the de-identified Medical Information Mart for Intensive Care-III (MIMIC-III) dataset. For each linguistic bias feature, 1000 sentence matches were sampled, labeled by expert clinical and public health annotators, and used to supervised learning classifiers. Results Lexicon development from expanded literature stem-word lists resulted in a doubt marker lexicon containing 58 expressions, and a stigmatizing labels lexicon containing 127 expressions. Classifiers for doubt markers and stigmatizing labels had the highest performance, with macro F 1-scores of 0.84 and 0.79, positive-label recall and precision values ranging from 0.71 to 0.86, and accuracies aligning closely with human annotator agreement (0.87). Discussion This study demonstrated the feasibility of supervised classifiers in automatically identifying stigmatizing labels and doubt markers in medical text and identified trends in stigmatizing language use in an EHR setting. Additional labeled data may help improve lower scare quote model performance. Conclusions Classifiers developed in this study showed high model performance and can be applied to identify patterns and target interventions to reduce stigmatizing labels and doubt markers in healthcare systems. [ABSTRACT FROM AUTHOR]

Objective Event capture in clinical trials is resource-intensive, and electronic medical records (EMRs) offer a potential solution. This study develops algorithms for EMR-based death and hospitalization capture and compares them with traditional event capture methods. Materials and Methods We compared the effectiveness of EMR-based event capture and site-captured events adjudicated by a clinical endpoint committee in the multi-center INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure (INVESTED) trial for participants from the Veterans Affairs healthcare system. Varying time windows around event dates were used to optimize events matching. The algorithms were externally validated for heart failure hospitalizations in the Medical Information Mart for Intensive Care (MIMIC)-IV database. Results We observed 100% sensitivity for death events with a 1-day window. Sensitivity for cardiovascular, heart failure, pulmonary, and nonspecific cardiopulmonary hospitalizations using discharge diagnosis codes varied between 75% and 95%. Including Centers for Medicare & Medicaid Services data improved sensitivity with no meaningful decrease in specificity. The MIMIC-IV analysis showed 82% sensitivity and 99% specificity for heart failure hospitalizations. Discussion EMR-based method accurately identifies all-cause mortality and demonstrates high accuracy for cardiopulmonary hospitalizations. This study underscores the importance of optimal time windows, data completeness, and domain variability in EMR systems. Conclusion EMR-based methods are effective strategies for capturing death and hospitalizations in clinical trials; however, their effectiveness may be influenced by the complexity of events and domain variability across different EMR systems. Nonetheless, EMR-based methods can serve as a valuable complement to traditional methods. [ABSTRACT FROM AUTHOR]

Henry Kipping (1726–1785) was an apothecary and surgeon in Brighton, England. Here we present a series of contemporary references to Kipping from newspaper, book, archive and web-based resources. Some relate to his medical practice (resuscitating a 'drowned' elderly physician and a fisherman, bleeding a member of parliament who had fallen from his horse and praising a nostrum for the 'gravel and stone'). Social references include a duel with an army officer whose sword Kipping confiscated. Kipping appears to have been popular, connected with members of Brighton's high society and passionate about traditional past times, e.g. swordsmanship, horse riding and hunting on the Sussex downs. Indeed, Kipping's horse ran in the earliest known horse race in Brighton (1770). He was consulted by notable local residents including the Thrale family of Brighton and Lady Wilhelmina Shelley (the latter evidenced by Kipping partaking in her funeral procession in 1772). Kipping lived and practised at 28 West street, a road most famous for its (now lost) George Inn where King Charles II stayed just prior to his escape to Normandy. Kipping comes across as a colourful and eccentric clinician. [ABSTRACT FROM AUTHOR]

Young South Africans regularly generate livelihoods on the move, as they morph across a mainstream economic field and two translocal sub-fields. While a field implies sets of relations operating under common conditions, translocal sub-fields are local spaces of exchange and practice, where resources are utilised, in a relationship with other linked spaces. In South Africa, the mainstream economic field largely consists of an urban labour market with some good jobs and unskilled labour. Alongside it a rural sub-field consists of farm and off-farm activities, reciprocal exchange and state grants. Finally, on the outskirts of urban areas a township sub-field consists of young people hustling resources in the informal sector. After describing how mobile young South Africans make a living across these spaces, I show how this case is both similar and different to other post-colonial contexts with substantial informal economic sectors like India and Brazil. In these places, youth strive to make a living by accumulating resources as they move across spaces that include, but transcend, the labour market. A particular form of mobile, global South youth livelihood generation occurs across the mainstream capitalist economy and informal urban and rural contexts, where economic relations remain largely embedded in social life. [ABSTRACT FROM AUTHOR]

With health equity growing as a priority within health care, health systems must transform that calling into action within their social, economic, and political environments. The current literature has not compared how different organizations manage the same health disparities intervention. This qualitative study aims to illustrate how different organizations navigated the implementation and sustainability of a hypertension disparities intervention by comparing experiences across Federally Qualified Health Centers (FQHCs), a private health system, and other non-clinical partnering organizations. As a study within a randomized controlled trial designed to reduce disparities in hypertension care, we conducted interviews with health care leaders before and after participation in the trial's multi-level intervention. Before participation, we interviewed five health care leaders representing five health systems. Following the intervention, we interviewed 14 leaders representing the five health systems and two partnering organizations. Discussions focused on intervention implementation and plans for sustainability. The primary considerations in implementation were appropriate staffing and multi-level organizational buy-in. When discussing long-term planning, health systems prioritized the structure of a stepped-care protocol incorporating community health workers (CHWs) and case managers. The sustainability of the CHW intervention at FQHCs was dependent on funding, whereas a private, non-FQHC physician practice network focused on expanding current resources for more patients. These findings serve as anticipatory guidance for organizations aiming to reduce hypertension disparities and provide support for policies that financially assist these interventions. Further investigation is warranted on the organizational factors that may influence the degree of success in eliminating health care disparities. [ABSTRACT FROM AUTHOR]

Investigation and management of hypotonic polyuria is a common challenge in clinical endocrinology. The 3 main causes, recently renamed to arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus), arginine vasopressin resistance (AVP-R, formerly nephrogenic diabetes insipidus), and primary polydipsia (PP) require accurate diagnosis, as management differs for each. This new nomenclature more accurately reflects pathophysiology and has now been adopted by the Systemized Nomenclature of Medicine (SNOMED). Advances in diagnosis over the last few years have centered around the use of copeptin measurement. Here, we use 3 patient case histories to highlight the use of this approach, and to demonstrate how it can succeed where other approaches, such as the water deprivation test, sometimes fail. We discuss the overall approach to each type of patient and the strengths and limitations of diagnostic strategies, illustrating the use of the new nomenclature. [ABSTRACT FROM AUTHOR]

The document explores inter-racial genetic differences in myelofibrosis, focusing on a diverse inner-city center analysis. The study conducted at Montefiore Medical Center in the Bronx, NY, with a predominantly Hispanic and Black population, aimed to identify high-risk mutations and their impact on clinical outcomes in a multi-ethnic cohort. Findings revealed higher prevalence of high molecular risk mutations in non-White patients, particularly Black and Hispanic cohorts, but no significant differences in leukemic transformation or overall survival between racial groups. The study highlights the importance of validating mutational risk profiles in diverse populations and calls for further investigation with larger-scale studies. [Extracted from the article]

Depression is common among people living with HCV and HIV, which contributes to health services utilization (HSU). It is unknown whether successful HCV treatment affects this. We examined depressive symptoms and HSU in people co-infected with HIV-HCV and their association with sustained virologic response (SVR) during the direct-acting antiviral era. We predicted depressive symptoms by a random forest classifier in the Canadian Co-infection Cohort. HSU was measured by inpatient and out-patient visits in the previous six months. We fit zero-inflated negative binomial models. Of the 1153 HCV RNA+participants, 530 were treated and of them, 95% achieved SVR. Without SVR, inpatient and out-patient visits were 17% and 5% higher among those with depressive symptoms than those without respectively; with SVR, this association disappeared. SVR was associated with 24% fewer inpatient visits. Thus, depressive symptoms were associated with a modest increase in HSU, and SVR appears to attenuate this effect. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate return to activity following flatfoot reconstruction with lateral column lengthening (LCL) by assessing functional postoperative data and identifying patient characteristics associated with poor function following surgery. Methods: Consecutive patients that underwent operative flatfoot correction including LCL and other necessary procedures from 2014 to 2019 by 3 fellowship trained foot and ankle orthopedic surgeons were retrospectively administered Foot and Ankle Ability Measure (FAAM) Activities of Daily Living (ADL) and FAAM Sports questionnaires with no preoperative scoring available. Patient demographic factors, comorbidities, and radiographic features were evaluated as predictors of outcome scores to simulate return to activity. Statistical analysis, including student's t-tests and analysis of variance, was performed. Results: A total of 54 patients were included. A body mass index (BMI) of 30 kg/m2 or greater was associated with a lower ADL score (P =.002) and Sports score (P =.002). Preoperative hindfoot valgus of 9° or higher was associated with higher ADL scores (P =.040). Neither age nor any flatfoot radiographic parameters yielded significant differences in functional scores. Conclusion: This study demonstrated relatively high average FAAM scores in both the ADL and the sports subscales, consistent with previous studies. This study also identified lower BMI and greater preoperative hindfoot valgus as potential predictors of improved functional outcome following reconstruction. Level of Evidence: Level III: Retrospective case control [ABSTRACT FROM AUTHOR]

Objective: The present exploratory study uses a longitudinal design to assess the associations between electronic cigarette (e-cigarette) use and cigarette smoking, motivation to quit and trait impulsivity among adult smokers. Methods: One hundred and sixteen cigarette smokers only and ninety-one dual users (smoke cigarettes and use e-cigarettes) were recruited (mean age [standard deviation] = 25.11[6.94], male = 48.3%). Participants were recruited online and 121 were followed-up at 3 months. Participants completed online questionnaires regarding socio-demographics, smoking/e-cigarette use characteristics and trait impulsivity at baseline, and they self-reported their smoking status at 3-month follow-up. Results: The use of e-cigarettes in cigarette smokers was associated with a higher rate of stopping cigarette smoking at follow-up, relative to smokers who did not use e-cigarettes (χ2[1] = 11.03, p < 0.01). Multivariate logistic regressions controlling for age and gender showed a significant association between motivation to quit and stopping cigarette smoking at follow-up (odds ratio = 2.11, 99% Confidence Interval = 1.12–3.97, p < 0.01). There was no link between trait impulsivity and stopping cigarette smoking. Conclusions: The data suggest that e-cigarettes may increase rates of quitting cigarette smoking. [ABSTRACT FROM AUTHOR]

Background: The Stress Hyperglycemia Ratio (SHR), a new biomarker calculated from glucose and HbA1c levels, has been linked to significant clinical outcomes in diabetes. This study investigates the potential of the SHR to predict End‐Stage Renal Disease (ESRD) among patients with Diabetic Kidney Disease (DKD). Methods: We included 316 participants from the West China Hospital T2DM‐DKD cohort (January 2008–September 2020), divided into three SHR tertiles: T1 (SHR <0.7), T2 (SHR ≥0.7 to <0.94) and T3 (SHR ≥0.94). A second retrospective cohort of 625 DKD patients was recruited from Sichuan University Hospital (January 2019–May 2022), with similar inclusion criteria. SHR was analysed using Restricted Cubic Spline, Kaplan–Meier curves and Cox proportional hazards models. Key confounders such as eGFR, proteinuria, hypoalbuminemia and glucose‐lowering medications were adjusted for in the analysis. Results: In Cohort 1 (median follow‐up 42 months), 38.6% developed ESRD. Kaplan–Meier curves showed a higher incidence of ESRD in the lowest and highest SHR tertiles compared to the middle group (p < 0.01). Multivariate analysis confirmed that SHR <0.7 (HR 1.71, 95% CI: 1.01–2.90) and SHR ≥0.94 (HR 1.93, 95% CI: 1.16–3.20) were significantly associated with ESRD. In Cohort 2 (median follow‐up 18.6 months), patients with SHR <0.7 and ≥0.94 had significantly higher risks of ≥30% eGFR decline or ESRD, with adjusted HRs of 2.18 (95% CI: 1.15–4.11) and 2.68 (95% CI: 1.38–5.23), respectively. Conclusion: This study observed a U‐shaped relationship between SHR and ESRD in patients with DKD. Both very high and very low SHR values correlate with increased risks, highlighting the critical importance of glucose management in chronic diabetes care. [ABSTRACT FROM AUTHOR]

Anal high‐risk human papillomavirus (HRHPV) testing‐based anal cancer screening gay and bisexual men (GBM) is associated with high sensitivity, but low specificity. We report the potential role of triage use of anal cytology with HRHPV testing in detecting 12‐month persistent anal high‐grade squamous epithelial lesions (HSIL) in a cohort of GBM in Sydney, Australia. Participants were GBM from the Study of the Prevention of Anal Cancer (SPANC) who underwent annual anal HPV testing, cytology, and high‐resolution anoscopy (HRA)‐guided histology. The sensitivity and specificity of five screening algorithms based on HRHPV test results with triage use of anal cytology (atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells, cannot exclude HSIL (ASC‐H) used as referral thresholds) were compared to these of HRHPV testing and anal cytology alone. A total of 475 men who had valid HRHPV, cytological, and histological results at both baseline and first annual follow‐up visits were included, median age 49 years (inter‐quartile range: 43–56) and 173 (36.4%) GBM with human immunodeficiency virus. Of all triage algorithms assessed, two had comparable sensitivity with HRHPV testing alone in detecting persistent anal HSIL, but ~20% higher specificity and 20% lower HRA referral rates. These two algorithms involved the immediate referral of those with HPV16 and for those with non‐16 HRHPV either immediate or delayed (for 12 months) referral, depending on cytology result at baseline. Triage use of anal cytology in GBM testing positive for anal HRHPV increases specificity and reduces referral rates while maintaining high sensitivity in detection of HSIL. [ABSTRACT FROM AUTHOR]

Background: Elevated renin has been shown to predict poor response to standard vasoactive therapies and is associated with poor outcomes in adults. Similarly, elevated renin was associated with mortality in children with septic shock. Renin concentration profiles after pediatric cardiac surgery are unknown. The purpose of this study was to characterize renin kinetics after pediatric cardiac surgery. Methods: Single-center retrospective study of infants who underwent cardiac surgery with cardiopulmonary bypass (CPB) utilizing serum samples obtained in the perioperative period to measure plasma renin concentrations (pg/mL). Time points included pre-bypass and 1, 4, and 24 h after initiation of CPB. Results: Fifty patients (65% male) with a median age 5 months (interquartile range (IQR) 3.5, 6.5) were included. Renin concentrations peaked 4 h after CPB. There was a significant difference in preoperative and 4 h post-CPB renin concentration (4 h post-CPB vs preoperative: mean difference 100.6, 95% confidence interval (CI) 48.9-152.4, P <.001). Median renin concentration at 24 h after CPB was lower than the preoperative baseline. Conclusions: We describe renin kinetics in infants after CPB. Future studies based on these data can now be performed to evaluate the associations of elevated renin concentrations with adverse outcomes. [ABSTRACT FROM AUTHOR]

Breastfeeding theoretical and skills training is important for health care professionals engaging with the mother infant dyad to increase breastfeeding exclusivity and duration. The aim of this study was to evaluate the knowledge, attitudes and practices (KAPs) of health care professionals following completion of a university professional graduate programme in breastfeeding and lactation. A pre and post—educational study design was used. All students enrolled in a six month programme were invited to complete an online anonymous survey at two time points: January 2023 and July 2023. Ethical approval (LS-C-23-17) was obtained in January 2023. Descriptive statistics were utilised to report percentages and means, and independent T tests were used to report mean differences between variables on knowledge, attitude and practices. All students completed the module. The pre survey participant response rate was n = 55 (92.82%) and the post survey participant response rate n = 33 (60%). Comparison of the pre and post questionnaire report nine statistically significant results following completion of the university breastfeeding and lactation programme. Knowledge scores increased specifically with higher mean knowledge scores for reporting "I am confident with my knowledge about breastfeeding" and statistically significant mean difference of 0.29 following completion of the module (95% CI, 0.13 to 0.45) (t (64) = 3.59, p = 0.001). The programme evaluation identifies the importance of a professional graduate breastfeeding and lactation education programme for interdisciplinary health care professionals increasing knowledge, attitudes and practices and ultimately increasing breastfeeding rates in the short and long term, with improved maternal and child health outcomes. [ABSTRACT FROM AUTHOR]

Platelets are enriched in miRNAs and harbor Ago2 as the principal RNA silencing Argonaute. However, roles in thrombopoiesis and platelet function remain poorly understood. We generated megakaryocyte/platelet-specific Ago2-deleted (Ago2 KO) mice and assessed proteomic and functional effects. We predicted platelet hyperreactivity with Ago2 deletion due to large-scale upregulated protein expression. Platelet counts were normal. Mean volumes were increased, associated with larger, though fewer megakaryocytes. Ago2-deleted platelets from male mice showed hyperreactivity to thromboxane but not to other agonists compared to controls, whereas Ago2-deleted platelets from female mice showed normal reactivity. Ago2 KO mice displayed normal hemostasis and clot dynamics. Proteomes of Ago2-deleted and wild type platelets were mostly similar. However, Ago1 - undetectable in wild type platelets - was upregulated in Ago2-deleted platelets in both males and females, confirmed by immunoblotting. Female Ago2-deleted platelets selectively showed downregulation of a protein cohort established in breast cancer cells to be transcriptionally regulated by estrogen receptor-beta coupled to Ago2, whereas male Ago2-deleted platelets did not. Thus, Ago2 is important for platelet development and function, putatively partially rescued by upregulation of Ago1. Platelet reactivity controlled by Ago2 reflects sex-specific regulation of gene expression potentially at both transcriptional and translational levels in megakaryocytes and platelets. [ABSTRACT FROM AUTHOR]

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters allele expression commitment, in support of two proposed mechanisms5,6 for the regulation of aRMAE. We tested peripheral blood mononuclear cells from individuals with IEIs with shared genetic lesions but discordant clinical phenotypes for aRMAE. Among two relatives who were heterozygous for a mutation in PLCG2 (delEx19), an antibody deficiency phenotype corresponds to selective mutant allele expression in B cells. By contrast, among relatives who were heterozygous for a mutation in JAK1 (c.2099G>A; p.S700N), the unaffected carrier T cells predominantly expressed the wild-type JAK1 allele, whereas the affected carrier T cells exhibited biallelic expression. Allelic expression bias was also documented in phenotypically discordant family members with mutations in STAT1 and CARD11. This study highlights the importance of considering both the genotype and the 'transcriptotype' in analyses of the penetrance and expressivity of monogenic disorders. Somatically determined preferential allelic expression of select genes that when mutated cause inborn errors of immunity corresponds with disease phenotypes, suggesting that the penetrance and expressivity of monogenic disorders is also dependent on the 'transcriptotype'. [ABSTRACT FROM AUTHOR]